Dư C Lý Lâm Sàng

ANTIBIOTIC BASIC FOR CLINIC 2nd
ANTIBIOTIC BASIC FOR CLINIC THE ABCs OF CHOOSING THE RIGHT

ANTIBACTERIAL AGENT 2nd Alan R. Hauser (2013)
Mc lc
PHN I: CC KIN THC C BN V VI KHUN ............................................ 3
Chng 1: Mng t bo ........................................................................................... 3
Chng 2: Sn xut protein ..................................................................................... 5
Chng 3: Sinh sn.................................................................................................. 8
Chng 4: Xc nh nhy cm ca vi khun vi khng sinh ........................... 12
PHN II: CC TC NHN KHNG KHUN ...................................................... 14
Chng 5: Khng sinh tc dng ln thnh ca t bo ........................................... 14
Chng 6: Khng sinh bt hot s sn xut protein.............................................. 48
Chng 7: Khng sinh tc ng ti ADN v s sao chp..................................... 73
Chng 8. Tc nhn khng Mycobacterium ......................................................... 83
Chng 9: Tng hp ngn v cc khng sinh ....................................................... 86
PHN III. IU TR C HIU ............................................................................ 90
Chng 10- Vi khun gram dng........................................................................ 90
Chng 11. Vi khun gram m ........................................................................... 106
Chng 12: Vi khun k kh ............................................................................... 124
Chng 13. Vi khun khng in hnh ............................................................... 130
Chng 14: Xon khun ...................................................................................... 137
PHN IV. IU TR KINH NGHIM .................................................................. 143
Chng 15: Mycobacteria ................................................................................... 143
Chng 16. Vim Phi ........................................................................................ 147
Chng 17 Nhim trng ng tit niu............................................................. 157
Chng 18. Bnh vim vng chu ...................................................................... 161
Chng 19: Vim mng no................................................................................ 164
Chng 20. Vim m t bo ................................................................................ 169
Chng 21: Vim tai gia .................................................................................. 172
Chng 22: Vim ni tm mc nhim khun ...................................................... 174
Chng 23. Nhim khun lin quan n catheter trong lng mch .................... 181
Chng 24: Nhim trng bng ......................................................................... 184
PHN V. CA LM SNG ..................................................................................... 187
Ca lm sng 1....................................................................................................... 187
Ca lm sng 2....................................................................................................... 189
Ca lm sng 3....................................................................................................... 191
Ca lm sng 4....................................................................................................... 192
Ca lm sng 5....................................................................................................... 192
Ca lm sng 6....................................................................................................... 194
Ca lm sng 7....................................................................................................... 195
Ca lm sng 8....................................................................................................... 196
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Ca lm sng 9 ....................................................................................................... 196
Ca lm sng 10 ..................................................................................................... 197
Ca lm sng 11 ..................................................................................................... 198
Ca lm sng 12 ..................................................................................................... 198
PHN VI. HI V TR LI ................................................................................. 201
PHN VI. PH LC............................................................................................... 217
Ph lc 1. Liu khng sinh ngi trng thnh ............................................... 217
Ph lc 2: Liu khng sinh s dng tr em....................................................... 223
Ph lc 3. Liu khng sinh ngi trng thnh suy gim chc nng thn ...... 229
Ph lc 4. Khng sinh trong thai k ..................................................................... 238
Ph lc 5- Thuc gc v bit dc cc khng sinh thng dng .......................... 243
Ph lc 6. iu tr nhim trng do vi khun nhm khng b sinh hc gy ra .... 246
Ph lc 7. Ti liu tham kho y khoa................................................................... 247
Ph lc 8. Ti liu tham kho vn hc ................................................................. 248
Ph lc 9. Tr li cu hi ca mi chng .......................................................... 249
PHN I: CC KIN THC C BN V VI KHUN
Chng 1: Mng t bo
Dch: DS. Nguyn Quang Vit, Cu sinh vin dc H Dc HN
Hiu nh: DS. V Th H
Mng t bo l lp o gip bo v bao quanh vi khun v cho php chng tn ti trong mi trng
a dng v khc nghit. Mng t bo mt s vi khun bao gm mng sinh cht hay mng t bo
cht (cytoplasmic membrane) bao quanh bi mt li bn chc v khng linh ng gi l vch t
bo (cell wall) hay thnh t bo (Hnh 1-1.); cc vi khun ny gi l vi khun gram dng. Ngc
li, mng t bo ca vi khun gram m bao gm mng t bo cht bao quanh mt vch t bo
mng c bao quanh lp mng lipid th hai gi l mng ngoi (outer membrane). Mng ngoi
gm nhiu phn t lipopolysaccharid (LPS), phn t ny rt c hi i vi con ngi. Khong
trng gia mng ngoi v mng t bo cht c thnh t bo gi l khng gian periplasmic hoc
periplasm. D vi khun gram dng hay gram m thng c th xc nh c theo k thut
nhum gram, vi khun gram dng bt mu xanh hoc tm cn vi khun gram m bt mu hng.
Nhum gram thng l bc u tin phng th nghim vi sinh bnh vin s dng xc nh mt
loi vi khun cha c bit t mt mu lm sng.
Ging nh cc t bo ca con ngi, mng t bo cht ngn cc ion i vo hoc ra khi chnh cc
t bo , gi cho t bo cht v cc thnh phn vi khun vi nh dng xc nh. Vch t bo l
lp bn chc gip cho vi khun c hnh dng c trng v bo v vi khun khi tc ng c hc v
thm thu. vi khun gram m, mng ngoi ng vai tr nh mt hng ro bo v b sung v
ngn nga nhiu cht xm nhp vo vi khun.Tuy nhin, lp ny cng cha cc knh, gi l cc
porin cho php mt s hp cht nh cc phn t c s dng trong qu trnh chuyn ha ca vi
khun i qua.
Do cc t bo ca con ngi khng c thnh t bo, cu trc ny l mt mc tiu l tng cho cc
tc nhn khng khun. nh gi cch cc tc nhn ny lm vic, u tin chng ta phi hiu
c cu trc ca thnh t bo. Phc hp phc tp ny do mt cht gi l peptidoglycan to thnh,
bn thn cht gm cc polyme ng mch di. Cc polyme lp li hai cht ng: TV-
Acetylglucosamin v AT-acetyl-muramic acid (Hnh 1-2.). Nu thnh t bo bao gm ch ring
cc polyme s l kh yu. Tuy nhin, chui bn peptid m rng t cc loi ng trong polyme v
to thnh cc lin kt cho, mt peptid vi mt peptid khc. Nhng lin kt cho tng bn vng
ng k thnh t bo, cng nh lin kt ngang ca cc vng kim loi tng bn o gip st c
cc hip s thi trung c s dng.
Cc lin kt ngang peptidoglycan c iu ha bi cc enzym ca vi khun, gi l protein gn
penicilin (Penicillin-Binding Protein-PBP) lm trung gian. (L do dng thut ng ny s c
lm r trong chng sau). Nhng enzym ny nhn ra hai acid amin cui ca cc chui peptid bn,
thng l D-alanin-D-alanin v trc tip lin kt cho cc acid amin ny vi mt chui peptid th
hai hoc gin tip qua hnh thnh mt cu d glycin gia hai chui peptid bn.
S hnh thnh vch t bo c cc lin kt cho bn vng gip vi khun c hnh dng c trng. V
d, mt s vi khun hnh que c hnh dng gi l trc khun (bacilli), hnh cu l cu khun
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(cocci), hnh thi trung gian gia trc khun v cu khun c (coccobacilli), cui cng, xon
khun (spirochete) c hnh dng xon c.
Hnh 1-1. Cu trc mng t bo vi khun
Hnh 1-2. Cu trc peptidoglycan. Tng hp peptidoglycan cn lin kt cho cc polyme

di-saccharid do protein gn penicilin (PBP), NAMA (N-Acetylmuramic acid-NAM),
NAGA (N-Acetylglucosamin-NAG), GGG cc cu ni glycin.
CU HI (li gii xem Ph lc 9)

1. Thnh t bo vi khun gm ------------------------
2. ------------------------l cc enzym gip hnh thnh lin kt cho gia cc polyme peptidoglycan.
3. ------------------------l nhng vi khun hnh que.
Chng 2: Sn xut protein

Hiu nh: DS. V Th H
Ging nh tt c cc i qun xm lc, vi khun gy bnh cn phi c tip t. Chng cn cc

ngun lc thch hp thay th cc phn b mn c khng s dng c na v to ra cc vi
khun mi. Vi khun yu cu nhng ngun lc t cc quc gia m chng ang xm chim,
trong trng hp ny chnh l c th con ngi. Trong mt lng ln cc phn cn tng hp
thay th l cc protein. Qu trnh tng hp cc protein ny t c nh s dng cc qu trnh
chung tng t nh cc t bo ca con ngi s dng (Hnh. 2-1). u tin, cc nguyn liu, cc
khi vt liu ti to (building block) nh cc RNA, cc acid amin v phn t giu nng lng c
cha triphosphate nucleoside, phi ginh c v c sn trong vi khun. Nu iu kin ny p
ng, cc gen mu vi khun phin m thnh RNA do cc enzym c bit ca vi khun. Sau
RNA c dch m thnh protein. Do mt s thnh phn m vi khun cn cho cc qu trnh ny
khc ng k so vi qu trnh tng t t bo con ngi, qu trnh sn xut protein ny vi
khun b thuc khng sinh c ch.
NGUYN LIU TH
Hnh 2-1. Tng quan qu trnh sn xut protein trong vi khun.

Hnh 2-2. Cu trc ca ribosome ca vi khun.
Qu trnh tng hp cc protein mi i hi mt lng di do cc khi vt liu ti to cng nh

nng lng. V d, ngi ta c tnh rng nng lng ca ba hoc bn triphosphat nucleoside (v
d, adenosin triphosphat-ATP hay guanosin triphosphat-GTP) l cn thit gn thm mt acid
amin n vo chui protein ang hnh thnh. Vi khun to ra cc vt liu th v nng lng ny
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nh ly ngun nhin liu l glucose t mi trng v x l chng thng qua cc con ng
chuyn ha sn sinh ranng lng v to ra cc hp cht trung gian.
Nhng con ng chuyn ha ny kh phc tp v c s khc bit ng k gia cc t bo vi
khun v cc t bo ca ngi. Chng c th c s dng mt cch hiu qu phn chia vi
khun thnh hai loi: hiu kh v k kh. Vi khun hiu kh s dng oxy t mi trng trong qu
trnh chuyn ha, trong khi vi khun k kh khng s dng. Trong thc t, vi khun k kh nghim
ngt u b oxy git cht bi v chng thiu cc enzym gii c mt s cc sn phm ph c hi
ca oxy, nh hydrogen peroxid v cc gc super-oxid. Mycobacterium tuberculosis l mt v d
v vi khun hiu kh nghim ngt; vi khun k kh nghim ngt bao gm Clostridium difficile v
Bacteroides fragilis. Nhiu vi khun c cc qu trnh chuyn ha cho php chng s dng oxy khi
c hin din ca oxy nhng c th vn hnh nh vi khun k kh khi khng c oxy. Nhng vi
khun ny c gi l ty nghi (falcutative) lin quan n s dng oxy v d nhin l chng tn
ti tt d cho c hay khng c oxy. V d v cc vi khun tu nghi nh vy c Escherichia coli v
Staphylococcus aureus. Cc vi khun khc pht trin tt nht khi c mt lng nh kh oxy, t
hn lng oxy tm thy trong khng kh. Nhng vi khun ny c cho l vi hiu kh (micro-
aerophilic). Campylobacter jejuni l mt v d ca mt loi vi khun vi hiu kh.
Nng lng c sn tiu th bi vi khun c sn sinh v lu tr di dng triphosphate
nucleoside, v trong mt s trng hp di dng chnh lch gradient proton gia trong v ngoi
t bo. Cc dng nng lng tim nng lu tr di dng gradient ny c gi l ng lc
proton. Do proton di chuyn t gradient cao xung thp (t bn ngoi vi khun vo bn trong vi
khun) v xuyn qua mng t bo cht, dng nng lng ny c s dng cung cp nng
lng cho cc qu trnh quan trng nh vn chuyn tch cc nhng cht dinh dng vo t bo v
to ra cc ATP.
PHIN M
Phin m l qu trnh trong cc thng tin cha trong DNA ca mt gen vi khun c s dng
tng hp mt phn t RNA gi l RNA thng tin (mRNA). Cng ging nh cc t bo ca
ngi, phc hp enzym RNA polymerase c vi khun s dng thc hin iu ny. RNA
polymerase gn vo DNA v s dng nh khun mu lin tc gn thm cc acid ribonucleic
vo mt phn t mRNA tng ng. Qu trnh ny l kh hiu qu; iu kin l tng, RNA
polymerase vi khun c th to mt mRNA vi tc 55 nucleotide mi giy.
Mc d c hai phn t thc hin cc chc nng tng t, RNA polymerase vi khun kh khc bit
vi RNA polymerase ca TB c nhn in hnh (nh t bo ngi). (cc TB c nhn in hnh
khng ging nh vi khun, l nhng sinh vt c cha cc ht nhn v cc bo quan c mng ring
trong cc t bo. V d nh t bo cc loi ng vt, thc vt, nm v ng vt nguyn sinh.) V
mt cu trc, RNA polymerase vi khun bao gm nm n v nh v c kch thc tng th
khong 90 x 90 x 160 angstrom, trong khi RNA polymerase ca nm men c nhiu tiu n v hn
v c kch thc 140 x 136 x 110 angstrom. Khc bit chc nng cng tn ti. V d, trong khi
RNA polymerase vi khun chnh n bt u sao chp, RNA polymerase ca TB c nhn
in hnh i hi c tc ng ca cc yu t phin m b sung. Tm quan trng ca phin m i
vi sc khe ca vi khun v s khc bit gia RNA polymerase ca vi khun v RNA
polymerase ca TB c nhn in hnh lm cho phc hp enzym ny l mt mc tiu l tng cho
cc hp cht khng khun.
DCH M
C TB c nhn in hnh v vi khun, cc cu trc i phn t l ribosome u thc hin cng

vic tng hp protein t cc thng tin cha trong mRNA thng qua mt qu trnh gi l dch m.
Nhng phc hp ln ny gm c ribosome RNA (rRNA) v cc protein. Tuy nhin ribosome ca
vi khun c khc bit ng k so vi ribosome ca TB c nhn in hnh. Ribosome 70S ca vi
khun c to ra t mt tiu n v 50S v 30S (Hnh. 2-2). (S l vit tt ca n v Svedberg,
n v o tc lng o bng mt my siu li tm Ultracentrifuge. n v Svedberg, do , phn
nh kch thc ca mt phc hp ch khng phi n thun l php cng). Nhng tiu n v ny
cng c cu trc phc tp. V d cc tiu n v 50S to ra t 2 phn t rRNA v 34 protein, trong
khi cc tiu n v 30S bao gm 1 phn t rRNA v 21 protein. Ngc li, cc ribosome ca TB
c nhn in hnh 80S v kch thc v bao gm mt tiu n v 60S v mt tiu n v 40S. Mi
tiu n v li gm nhiu phn t rRNA v protein.
Cc ribosome hon chnh vn hnh cng vi mt loi RNA khc gi l RNA vn chuyn (tRNA)
sn xut protein mi. Ribosome gn vo v c thng tin trn khun mu mRNA v kt hp
cc acid amin ph hp c cc tRNA vn chuyn gn vo protein ang hnh thnh da trn cc
thng tin trong mu mRNA. Tm quan trng ca dch m c th hin thc t mt na qu
trnh tng hp RNA mt vi khun pht trin nhanh chng l tng hp rRNA v tRNA. Vic tng
hp protein trong vi khun ng vai tr quan trng vi khun pht trin v tnh cht khng ging
nhau gi ribosom ca con ngi v vi khun khin cho ribosome ca vi khun l mt mc tiu hp
dn cho cc khng sinh tc ng. Tht vy, nhiu nhm cc tc nhn khng khun hot ng theo
c ch gn vo v c ch ribosome ca vi khun.
CU HI
1.Vi khun ------------------------ l nhng vi khun ln ln trong mi trng thiu oxy.
2. ------------------------ l mt phc hp enzym to ra mRNA t mt khun mu DNA.
3. Ribosome 70S ca vi khun gm tiu n v ------------------------ v ------------------------, v cc
tiu n v ny li cu to gm ------------------------ v ------------------------
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Chng 3: Sinh sn
Hiu nh: DS. V Th H
Trong cuc chin gia cc vi khun v cc p ng min dch ca con ngi, s lng rt quan
trng. Vi khun lin tc nhn ln n lc p o kh nng phng th ca vt ch v cc yu t
min dch ang khng ngng c gng tiu dit nhng k xm lng. Cn bng ny thng
nghing v p ng min dch ca con ngi nh thuc khng sinh.
Mt v d minh ha ni ln tm quan trng v s nhn ln ca vi khun l ly nhim bnh l trc
khun. Bnh tiu chy ly nhim ny do trc khun l Shigella gy ra v c th xy ra ch sau khi
ung phi khong 200 c th trc khun. Tuy nhin trong mt thi gian ngn, 200 vi sinh vt ny
gy ra tiu chy, trong hng t vi khun b tng ra trong phn mi ngy. R rng vi khun nhn
ln nhanh chng l iu quan trng i vi bnh ny.
Vi khun nhn ln xy ra do s sinh sn nh phn, l qu trnh mt vi khun m phn chia thnh
hai t bo con ging ht nhau. iu ny i hi s tng hp nhiu phn t sinh hc cn thit
xy dng cc t bo con. Gn nh tt c cc vi khun c mt nhim sc th trn n. Qu trnh
nhn i nhim sc th (replication) l mt phn khng th thiu trong phn chia t bo. Tnh trng
sao chp xy ra khi cc enzym ca vi khun s dng cc nhim sc th c nh mt khun mu
tng hp nhim sc th th hai ging ht n. Mun thc hin iu ny phi c sn ngun cung
cp deoxynucleotid kt hp vi phn t DNA mi sinh ra. Qu trnh ny phc tp hn ngi ta
ngh v cc enzym khc cng phi iu chnh s thch ng vi DNA cho php ti to ti u
nhim sc th. Cc qu trnh phc tp ny a ra mt vi c hi cho cc tc nhn khng sinh c
th tc ng ln c ch vi khun pht trin.
TNG HP DEOXYNUCLEOTID
Hnh 3-1. Tng hp tetrahydrofolate vi khun .

Ngun cung cp di do cc phn t giu nng lng nh: deoxyadenosin triphos-phat (dATP),
deoxyguanosin triphosphat (dGTP), deoxycytidin triphosphat (dCTP) v deoxythymidin
triphosphat (dTTP) l iu cn thit sn xut cc phn t DNA trong qu trnh nhn i DNA.
Vi khun s dng mt s ng tng hp sn xut cc khi vt liu ti to DNA.
Tetrahydrofolat (THF) mt ng yu t cn thit cho mt s con ng v c tng hp nh
sau (Hnh 3-1.): Enzym dihydro-pteroat synthase s dng dihydropterin pyrophosphat v para-
aminobenzoat (PABA) to thnh dihydropteroat, sau c chuyn i thnh dihydrofolat.
Dihydrofolat reductase sau chuyn i dihydrofolat thnh THF. THF cn thit cho s tng hp
cui cng ca mt vi nucleotid. Mc d con ngi d dng hp th folat - mt tin cht ca THF
t ch n, tuy nhin hu ht cc chng vi khun khng th lm nh vy v phi tng hp ng
yu t ny. Cho nn con ng tng hp ny l mt mc tiu hp dn cho cc hp cht khng

khun.
CC ENZYM TNG HP DNA
Enzym DNA polymerase chu trch nhim cho qu trnh nhn i nhim sc th ca vi khun,
nhng qu trnh ny cng cn cc enzym khc tham gia. Mt v d l cc topoisomerase kim sot
cc qu trnh siu xon hoc vn xon ca phn t DNA. hiu qu trnh siu xon phi nh
gi c nhng h qu vic to ra nhim sc th DNA xon c. Cc cu trc xon kp ca DNA
ch ra mt trng dn xon, cha 10 cp nucleotide trn mi lt xon c. Tuy nhin, bng cch vn
xon mt u ca DNA trong khi gi u kia c nh, c th tng hoc gim s lng cc cp
nucleotit mi lt xon c, vi 11 hoc 9 cp (Hnh. 3-2). iu ny dn n ko cng i vi cc
phn t DNA, c iu chnh do hnh thnh cc qu trnh siu xon. Khi gia tng s lng cc
cp nucleotit vi mi lt xon c, cc qu trnh siu xon c cho l thun. Khi gim cc qu
trnh siu xon b cho l nghch. Mt qu trnh tng t xy ra trong vi khun. Bi v cc b phn
ca nhim sc th c c nh do lin quan ti cc phc hp protein ln, cc qu trnh vn
xon xy ra trong mt phn khng th d tiu tan m to thm v dng siu xon. V vy cc qu
trnh vn xon t u? RNA polymerase l mt phn t ln khng th quay t do trong khi di
chuyn dc theo nhim sc th vi khun trong qu trnh phin m. V vy, khi RNA polymerase
vt ln theo cch ca n dc theo nhim sc th, tch si DNA nh n xy ra, cc qu trnh siu
xon thun xy ra pha trc enzym, trong khi cc qu trnh siu xon nghch tch t pha sau n.
V l thuyt, qu trnh siu xon qu mc c th gy kh khn cho s ti to DNA v phin m.
Hnh 3-2. Qu trnh siu xon trong cu trc xon kp ca DNA.

A. Vn xon si DNA dn n hnh thnh cc si xon kp. B. Trong qu trnh phin m, chuyn
ng ca RNA polymerase dc theo nhim sc th dn ti tch ly cc siu xon thuntrc cc
enzym v cc siu xon nghch ng sau n. (Trch dn c php ca Alberts B, Johnson A,
Lewis J, et al Sinh hc phn t ca t bo New York, NY: Garland Khoa hc; 2002:... 314) 9
hnh dung siu xon (bi si xon b ri) hy lm nh sau, tay tri gi cht giy xon mt tai
nghe in thoi bn ti im cch ng nghe khong 30 cm, tay phi cm si giy xon ti im
v vut cng si giy xon v pha ng nghe. Trong v d ny dy xon tai nghe ging nh si
xon nhim sc th DNA, tay phi l RNA polymerase di chuyn dc theo si nhim sc th. Lu
cch cc bi siu xon to thm trong dy xon v pha trc bn tay. By gi, hy th ng
nghe trong khng kh. Trng lc ng nghe ko dn lm mt cc bi siu xon khi si giy xon
tai nghe, ko si dy xon nh hnh vn xon. Nhng ng nghe by gi khng cn c nh, v
vy c th quay t do lm gim cng si giy xon.
Hnh 3-3. Ti to cc nhim sc th ca vi khun. Mt h qu chu k t nhin cc nhim sc th

ca vi khun l cc nhim sc th c ti to l lin kt vi nhau, i hi topoisomerase phn
chia thch hp.
Mt h qu chu k t nhin cc nhim sc th ca vi khun l sau khi hon thnh ti to, hai
nhim sc th t bo con sinh sn c s thng xuyn lin kt vi nhau (Hnh. 3-3). iu ny
hin din r rng mt tr ngi vi cc vi khun phn chia trong khi vi khun c gng phn bit
mt nhim sc th cho mi t bo con sinh sn c.
Cc vi khun vt qua c nhng vn ny nh to ra cc topoisomerases, cc enzym loi b
hoc thm cc bi si xon b ri vo DNA. Chng thc hin iu ny nh gn vo DNA, ct mt
hoc c hai si DNA, qua c mt di n ca DNA hoc to ra hai si DNA qua ch b ct v sau
loi b DNA. Vic thng qua mt hoc hai si DNA qua ch b ct thc cht loi b hoc thm
mt hoc hai bi si xon b ri vo nhim sc th. Nhim sc th cng c th b lin kt hai
nhim sc th lin kt vi nhau tip theo qu trnh ti to bn sao. Bng cch ny, vi khun c th
iu chnh mc siu xon trong nhim sc th ca h v cho php tch nhim sc th sau sao
chp DNA.
CU HI
1. Tetrahydrofolate cn cho mt s con ng lin quan n qu trnh tng hp ----------------------
--.
2. Cc nhim sc th ca hu ht cc vi khun l ------------------------.
3. ------------------------ l cc enzym iu ha qu trnh bi si xon DNA b ri.
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Chng 4: Xc nh nhy cm ca vi khun vi khng sinh
Dch|: DS. Nguyn Quang Vit, Cu sinh vin dc H Dc HN
Hiu nh: DS. V Th H
Chng ta tho lun v ba qu trnh vi khun u rt cn thit cho s sng cn ca chng v
khc bit tng ng ca chng vi cc qu trnh t bo con ngi: hnh thnh vch t bo, sn
xut protein ca vi khun v s nhn ln ca nhim sc th ca vi khun. Mi qu trnh ny cung
cp cc mc tiu khc nhau thuc khng sinh c ch vi khun. Khng sinh c chia thnh hai
nhm: Khng sinh dit c vi khun c gi l khng sinh dit khun (bactericidal) v nhng
khng sinh ch n thun ngn chn tng trng ca vi khun c gi l cc khng sinh km
khun (bacteriostatic). Cc khng sinh km khun da vo h thng min dch loi b cc vi
khun bng cch khng cho vi khun nhn ln trong c th ngi bnh.
Nng c ch ti thiu (Minimum Inhibitory Concentration-MIC) v nng dit khun ti
thiu (Minimum Bactericidal Concentration-MBC) l i lng nh lng tnh nhy cm ca mt
vi khun phn lp i vi mt khng sinh nht nh. Nh tn gi th hin, MIC l nng ti
thiu ca mt thuc khng sinh vn c th ngn chn s pht trin ca chng vi khun phn lp.
Tng t nh vy, MBC l nng ti thiu ca mt thuc khng sinh dn ti git cht vi khun
phn lp.
Trong thc t mt s th nghim c trin khai xc nh mt chng vi khun nht nh c
nhy cm hoc khng vi mt khng sinh c th khng. Theo Phng php Kirby-Bauer (k
thut khoanh giy khng sinh khuch tn trn thch), khoang giy tm khng sinh c b vo
a thch lng mt loi vi khun. Khng sinh khuch tn t cc khoang giy, qu trnh xc lp
mt gradient c nng thp dn nu cng xa khoang giy tm khng sinh. S tng trng ca vi
khun s b c ch trn din tch xung quanh cc khoang giy tm khng sinh. o ng knh trn
c th s dng xc nh c xem cc chng vi khun nhy cm hay khng vi mt thuc
khng sinh. Phng php Etests (Epsilometer test Epsilon) hot ng trn nguyn tc tng t,
ngoi tr s dng cc di di thay cho cc khoang giy tm khng sinh. Cc di c ngm tm
mt gradient gim dn nng khng sinh dc theo chiu di. Khi th cc di di vo a thch
lng mt loi vi khun, vi khun s pht trin cho ti cui ca di di ni nng khng sinh thp
nhng khng pht trin u ca di di c nng khng sinh cao. Vt c mng vi khun u
tin chm vo di di c s dng tnh MIC, c thang nh s nng ngay trn di h tr
xc nh MIC. Phng php canh pha long Broth vn hnh theo nguyn tc tng t, ngoi tr
khng sinh c pha long tt hn trong cc mi trng cht lng hn trong mi trng thch.
Trong cc th nghim ny, mi trng vi pha long ln nht ca khng sinh m vi khun
khng pht trin th chnh l MIC. Hin ti cc phng xt nghim vi sinh hu ht cc bnh
vin ln u s dng cc my da trn nhng nguyn tc ny t ng kim tra hng trm chng
vi khun phn lp.
LI KHUYN QUAN TRNG
H thng min dch dng nh tng i khng c hiu qu trong vic loi tr vi khun mt s
loi bnh nhim khun nh vim mng no v vim mng trong tim. Trong cc bnh nhim khun
ny, nn s dng khng sinh dit khun (bactericidal) thay v khng sinh km khun
(bacteriostatic).
CU HI
1. Khng sinh ------------------------ dit vi khun thay v c ch tng trng ca vi khun.
2. Phng php o lng s nhy cm khng sinh s dng khoang giy tm khng sinh b vo a
thch lng mt loi vi khun gi l phng php ------------------------
3. Cc phng phpo lng s nhy cm khng sinh bng cch pha long khng sinh trong mi
trng lng c gi l phng php ------------------------.
13
PHN II: CC TC NHN KHNG KHUN
Chng 5: Khng sinh tc dng ln thnh ca t bo

Dch: Nguyn Th T Oanh Sinh vin dc HN
Hiu nh: DS. V Th H
Nu thnh t bo (cell envelop) l o gip ca vi khun, th cc khng sinh nhm beta-

lactam, nhm glycopeptide, daptomycin v colistin l nhng ci n c kh nng lm thng
n. Nhng cht khng sinh ny tn cng thng t bo c chc nng bo v, bin chng tr
nn bt li i vi vi khun. Trong nhng phn tip theo, chng ti s ni v cch thc tiu
dit vi khun ca nhng khng sinh ny, nhng loi vi khun m chng c tc dng chng
li v c tnh ca nhng thuc .
Cc khng sinh -Lactam

Cu chuyn th v ca cc khng sinh nhm beta-lactam ny bt u vo nm 1928, khi
Alexander Fleming nhn thy rng mt trong nhng mu nui cy ca ng b nhim nm
mc ngn chn s pht trin ca vi khun. Bi v vt mc l mt loi Penicillium,
Fleming t tn nhng cht khng khun sinh ra bi loi mc ny l penicillin, cht u
tin ca mt dy di cc hot cht beta- lactam. S m t c im cht ny pht trin
nhanh chng v vo 194, nhng th nghim lm sng c tin hnh trn bnh nhn vi
nhng thnh cng ni bt.
Cu trc ct li cn thit ca penicillin l 1 vng gm 4 nguyn t gi l vng beta- lactam
(Hnh. 5-1). Nhng s ci tin ca cu trc c s ny dn n s pht trin ca mt vi hp
cht khng khun c hiu qu vi c im ph hot ng v cc tnh cht dc ng hc
ring ca mi cht. Nhng cht ny bao gm: nhm penicillin, nhm cephalosporin, nhm
carbapenem v nhm monobactam (Bng 5-1).Tuy nhin c iu quan trng cn nh rng
hot tnh khng khun ca mi hp cht beta-lactam c da trn nhng c ch c bn
ging nhau (Hnh. 5-2). Mc d hi qu n gin ha nhng c th ni rng, cc khng sinh
beta-lactam c th c xem nh l nhng cht c ch cc protein lin kt vi penicillin
(penicillin-binding proteins - PBPs) vn l nhng cht tng t lp peptidoglycan bao
quanh hu ht vi khun. tng c gi thuyt rng vng beta-lactam c cu trc bt chc
phn d-alanyld-alanine ca chui peptide m chng thng xuyn lin kt bi PBPs. PBPs
do lin kt vi vng lactam v khng tham gia vo vic tng hp peptidoglycan mi
(Hnh. 5-3). S ph v ca lp peptidoglycan dn n s ly gii ca vi khun.
Hnh 5-1. Cu trc vng beta-lactam

Bng 5-1: Khng sinh nhm beta-lactam

Nhm penicillin
Nhm cephalosporin
Nhm carbapenem
Nhm monobactam
Nh l trng hp vi tt c cc khng sinh, s khng ca vi khun vi nhm beta-

lactams c th c chia thnh 2 loi chnh: khng thuc t nhin v khng thuc thu c
(mc phi). Khng thuc t nhin (intrinsic resistance) lin quan n mt c ch khng
thuc m thuc bn cht cu trc hoc sinh l ca cc loi vi khun. V d cc knh porin
pha ngoi mng t bo ca tt c cc chng Pseudomonas aeruginosa khng cho ampicillin
i qua vo t bo cht v v vy tt c cc chng P.aeruginosa khng vi khng sinh
ny. Ngc li, khng mc phi (acquired resistance) xy ra khi mt vi khun tng
nhy cm vi khng sinh trc thu c mt t bin hoc nguyn liu di truyn khc l
m cho php n by gi chng li tc dng ca khng sinh . V d hu ht cc chng ca
P. aeruginosa nhy cm vi carbapenem l imipenem, thuc c kh nng gn vi cc PBP
ca cc vi khun ny bng cch vt qua knh protein c hiu c tm thy pha ngoi
mng t bo. Tuy nhin, sau phi nhim vi imipenem, cc t bin t pht c th xy ra
m kt qu l lm mt s sn xut ca cc knh protein ny. iu ny gy nn khng thuc
mc phi vi imipenem. Thc t m ni, khng thuc t nhin thng th hin rng tt c
cc chng ca cng mt loi vi khun khng vi mt khng sinh nht nh, trong khi
khng thuc mc phi nh hng ch mt vi chng ca mt loi vi khun.
Khng thuc thng do mt khng sinh b tht bi vi t nht mt trong vic ng u vi

6 cm by trong qu trnh m khng sinh nhm beta-lactam ng u vi vi khun gy
bnh (Hnh. 5-4) Sau cm by (su P) ny gm: (1) Penetration - S xm nhp: cc beta
lactam xm nhp km vo gian ni bo ca cc t bo c th ngi, vy nn vi khun m c
tr gian ny khng b phi nhim vi thuc. Mt khng sinh beta-lactam khng th git
mt vi khun nu n khng th tip xc c vi khun. (2) Porins knh porin: nu mt
khng sinh beta-lactam tip xc c vi khun, n phi tip cn c cc ch tc dng ca
n, trong trng hp ny l cc PBP (PBPs). vi khun gram dng, iu ny khng kh
bi v PBPs v lp peptidoglycan tng i d b tip cn, nhng trong vi khun gram m,
chng c bao quanh bi cc mng bo v bn ngoi (outer membrance). Cc beta-lactam
phi qua xuyn qua mng ny bng cch khuych tn qua cc knh porin, l nhng knh
protein nm mng ngoi.
15
Hnh 5-2: C ch hot ng ca cc khng sinh. A- Bnh thng, mt n v siu phn t
mi ca dissacaride l acid N-acetylmuramic acid (NAMA) v N-acetyl glucosamine
(NAGA) vo mt chui peptide c ni vi mt polymer peptidoglycan ang tn ti. iu
ny c th xy ra bi c ch gn ng ha tr ca mt cu glycerin (G) t mt chui peptide
ti chui khc thng qua hot ng xa tc ca mt PBP. B - Vi s hin din ca mt
khng sinh beta-lactam, qu trnh ny b ph v. Khng sinh beta-lactam lin kt vi PBP
v ngn n lin kt cu glycerin vi chui peptide
Hnh 5-3. C ch ca s c ch protein ni penicillin (PBP) bi cc khng sinh beta-lactam.

A- PBPs nhn ra v xc tc lin kt peptide gia 2 n v (subunits) alanine ca chui
peptide peptidoglycan. B- vng beta-lactam bt chc lin kt peptide ny. Do , PBPs c
gng xc tc vng lactam, do gy nn bt hot PBPs.
Nhiu vi khun gram m c cc knh porin m n khng cho php mt s beta-lactam nht
nh i qua ti t bo cht. (3) Pump-Bm: mt s vi khun sn xut cc bm y
thuc ngc ra ngoi (efflux pump), l nhng phc hp protein c kh nng vn chuyn
cc khng sinh va mi tin vo t bo cht quay ngc tr li ra bn ngoi. Nhng bm
ny ngn cn cc khng sinh tch ly trong t bo cht ti nng cho hot ng khng
khun. (4) Penicilinase (thc ra l cc beta-lactamase, nhng do khng bt u vi P nn
dng t penicilinase cho d nh): nhiu vi khun, k c gram m v gram dng, sinh ra cc
beta-lactamase, l cc enzyme phn hy cc beta-lactam trc khi chng gn vi cc PBP.
(5) PBPs: mt s vi khun sn xut cc PBP m n khng lin kt vi cc hot cht beta-
lactam vi i lc cao. nhng vi khun ny, cc beta-lactam n c ch tc dng ca
chng l cc PBP, nhng khng th bt hot c chng. (6) Peptidoglycan khng c mt:
c mt s t vi khun khng to peptidoglycan v do vy chng khng b nh hng bi cc
beta-lactam. c hiu qu, cc cht beta-lactam phi ng u thnh cng cc cm by
tim tng ny xung quanh. Mt lu l quan trng l cc khng sinh beta lactam l nhm
cc hp cht khng ging nhau. Mt vi thuc c th b chn ngay ti mt s bc nht nh
trong khi mt s khc c th vt qua khng cht kh khan.
Mt iu lu v cc enzym beta-lactamase l: Chng rt a dngiu ngha l mt s
enzym c tnh c hiu vi mt t khng sinh beta-lactam trong khi nhng enzym khc
chng li gn nh tt c cc khng sinh beta lactam
Hnh 5-4. Hot ng ca cc lactam c th b chn bi su c ch: (1) S xm nhp, (2)

cc porin, (3) cc bm tng thuc, (4) penicilinases (beta-lactamases), (5)penicillin binding
protein(PBPs) v (6) peptidoglycan.
17
Lch s:
Tnh c, Alexander Fleming tri qua k ngh 2 tun ngay sau khi ng nui cy trong
mi trng thch a b tp nhim sm. Bi v ng bit s khng th kim tra cc a
thch trong 2 tun v ng bn i ngh, ng chng nhit phng thay v 37 C lm
chm tc tng trng ca vi khun. K ngh ca ng thay i lch s nhn loi loi
ngi. Mc Penicillium pht trin nhit phng nhng khng th pht trin 37C. Nu
c Fleming khng c k ngh ny, ng y s khng bao gi quan st c cc tc dng dit
khun ca loi nm mc ny. V vy, cc k ngh thc s lm cho cng vic hiu qu hn
V d, cc beta-lactamase tit bi t cu vng tng i c hiu vi mt s loi penicilin,

trong khi cc beta-lactamse ph rng c tit bi mt s chng Escherichia coli and
Klebsiella spp. (spp. L t vit tt ca nhiu loi thuc mt chng vi khun) ph hy gn
nh tt c cc penicillin, cc cephalosporin v cc monobactam. Cc chng hoc cc loi vi
khun khc nhau sn xut ra cc loi beta-lactamase khc nhau a n cc kiu khng
khng sinh c bit. Do , s suy rng ra v cc beta-lactamase v tc ng ca chng ln
cc khng sinh c th phi c thc hin thn trng.
Mc d cn nhiu hn ch, cc khng sinh beta-lactam vn l mt trong nhng khng sinh
ph rng v hiu lc mnh nht cn li hin nay. Chng chim mt t l ln trong tng cc
khng sinh c k n mi nm.
Cc cu hi:
1. Cc khng sinh beta-lactam hot ng bng cch ngn cn hnh thnh cu trc ca
lp ca vi khun
2. Bnnhm chnh ca cc khng sinh beta-lactam l.
3. Cc khng sinh beta-lactam hot ng bng cch lin kt vi.
4.l nhng enzyme c kh nng phn hy cc khng sinh beta-lactam, do
lm bt hot tc dng ca khng sinh.
Cc penicillin
Mi mt penicillin bao gm mt vng thiazolidine gn vi mt vng beta-latam m bn thn

cc penicillin c thay i bi mt mch nhnh khc nhau (R Hnh. 5-5). Trong khi
vng thiazolidine beta lactam cn thit cho hot ng khng khun, mch nhnh thay i
to ra nhiu dn xut penicillin khc nhau vi cc tnh cht dc l v ph hot ng
khng khun khc nhau.
Kt qu ca s thay i mch nhnh R, nhm penicilin chia thnh mt vi di nhm: cc

penicillin t nhin, cc penicillin khng t cu, cc aminopenicillin v cc penicillin ph
rng (Bng 5-2). Ngoi ra, mt s penicillin c dng phi hp vi cc cht c ch beta-
lactamase, gip m rng ng k s lng loi vi khun nhy cm vi nhng khng sinh
ny. Cc thuc trong mi di nhm c nhng tnh cht dc ng v ph tc dng ging
nhau nhng c th kh khc nhau so vi cc cht ca di nhm khc.
Hnh 5-5. Cu trc ca cc penicillin.
Bng 5-2. Nhm penicillin

Loi Thuc ng tim Thuc ng ung
Cc penicillin t nhin Penicillin G Penicillin V
Cc penicillin khng t cu Nafcillin, oxacillin Dicloxacillin
Cc aminopenicillin Ampicillin Amoxicillin, ampicillin
Cc aminopenicillin + cc Ampicillin-sulbactam Amoxicillin-clavulanate
cht c ch beta-lactamase
Cc penicillin ph rng Piperacillin, ticarcillin
Cc penicillin ph rng + cc Piperacillin -tazobactam,
cht c ch beta-lactamse Ticarcillin-clavulanate
Cc Penicilin t nhin
Cc Penicilin t nhin gm penicillin G v penicillin V, l nhng cht u tin ca gia nh
khng sinh penicillin nhng vn c nhiu iu ni v iu tr nhim khun. Chng c
gi l penicillin t nhin v chng c th c chit xut trc tip t nui cy Nm
Penicillium. Mch nhnh R ca penicillin G c th hin trong Bng 5-6 v cha 1 vng
hydrophobic benzene.
19
Hnh 5-6. Chui R ca penicillin G
Bi v gn nh tt c vi khun c thnh t bo u cha thnh phn peptidoglycan, khng c

g ngc nhin rng penicillin t nhin c ph tc dng ln mt vi loi vi khun gram m,
gram dng v k kh cng nh mt s xon khun. Mc d ph hot ng rng, hu ht vi
khun hoc khng thuc t nhin hoc by gi khng thuc mc phi vi cc penicillin t
nhin. Hiu c nhng nguyn nhn khng ny c th gip ghi nh cc loi vn cn
nhy cm. Ni cch khc, ph vi khun ca penicillin t nhin c th c s dng nh l
mt c s cho vic nh ph ca cc loi penicillin khc. Su c ch khng (su P) gii
thch s khng thuc vi cc penicillin t nhin: (1) s xm nhp cc penicillin t nhin,
nh hu ht cc beta-lactam, thm nhp km vo trong ngn ni bo ca t bo ngi, vy
nn nhng vi khun c tr trong cc ngn ny nh l Rickettsia v Legionella c bo v
khi tc dng ca khng sinh. (2) knh Porin mt s vi khun gram m nh l E.coli,
Proteus mirabilis, Salmonella enterica v Shigella spp. c cc porin mng ngoi khng
cho php s vt qua ca penicillin t nhin khng thn nc ti t bo cht. (3) Bm
mt s vi khun gram m, nh l P. aeruginosa c bm tng thuc ngn cn s tch ly ca
penicillin trong t bo cht. Mc d bn thng bm ny c th to ra mt s thay i nh
v tnh nhy cm, chng c th hot ng cng vi men penicilinase v cc knh porin c
tc ng to ln hn. (4) Penicilinase nhiu vi khun k c gram dng (staphylococci) v
gram m (mt s chng Neisseria v cc Haemophilus, nhiu loi vi khun rut khng lit
k mc (2) v mt s vi khun k kh nh l Bacteroides fragilis), to ra penicilinase phn
hy cc penicillin t nhin. (5) PBPs mt s vi khun sn xut PBPs khng lin kt vi
cc penicillin t nhin vi i lc cao (v d mt s chng Streptococcus pneumonia). (6)
Peptidoglycan mt s vi khun nh l Mycoplasma v Chlamydia spp., khng to
peptidoglycan v do khng b nh hng bi cc penicillin t nhin.
Mc d nhng hn ch ny, cc penicillin t nhin vn c s dng iu tr nhim trng

gy ra bi mt s vi khun gram dng, c bit streptococci, mt s vi khun k kh v mt
s spirochetes (Bng 5-3). Mc d mt s t vi khun gram m nh l Neisseria meningitides
v mt s chng ca Haemophilus influenza khng sinh cc beta-lactamse. Do vn cn
nhy cm vi penicillin.
PENICILLIN KHNG T CU
Cc penicillin khng t cu ( cn c gi l penicillin khng penicillinase) c phn cng
knh trn mch nhnh R ca chng ngn cn cc beta-lactamse do t cu sinh ra gn vi
khng sinh (Hnh. 5-7). Kt qu l nhng penicillin ny hiu qu trong iu tr nhim trng
gy ra bi t cu vng S. aureus v t cu da Staphylococcus.Tuy nhin chng khng c kh
nng lin kt vi cc PBP ca 2 nhm t cu c bit khng methicillin gi l t cu vng
khng methicillin (methicillin khng S.aureus - MRSA) v t cu da khng methicillin
(methicillin khng S.epidermidis - MRSE).
Hnh 5-7. Chui R ca nafcillin
Bi v chng khng th lin kt vi PBPs ca vi khun MRSA v MRSE, cc penicillin

khng t cu khng c tc dng tr cc chng vi khun ny (lu methicillin l thuc nhm
penicillin khng t cu khng cn c mt trn th trng nhng n l i din ca phn
nhm penicillin khng t cu v ph hot ng ca nhm ny). Penicillin khng t cu km
hiu qu hn penicilin t nhin v tc dng ln streptococci v khng thng xuyn c s
dng iu tr. Khng c mt cht no trong nhm penicillin ny hot ng chng li
21
enterococci. Cn na, s cng knh ca mch nhnh lm cho kh nng thm nhp ca
nhnng khng sinh ny vo hu ht cc vi khun khc l hn ch v ni chung chng ch
c s dng iu tr nhim khun do t cu (Bng 5-4). Nhm ny bao gm cc khng
sinh: nafcillin, oxacillin v dicloxacillin.
Nhm Aminopenicillin
Cc aminopenicillin gm ampicillin v amoxicillin c ph hot ng tng t penicillin t
nhin ngoi tr mt iu: Mt nhm amino c thm vo trong chui mch nhnh lm tng
tnh phn cc ca chng v cho php chng i qua cc porin mng ngoi ca mt s trc
khun rut gram m nh E.coli, P. mirabilis, S. enterica v Shigella spp.(Hnh. 5-8). iu
ny gip m rng ph tc dng ca cc aminopenicillin bao ph c cc vi khun ny.Tuy
nhin, cc amiopenicillin c chung c im ca cc penicillin t nhin l d b tn cng bi
cc beta-lactamse, v nhiu vi khun gram m m ban u nhy cm vi cc aminopenicillin
by gi li khng do vi khun thu c cc gen m ha beta-lactamse.
Hnh 5-8. Chui R ca ampicillin
PHI HP AMIOPENICILLIN/CC CHT C CH BETA-LACTAMASE:

Nhiu cht c nghin cu pht trin c ch cc -lactamse tit bi nhiu vi khun
gam dng v m. Nhng cht c ch ny c cu trc tng t penicillin v do lin kt
vi cc -lactamse, lm cho n mt hot tnh. Hai trong nhng cht c ch ny l:
clavulanate v sulbactam, c s dng cng vi cc aminopenicillin m rng ph hot
ng. Ampicillin- sulbactam l cng thc ng tim v amoxicillin-clavulanate l cng
thc ng ung ca dng phi hp ny. Sulbactam v clavulanate bt hot -lactamse tit
bi nhiu vi khun Gram m, Gram dng v k kh. Kt qu l chng m rng ph khng
khun ca aminopenicillin mt cch ng k (Bng 5-6)
Hnh 5-9. Chui R peperacillin
Penicillin ph rng
Cc penicillin ph rng bao gm piperacillin v ticarcillin. Cc mch nhnh ca nhng
cht ny cho php cc thuc ny xm nhp vo vi khun gram m mnh hn so vi cc
aminopenicillin. V d, mch nhnh ca piperacillin l phn cc, n lm tng kh nng vt
qua knh porin mng ngoi ca mt s vi khun gram m (Hnh. 5-9). (Nhn tin,
piperacillin c t tn t tn mch nhnh ca n cha dn xut piperazin). Ngoi ra, ni
chung cc penicilin ph m rng bn hn vi s phn hy bi cc lactamse tit bi gram
m so vi cc aminopenicillin, mc d chng vn b phn hy vi mt vi trong s nhng
enzym ny. Do , so snh vi cc aminopenicillin, cc penicillin ph m rng tc dng ln
trc khun gram m bao gm nhiu chng P. aeruginosa. Chng gi nguyn hot tnh ph
trn mt vi gram dng tng t cc penicilin t nhin, nhng ging nh cc penicillin t
nhin, nhm ny b phn hy bi cc -lactamase do t cu tit. Chng c ph hot ng
kh hp tc dng ln vi khun k kh (Bng 5-7). Piperacillin c ph hot ng rng hn l
ticarcillin.
23
Phi hp penicillin ph rng/cht c ch beta- lactamase
Tim lc khng khun y nht ca cc penicillin t c bng cch phi hp cc
pencillin ph rng vi cc cht c ch lactamase. C 2 s phi hp c hiu lc l
piperacillin-tazobactam v ticarcillin-clavulanate. Cht c ch -lactamase lm mt tc
dng nhiu loi beta-lactamase lm cho cc enzym ny khng th phn hy cc penicilin ph
m rng. Do , phi hp ny gip m rng ph tc dng ca chng. Do , piperacillin-
tazobactam v ticarcillin-clavulanate to cc penicillin c ph rng ton din, vi ph hot
ng khng li hu ht vi khun hiu kh gram dng: bao gm nhiu chng t cu sn xut
beta- lactamamse, hu ht vi khun hiu kh gram m v gn nh l tt c vi khun k kh
ngoi tr Clostridium difficile (Bng 5-8). Theo nh d on da trn ph hot ng ca
thnh phn penicillin, piperacillin-tazobactam c ph rng hn ticarcillin-clavulanate. Ph
hot ng ni tri khng li vi khun gram m, gram dng v k kh ca n khin

piperacillin- tazobactam l mt trong nhng khng sinh cn hiu lc mnh nht hin nay
LU : Penicillin G v penicillin V: Loi no tim? Loi no ung?

Nhng ch ci trong tn penicillin G v penicillin V c th c dng ghi nh nhng
khng sinh ny thng c dng nh th no. Mc d khng tht s chnh xc, gi d rng
ch G trong penicillin G ngha l thuc ny b ph hy trong d dy (Gastric) v ch
V trong penicillin V ngha l thuc ny b ph hy trong tnh mch (vein). Do ,
penicillin G c dng ng tim v penicillin V c dng ng ung.
c tnh
Nhng tc dng khng mong mun ca cc penicillin l tng i ging nhau. c tnh 3 %
n 10 % ngi d ng vi nhng cht ny. Nh hu ht khng sinh, penicillin c th gy
bun nn, nn, tiu chy. Chng cng c lin quan gy st, pht ban, bnh huyt thanh,vim
thn k, c gan, c h thn kinh, bin dnh hng cu do thuc. Ni my ay, ph mch ,
v sc phn v c th xy ra v c coi nh l phn ng qu mn tc th.Trong tt c
nhng phn ng ny, ci ng s nht l sc phn v, n him nhng li e da tnh mng.
Bnh nhn d ng mt penicillin nn lu bnh nhn c th b d ng vi tt c penicillin, v
d ng cho c th m rng sang cc khng sinh - lactam khc.
Cc penicillin khc nhau nhiu v ph hot ng ca chng, c bit tc dng ln vi khun
gram m. Ph hot ng ca nhng cht ny tc dng ln vi khun gram m c th c tm
tt li nh sau: (1) cc penicillin khng t cu khng tc dng ln vi khun gram m, (2)
penicillin t nhin tc dng ln N.meningtidis v mt s chng ca H. influenza, nhng ch
mt s t vi khun gram m khc.(3) Ph tc dng ca cc aminopenicillin c m rng
bao gm nhng vi khun ny cng vi mt s trc khun ng rut gram m nh l
ccchng nht nh ca E.coli, P.mirablis, S.enterica v Shigella spp. khng sn xut -
lactamase.(4) cc penicillin ph m rng tc dng nhiu hn trn cc trc khun rut gram
m v quan trng l P.aeruginosa. ( 5)Cui cng, thm cht c ch beta- lactamase vi
penicilin ph m rng m rng danh sch ny ra gn hu ht cc trc khun rut gram m.
Cu hi:
5 . Tt c penicillin c cu trc c bn, bao gm 1 vng thiazolidine lin kt vi mt.
vi mt.thay i
6 . Cc penicillin hot ng bng cch lin kt vi., n l enzym ca vi khun c
chc nng ging vi
7. Cc penicillin t nhin c ph hot ng trung bnh tc dng ln vi khun hiu kh gram
dng v vi khun k kh nhng hot ng km trn vi khun ..hiu kh. v hu ht vi
khun khng in hnh.
8. Cc penicillin khng t cu c tc dng trong iu tr nhim trng gy ra bi.
9. So snh vi cc penicillin t nhin, c aminopenicillin ph hot tnh ci thin hn trn
..
10. Thm mt cht c ch beta- lactamase vi mt aminopenicillin lm m rng ph hot
ng tc dng ln.. hiu kh, bao gm.
25
11. Khi s dng kt hp cc cht c ch beta- lactamase vi cc penicillin ph m rng l
mt trong nhng liu trnh khng sinh mnh nht hin nay v tc dng ln hu ht
.hiu kh,.hiu kh v.
Cc Cephalosporin
Cc cephalosporin c tn nh vy l ly tn loi nm Cephalosporium acremonium, loi
l loi sn xut khng sinh u tin trong nhm ny. Thm ch hn c cc penicillin, nhng
cht ny to nn mt h m rng rt nhiu cc khng sinh trong nhm - lactam. Vi vai tr
, chng gn nh c phn loi nh hn thnh cc th h. Bi v cc cht trong mi th
h c mt cht tng t v ph hot ng, s sp xp theo h thng ny c ch trong vic
nh cc tnh cht ca cc cephalosporin.
Mi cephalosporin bao gm mt nhn vi 2 mch nhnh (Hnh. 5-10). Nhn l 7-

aminocephalosporanic acid, n tng t vi nhn ca cc penicillin ngoi tr rng vng
beta- lactam c ni vi mt vng dihydrothiazine su nguyn t thay v 1 vng
thiazolidine 5 nguyn t (so snh Hnh. 5-10 vi Hnh. 5-5). Vng nhn trung tm ca cc
cephalosporin c 2 iu thun li hn nhn penicillin: (1) V bn cht, n kh b chia ct
hn bi cc - lactamase v (2) n c 2 nhnh R1 v R2 u c th b thay i. iu ny
mt phn gii thch s lng ln cc cephalosporin c sn trn th trng hin nay.
Nh cc khng sinh - lactam khc, cc cephalosopin pht huy tc dng ca chng bng
cch lin kt v c ch cc PBP, do ngn cn s tng hp peptidoglycan thch hp.
Hnh 5-10. Cu trc cc cephalosporin

Mc d peptidoglycan l mt thnh phn cu to hu ht vi khun, nhng cc
cephalosporin khng tc dng ln vi chng v loi vi khun nht nh . Tng t cc
penicillin, su c ch khng thuc gii thch s khng vi cc cepahlosoprin: (1) s xm
nhp cc cephalosoprins, ging nh hu ht cc - lactam, xm nhp km vo gian ni
bo ca t bo ngi, vy nn vi khun m hu ht c tr trong khong gian bo ny nh l
Rickettsia v Legionella c bo v. (2) Porins mt s vi khun gram m nh l
P.aeruginosa, c cc porin mng ngoi khng ch php s i qua ca nhiu cephalosporin
vo trong t bo cht. (3) Bm mt s vi khun nh l P.aeruginosa, s dng bm tng
thuc y khng sinh ra khi t bo cht . (4) Cc Penicillinase (thc cht l cc -
lactamase ) nhiu vi khun gram m nh l Enterobacter v Citrobacter spp., to ra cc
beta- lactamases ph hy nhiu cephalosopin. (5) PBPs mt s vi khun, nh enterococci
v Listeria monocytogenes, sn xut PBPs khng lin kt vi hu ht cc cephalosporins vi
27
i lc cao.( 6) Peptidoglycan mt s vi khun nh l Mycoplasma v Chlamydia khng
to peptidoglycan v do khng b nh hng bi cc cephalosporins.
C mt vi iu tng qut ha v ph hot ng ca cc cephalosporin. u tin, vi ngoi
l l cc cht thuc th h th nm mi, mi th h ni tip nhau c ph rng dn chng li
vi khun hiu kh gram m. Th 2, cng vi mt vi ngoi l quan trng, cc cephalosporin
c hot tnh hn ch trn cc vi khun k kh. Ba l, hot ng ca nhng cht ny chng li
vi khun gram dng hiu kh l thay i khc nhau gia cc cht, vi ceftaroline th h
nm c hot ng mnh nht chng li nhng vi khun ny.
CC CEPHALOSPORIN TH H I:
Cc cephalosporin th h I c s dng rng ri bao gm cefadroxil v cefazolin (Bng 5-
9). Tt c cc cht trong nhm ny c chung ph hot ng chng li cc chng vi khun
khc nhau.
im mnh ca cc cephalosporin th h 1 l hot ng chng li cu khun (cocci) gram
dng hiu kh nh l t cu (staphylococci) v lin cu (streptococci) (Bng 5-10). Mch
nhnh R1 ca nhng cht ny bo v vng lactam khi s phn hy bi cc beta- lactamase
tit bi t cu (Hnh. 5-11).
Kt qu l chng c ch trong vic iu tr nhim trng gy ra bi nhiu chng ca

Staphylococcus aureus.
Cc cephalosporin th h I khng th lin kt vi cc PBP ca MRSA v MRSE hoc nhiu

chng Streptococcus pneumonia- khng penicillin- cao; nhng cht ny khng c hiu qu
chng li nhng vi khun ny. Nh cp trc, hu ht cc cephalosporins cng thiu
hot ng chng li L. monocytogenes v cu rut (enterococci).
Cc cephalosporin th h I c hot tnh hn ch chng li vi khun gram m hiu kh v ty

facultative, c bn l do mch nhnh ca nhng cht ny khng sc bo v khi cc
beta- lactamases ca hu ht vi khun gram m, mc d n c kh nng bo v vng beta-
lactam khi b ct i bi beta- lactamases tit bi t cu. Tuy nhin, mt vi chng ca
E.coli, Klebsiella pneumonia v P.mirabilis vn nhy cm.
Cc cephalosporin th h I c ph hot ng mc yu n trung bnh chng li vi khun
k kh, vi khun ni bo v spirochetes..
CC CEPHALOSPORIN TH H II:
Cc cephalosporin th h II c chia thnh 2 nhm: cc cephalosporin tht s (nh l
cefuroxime) v cc cephamycin (bao gm cefotetan v cefoxitin) (Bng 5-9). Cc
cephamycin l cc dn xut ca hp cht ban u c ngun gc c chit xut t vi khun
Streptomyces lactamdurans thay v loi nm C. acremonium.
Hnh 5-11. Cu trc ca cefazolin
29
Hnh 5-12. Cu trc cefotetan. c im ca nhm cephamycin l vng cha nhm methoxy
Chng c 1 nhm methoxy thay cho v tr ca hydrogen trn vng beta- lactam ca nhn
cephalosporin (Hnh. 5-12). Do , nhng cht ny khng thc s l cc cephalosporin
nhng c t trong nhm ny v chng tng t v mt ha hc v dc l.
Cc cephalosporin th h II ring bit khc nhau hot ng ca chng chng li vi khun

gram dng hiu kh (Bng 5-11). Ni chung, cc cephalosporin thc s hot ng chng
li cu khun gram dng hiu kh nh cc khng sinh cephalosporin th h I. Cc
cephamycin (cefotetan and cefoxitin) c ph hot ng tng i hn ch chng li nhm vi
khun ny. u im ca cc khng sinh th h II l hot ng chng li vi khun gram m
hiu kh v ty facultative c tng thm. Cc khng sinh th h II c hiu lc mnh
hn chng li E.coli, K.pneumoniae v P.mirabilis so vi cc khng sinh th h I v cng
hot ng chng li Neisseria spp. (cccephalosproins thc s cn tc dng trn H. influenza
(bao gm c cc chng sn xut beta- lactamases). Bi v vic thm vo nhm methoxy trn
vng beta- lactam (Hnh. 5-12), cc cephamycins cng tng thm s n nh vi cc beta-
lactamase ca mt vi vi khun hiu kh nh B. fragilis. Tuy nhin, li ch ny b tr gi,
l nhm methoxy khin cho hot ng ca cc cephamycin chng li staphylococci v
streptococci b thu hp bi v i lc vi cc PBP ca nhng vi khun ny gim.
CC CEPHALOSPORIN TH H 3:
Cc cephalosporin th h 3 c s dng rng ri bao gm: ceftriaxone, cefotaxim, v
ceftazidine (Bng 5-9) . Ni chung, cc cht trong nhm ny c ph chng li cc vi khun
hiu kh gram m trung bnh (Bng 5-12) v c ch hu ht cc chng ca S. pneumonia -
nhy vi- penicillin . Cc cephalosporin th h III cng hot ng chng li cc spirochete
l Borrelia burgdorferi nhng hot ng chng li vi khun k kh rt t.
S thay i ph bin ca cu trc nhiu cephalosporin th h III l dng nhm

aminothiazolyl ti R1 (Hnh. 5-13). C mt cu trc ny ti v tr R1 khin s xm nhp ca
nhng cht ny qua mng ngoi vi khun tng ln, i lc vi PBPs tng v s n nh tng
ln khi c mt cc beta- lactamse c m ha bi cc plasmid ca vi khun hiu kh v
gram m ty facultative. Do , nhng cht ny tng hot ng chng li E. coli,
Klebsiella spp., Proteus spp., Neisseria spp., v H. influenza so vi cc cephalosporin th h
II. Ngoi ra, nhiu chng Enterobacteriaceae, bao gm Enterobacter spp.,
Citrobacter freundii, Providencia spp., Morganella morganii, v Serratia spp.,ban u cng

th hin tnh nhy cm vi cc cephalosporin th h III.
Hnh 5-13. Cu trc cefotaxim. Nhm aminothiazolyl l kinh in ca nhiu khng sinh
cephalosporin th h III.
31
Tuy nhin nhng vi khun ny c th sn sinh AmpC -lactamases gy khng thuc trong
qu trnh iu tr. Do , hin ny nhim trng bi nhng vi sinh vt ny nn hoc l khng
nn iu tr vi cc cephalosporin th h III hoc l nn iu tr vi nhng khng sinh ny
cng vi mt khng sinh th 2 khc, k c nu chng vn nhy cm khi test in vitro.
Mt khuyt im ca hu ht cc cephalosporin l thiu hot ng chng li P. aeruginosa.

gii quyt vn ny, mch nhnh aminothiazoyl R1 ca ceftazidime c ci tin bng
cch thm mt nhm carboxypropyl, n lm tng hot ng chng trc khun m xanh.
Khng may, s ci tin ny cng dn n i lc vi PBP ca staphylococci gim. Kt qu l,
ceftazidime tng hot ng chng P.aeruginosa nhng hot ng chng S.aureus b gii
hn.
Gia nhng cephalosporin th h III, ceftriaxone l ng ch bi thi gian bn thi di

ca n. Cht ny c s dng rng ri bi v s thun tin v liu mt ln mt ngy ca n.
Cc cephalosporin th h IV
Nh nhc n trc , cc cephalosporins l nhng cht khng khun mnh nht nhng
chng d b phn hy bi AmpC beta-lactamase ca nhiu chng Enterobacteriaceae. Ngoi
ra, hot ng chng P. aeruginosa ch t c nh i li hot tnh khng t cu gim.
Nhng c gng gii quyt nhng thiu st ny dn ti s ci tin mch nhnh R2 ca cc
cephalosporin th h III trong khi gi nguyn nhm aminothiazolyl c kt qu cao ti v tr
R1. (Hnh. 5-14) Kt qu ca nhng c gng ny l to ra cephalosporin th h 4 cefepime.
Cc mch nhnh ca cefepim cho php xm nhp nhanh qua mng ngoi t bo ca vi khu
gram m bao gm P. aeruginosa. Chng cng lin kt vi cc PBP ca nhng vi khun ny
vi i lc cao nhng bn ch tng i vi s phn hy bi cc beta- lactamases do gram m
tit ra, bao gm cc AmpC beta- lactamases (mc d ngha trn lm sng cn tranh ci).
Nhng tnh cht ny t c khng phi mt i hot ng chng li cu khun gram dng
hiu kh. Do khng sinh mnh ng kinh ngc ny c cc im ni bt nht ca cc
cephalosporin th h III khc nhau (hot tnh chng trc khun m xanh khng km vic
mt i hot ng chng t cu) v c th cng nng cao hot ng chng li nhiu
Enterobacteriaceae. Cefepime c tc dng hn ch trn k kh. (Bng 5-13)
Hnh 5-14. Cu trc cefepime. Nhm cu trc in hnh ca cephalosporin th h III R1 l

aminothiazolyl trong khi R2 l nhm pyrrolidine phn cc
CC CEPHALOSPORIN TH H NM
Ceftaroline l mt cephalosporin mi m rng hot ng chng li cu khun gram dng
hiu kh, khin cc chuyn gia cho n nh l mt khng sinh th h nm. Vng 1,3- thiazole
c thm vo mch nhnh R2 ca cephalosporin ny, lm tng kh nng ca n lin kt vi
PBP ca t cu staphylococci khng methicillin (Hnh.5-15). Kt qu l ceftaroline c hot
ng chng cocci gram dng hiu kh vt tri bao gm Staphylococcus aureus-khng -
methicillin v Staphylococcus epidermidis-khng methicillin v cc chng Streptococcus
pneumonia-khng-penicillin (Bng 5-14). Cc hot ng ca n chng li vi khun gram m
hiu kh tng t hot ng ca cefotaxim v ceftriaxone, n thiu hot ng chng li trc
khun m xanh. Ceftaroline cng c hot ng chng li vi khun gram dng k kh nhng
cng khng chng li vi khun gram m k kh. Khng sinh ny c s dng di dng
ceftaroline fosamil tin thuc khng c hot tnh, cht ny nhanh chng chuyn thnh
ceftaroline c hot tnh.
Hnh 5-15. Cu trc ceftaroline. Vng 1,3-thiazole R2 lin quan n hot tnh chng li
cc chng Staphylococcus aureus khng-methicillin
33
c tnh :
Mt trong nhng im hp dn ca cc cephalosporin l lch s dng thuc tng i an
ton ca chng.Him khi nhng cht ny gy nn phn ng qu mn tc th bao gm pht
ban, my ay, sc phn v . Gn 5% n 10% c th d ng vi penicillin cng c phn ng
vi cephalosporin. Do , khuyn co thng xuyn a ra l vi tin s phn ng qu mn
tc thi nghim trng nh l ph mch v sc phn v vi penicillin khng c iu tr
vi cc cephalosporin. Cc tc dng khng mong mun him gp khc bao gm gim bch
cu trung tnh, ri lon mu, tan mu,tiu chy v tng cc xt nghim chc nng gan.
Cefotetan c th gy gim protrombin huyt v khi s dng vi ru th gy phn ng cai
ru ging nh dng disulfiram. Tt c nhng tc dng ny lin quan ti nhm
methylthiotetrazole moiety ti R2 ca cht ny (Hnh. 5-12). Bi v ceftriaxone c o
thi qua mt, liu cao ca khng sinh ny c th gy cn mt (bn mt).
Lch s
Cc cephalosporin c tm thy bi nh khoa hc ngi Giuseppe Brotzu vo nm 1940.
ng y rng mu nc bin c thi ra t nc thi ca Cagliari, , c lm sch
mt cch c nh k, c mt hin tng m ng y nghi ng l nc thi c lm sch l
do s sn xutnhng cht c kh nng c ch vi khun c sinh ra bi s pht trin ca vi
sinh vt khc trong nc. Cui cng ng y tm ra loi vi sinh vt Cephalosporium
acremonium v ch ra n thc s sn xut c mt cht c ch s pht trin ca vi
khun. Nhng cht ny tr thnh nhng cht c bn m cc cephalosporin u tin c
tng hp t chng.
Tm li, cc cephalosporin khc nhau ni bt cc hot ng ca chng, nhng theo cc th

h sau y: (1) Khng sinh th h I c ph chng li tt cc vi khun Gram dng hiu kh.
(2) cc khng sinh th h II c tc dng chng li trung bnh cc vi khun gram dng hiu
kh, vi khun gram m hiu kh v mt s vi khun k kh. (3) Cc khng sinh th h III c
ph chng li mnh cc vi khun gram m hiu kh. (4) Cc khng sinh th h IV c ph c
bit tng mnh hot tnh chng li cc vi khun gram m hiu kh. (5) cc khng sinh th h
V c ph chng li mnh cc vi khun gram m hiu kh v hot tnh tuyt vi chng li vi
khun gram dng hiu kh.
CU HI
13. Cc cephalosporin c chia nh thnh cc nhm v l mt nhm ln thuc nhm ln
hn gi l
14. Ging vi penicillin, cc cephalosporin hot ng bng cch lin kt vi - l enzyme
ca vi khun c chc nng tng hp peptidoglycan.
15. Cc cephalosporin th h I c tc dng trong iu tr nhim trng gy ra bi vi khun
hiu kh.
1 6. So snh vi cc khng sinh th h I, cc cephalosporin th h II tng ph hot ng

chng li cc vi khun hiu kh v mt s khng sinh ny cng c hot tnh chng li vi
khun
17. Cc khng sinh cephalosporin th h III c tc dng trong iu tr nhim trng gy ra bi
vi khun hiu kh.
18. So snh vi cc khng sinh th h III, khng sinh cephalosporin th h IV c ph hot
ng chng li cc vi khun gram m hiu kh rng hn, bao gm v cc thnh phn khc
ca
19. Khng ging nh cc cephalosporin khc, cc cephalosporin th h V c ph hot ng
chng li cc chng S.aureus.
20. S dng liu cao ca c lin quan ti gy cn mt.
21. Cc cephalosporin nn c s dng thn trng vi tng c nhn khi m c phn ng
qu mn tc thi nghim trng vi
35
Nhm carbapenem
Nu xem cc lactam nh l mt gia nh rng ln th cc carbapenem l nhng th h tr

nht rt nng ng i xe hi vi ng c mnh v mang nhng b o qun thi trang. Nhng
khng sinh ny l mt trong nhng khng sinh ph rng nht c s dng ngy nay. Vi
vai tr nh vy, chng thng xuyn nm trong ch nh u tin cui cng chng li cc
vi khun m khng cc khng sinh khc. Bn thuc thuc nhm ny bao gm imipenem,
meropenem, doripenem, v ertapenem c sn trn th trng hin nay (Bng 5-15).
Cu trc ca cc carbapenem lin quan ti cu trc cc penicillin hay cephalosporin (Hnh 5-

16). Vng lactam c ni vi mt vng gm nm nguyn t vi cc nhnh khc nhau.
Vng nm nguyn t khc vi vng thiazolidin ca cc penicillin 2 im (Hnh 5-16):
Nhm methylene thay th lu hunh S v vng c cha mt lin kt i.
Cu trc ca cc carbapenem to ra 3 tnh cht gip cho ph hot ng rng mt cch ni

bt ca chng. u tin, nhng phn t ny kh l nh v c cc c im cho php chng
s dng knh porin c bit mng ngoi t bo ca vi khun gram m gn vi cc PBP.
Hai l, cu trc ca carbapenem lm cho chng bn vng trc s ph hy ca cc
lactamase. Ba l, cc carbapenem c i lc vi nhiu loi PBP nhiu loi vi khun khc
nhau. Kt qu ca ba tnh cht ny l cc carbapenem rt d dng i vo c trong cht t
bo, bn vi s ph hy ca lactamase nm trong cht t bo v lin kt vi cc PBP
gy cht t bo vi khun.
Vic khng cc carbapenem xy ra khi vi khun nh bi c cc im mnh ca nhng

khng sinh ny. V d, trc khun m xanh c thin hng pht trin khng thuc bng cch
t bin thu c gy nn s mt kh nng sn xut cc knh porin mng ngoi c s
dng bi carbapenem i vo t bo cht. iu ny xy ra cng vi vic tng sn xut cc
bm tng thuc hn ch s tch ly ca thuc trong t bo cht. Cc chng Enterococcus
faecium v MRSA khng bi v chng sn xut cc PBP thay i m chng khng lin
kt c vi cc carbapenem. Cui cng, mt s vi khun c kh nng sn xut cc
lactamase cc k mnh c kh nng ph hy cc carbapenem.
Imipenem
Imipenem l khng sinh carbapenem u tin c mt trn th trng M. V mt cu trc,
cht ny khc cc carbapenem ch n thiu mch nhnh R1 (Hnh. 5-16).
Bng 5-15. Cc carbapenem
Thuc tim Thuc ung
Imipenem/cilastatin Khng c
Meropenem
Doripenem
Ertapenem
Hnh 5-16. Cu trc carbapenem. Cc vng th hin s khc nhau vi cu trc chnh ca
penicillin
Chng nhanh chng b phn hy thn bi enzyme gi l dehydropeptidase. Kt qu l n

c dng cng vi cilastatin, mt cht c ch enzyme ny.
Imipenem c ph hot ng chng li nhiu tc nhn vi khun gy bnh (Bng 5-16). Hu

ht cc lin cu, bao gm nhiu chng S. pneumonia - khng-penicillin, l nhy cm vi
khng sinh ny, nhiu t cu cng th (tr t cu-khng-methicillin). Imipenem c ph
chng thc s ni bt li nhiu vi khun gram m hiu kh bao gm trc khun m xanh v
nhiu chng Enterobacteriaceae khng- cao, nh l loi Enterobacter v Citrobacter. Ph
ni tri bao trm cc vi khun k kh v mt trong nhng khng sinh c tc dng trong iu
tr nhim trng gy ra bi nhng vi khun ny. Tuy nhin, ging nh hu ht cc khng sinh,
chng khng c tc dng trn C.difficile.
Meropenem
Cu trc ca meropenem khc so vi imipenem ti nhnh R1 v R2 (Hnh 5-16). im quan
trng l trong khi imipenem thiu nhnh R1, meropenem li c nhm methyl ti v tr ny
lm cho phn t bn vi s ph hy bi dehydropeptidase thn.
37
Kt qu l, meropenem khng cn s dng km vi cilastatin.Ph hot ng ca meropenem
th tng t nh l imipenem. Do , cc khng sinh ny c ph chng li ni tri trn vi
khun gram dng hiu kh, vi khun gram m hiu kh, vi khun k kh.
Doripenem
Doripenem l mt carbapenem mi c ph duyt gn y. Ging nh meropenem, chng
c nhm methyl ti v tr R1 (Hnh 5-16), do khng b ph hy bi dehydropeptidase
thn. N khc cc carbapenem khc mch nhnh R2 nhng ni chung th tng t ph
hot ng ca imipenem v meropenem. Bng chng invitro ch rng, doripenem c lin
quan lm xut hin t l thp hn cc trc khun m xanh khng thuc hn so vi cc
carbapenem khc, mc d ngha lm sng ca s pht hin ny vn cn cha r rng.
Ertapenem
Ertaenem cng c nhm methyl ti R1 (Hnh 5-16) v do n khng b phn hy bi
dehydropeptidase thn. N khc vi imipenem, meropenem v doripenem ti mch nhnh
R2, do to nn tnh khng khun v tnh cht dc l c mt cht khc bit. Tc dng ca
n yu hn trn cc vi khun hiu kh gram dng, trc khun m xanh v Acinetobacter
spp so cc carbapenem khc. Nhng b li vi nhc im ny th n c u im l dng
liu mt ln mt ngy (cc carbapenem khc phi dng nhiu ln mt ngy).
c tnh
S dng carbapenem th lin quan ti mt vi tc dng khng mong mun, bao gm nn v
bun nn, tiu chy, st, pht ban. Bin chng ng lo lng lin quan n carbapenem l co
git. Bnh nhn ng thi c bnh trn h thng thn kinh trung ng v suy gim chc
nng thn c nguy c cao nht xy ra bin chng ny v nn c s dng thuc mt cch
thn trng. Ban u, meropenem c cho l t gy ra co git hn imipenem, nhng hin nay
nhn nh ny vn ang gy tranh ci. Kt qu ca th nghim trn ng vt ch ra rng
doripenem th t gy ra co git hn l cc carbapenem khc.
Tm li, cc carbapenem c ph tc dng rng ni tri bao gm vi khun hiu kh gram
dng, vi khun hiu kh gram m v hu ht cc vi khun k kh. Kt qu l cc cht ny l
mt trong nhng khng sinh dit khun mnh nht hin nay cn s dng.
im quan trng
Cc chng ca Enterococcus faecalis cn nhy cm vi penicillin th cng nhy cm vi
carbapenem (ngoi tr eratapenem). Tuy nhin Enterococcus faecium li khng tt c cc
carbapenem.
CU HI
22. Imipenem c thy phn bi dehydropeptidase I thn, do phi c phi hp vi
23. Carbapenems c hot tnh ni tri tr hiu kh, hiu kh v

24. So vi cc carbapenem khc, ertapenem t c tc dng dit vi khun hiu kh gram
dng, v
NHM MONOBACTAM
Rt nhiu cc khng sinh -lactam mi c ph dit khun m rt rng, nhng cc
monabactams li theo xu hng tri ngc. Aztreonam, l mt sn phm c thng mi
ha, ch tp trung dit mt loi vi khun nhng n li dit kh l tt: Thuc c th dit vi
khun gram m hiu kh. N ch c dng ng tim duy nht.
Thut ng monobactam c s dng m t mt s thuc khng sinh do nhiu vi sinh vt

sn sinh ch c mt vng lactam n c tri ngc vi cc cu trc hai vng lin kt ca
cc penicilin, cephalosporin, v carbapenems (Hnh. 5-17). Aztreonam l mt monobactam
tng hp kt hp mt s tnh nng hu ch ca ca -lactam khc.
Hnh 5-17. Cu trc ca aztreonam. Chui R1 tng t vi ceftazidime.
V d mt chui nhnh trong cu trc ca azetreonam dng nhm aminothiazolyl gip ci

thin ng k tc dng trn cc vi khun hiu kh gram m ca cephalosporin th h 3 (so
snh Hnh. 5-17 viHnh. 5-13 trong phn tho lun "Cephalosporins").
Nh kt qu ca vic thit k cng thc, aztreonam tip cn v kt ni kh tt vi cc PBPs

ca cc vi khun gram m hiu kh v n vn bn vng khng li rt nhiu -lactamase
c tit ra bi nhng chng ny (Bng 5-17). Khng sinh ny c tc dng tt trn Neisseria
v Haemophilus spp. v c tc dng trung bnh trn P. aeruginosa. Tht khng may,
39
azetronam khng lin kt vi PBPs ca cc vi khun gram dng hoc k kh v do
khng hn l hu ch cho cc bnh nhim trng gy ra bi cc chng vi khun ny.
khng vi aztreonam xy ra trn mt s chng ca Enterobacteriaceae v P. aeruginosa,
thng l kt qu ca nhng thay i trong tnh thm ca mng ngoi ca cc vi khun hoc
tit cc lactamases phn hy thuc.
c tnh
Mt trong nhng li th ln ca aztreonam l tnh an ton ca n. Thuc khng c c tnh

lin quan n thn v c th c xem nh l mt la chn thay th cho cc aminoglycosid,
v c hai u c tc dng trn vi khun gram m hiu kh. Quan trng hn, khng c d ng
cho gia aztreonam v cc -lactams khc, v vy aztreonam c xem l an ton khi s
dng trn nhng bnh nhn b d ng vi penicillin.
Tm li, aztreonam l khng sinh duy nht thuc nhm monobactam c thng mi
ha, c tc dng rt tt trn vi khun gram m hiu kh nhng khng phi l la chn tt i
vi vi khun gram dng hoc vi khun k kh. y l mt loi thuc tng i an ton v
c th c s dng cho cc trng hp d ng vi cc -lactam khc.
CU HI
25. l khng sinh monobactam duy nht c sn trn th trng.
26. Aztreonam c tc dng rt tt chng li cc vi khun hiu kh nhng li c tc dng

km trn vi khun hiu kh v vi khun
27. Mt c im c bit hu ch ca aztreonam l n c th c s dng nhng bnh

nhn b d ng vi cc khng sinh khc.
NHM GLYCOPEPTIDES:
Nhm khng sinh glycopeptide l cc peptide gn vi cc gc ng. Vancomycin v

telavancin l hai thuc thuc nhm ny. Glycopeptide dng nguyn vn c hp thu km
ng tiu ha, do , cc thuc ny phi c tim tnh mch iu tr cc bnh nhim
trng. So vi cc khng sinh khc, chng c cu trc phc tp v trng lng rt ln (Hnh
5-18), do lm ngn cn chng i qua knh porins mng ngoi ca vi khun gram m.
Nh vy, hot ng ca chng ch c tc dng trn cc vi khun gram dng (Bng 5-18).
Tuy nhin, phm vi bao trm ca chng trn cc chng gram dng kh l n tng.
Vancomycin v telavancin c tc dng chng li gn nh tt c cc loi t cu v lin cu,
bao gm c t cu vng khng methicillin v chng ph cu khng penicilin. Tnh nhy cm
trong nhm enterococci by gi khc nhau. Mc d L. monocytogenes thng xut hin
nhy cm in vitro, trn lm sng mt s iu tr tht bi c bo co vi vancomycin, v
cc khng sinh ny khng nn c s dng
Hnh 5-18. Cu trc ca nhm glycopeptides. A. Vancomycin. B. Telavancin. Chui khoanh

trn ca telavancin l thn du.
41
iu tr nhim trng gy ra bi tc nhn ny. Nhm glycopeptide cng c hot ng tt i
vi vi khun k kh Gram dng, bao gm C. difficile.
Ging nh cc -lactams, cc glycopeptide dit vi khun bng cch ngn chn s tng hp
ca cc vch t bo vi khun. Chng lin kt vi cc phn d-alanyl-d-alanine ca chui
peptide dng tin cht ca cc tiu n v peptidoglycan. Bi v phn ln cc glycopeptide
phn t ln, lin kt ny ngn cc tiu n v tip cn vi cc PBPs m thng thng s kt
hp chng vo cc chui polymer peptidoglycan ang c hnh thnh (Hnh. 5-19A).
Mt s vi khun pht trin mt cch tinh vi chng li glycopeptide. Nhng vi khun

ny m ha gen thay i cu trc ca tin cht peptidoglycan v d nh cc on dipeptit d-
alanyl-d-alanine c thay i, thng l d-alanyl-d-lactate (Hnh. 5-19B). Glycopeptide
khng cn kh nng nhn ra v lin kt vi nhng tin cht ca chui peptidoglican. Mt
iu khng mong mun l cc cm gen m ha hot ng ny trong enterococci c th
chuyn nhng cho nhau v c tm thy trong S. aureus. Do , ngi ta d on
khng glycopeptide cng s xy ra vi tn s ngy cng tng trong chng t cu
staphylococci.
Lch s
Vancomycin c pht hin khi mt nh truyn gio t Borneo gi mu t mt ngi

bn ca ng l mt nh khoa hc ha hu c ti Eli Lilly and Company. Cc mu t
nui dng mt loi sinh vt sn sinh ra mt hp cht c hot tnh mnh chng li vi khun
gram dng. Cui cng cc hp cht ny c phn lp tinh khit v t tn l vancomycin,
c ngun gc t ch "vanquish - nh bi".
Hnh 5-19. A. Vancomycin lin kt vi cc dipeptit d-alanyl-d-alanine pha peptide

ca chui tiu n v peptidoglycan mi c tng hp, ngn nga chng gn vo vch t
bo bi cc protein gn penicilin (PBPs). B. Trong nhiu chng enterococci khng
vancomycin, dipeptit d-alanyl-d-alanine c thay th bng d-alanyl-d-lactate m
vancomycin khng th nhn bit c. Do , cc tiu n v peptidoglycan c kt hp
mt cch thch hp vo vch t bo.
Vancomycin
Vancomycin l khng sinh thng c s dng nht ca nhm ny (xem Hnh. 5-18A).
y l mt loi thuc c ban u c xem l c c tnh ng k. Tuy nhin, c tnh ny,
by gi l c bit n l do cc cht tp bi hu qu ca qu trnh lm tinh khit khng
tt. K thut sn xut mi tng cng rt nhiu cc c tnh an ton ca vancomycin,
trong khi cc khng sinh khc, chng hn nh cc penicillin, dn dn hn ch phm vi s
dng ca chng do tnh trng tng khng. Kt qu l, vancomycin tr thnh mt trong
nhng khng sinh bn vng v ng mt vai tr quan trng trong iu tr. Tuy nhin, vi s
gia tng s dng, v tr u vit ca n, b e da bi cc chng khng thuc mi xut
hin, c bit l cc enterococci. Mc d vancomycin thng tim tnh mch, khng sinh
ny vn c th c a qua ng ung iu tr nhim trng ng rut, chng hn
nhtiu chy do C. difficile, nhng n s khng c hp thu khi dng theo ng dng ny.
Telavancin
Telavancin l mt dn xut c pht trin gn y ca vancomycin, c gn thm mt
chui bn decylaminoethyl lipophilic vo li peptide, trong phn loi n nh l mt
lipoglycopeptide (xem Hnh. 5-18B). Dng thay th ny tng cng lin kt vi d-alanine-d-
alanine trong giai on trung gian to peptidoglycan so vi vancomycin nn telavancin s c
kh nng ln hn c ch s tng hp peptidoglycan. Cc chui bn lipophilic cng pht
huy kh nng lin kt vi mng t bo vi khun, c th dn n mt mng, hnh thnh l
43
thng, v lm thot ra cc cht bn trong. Nh vy, telavancin c hai phng thc khng
khun v, v mt l thuyt, c th mnh hn vancomycin, mc d cn nhiu nghin cu
xc nhn iu ny. Telavancin c chp thun cho iu tr cc bnh nhim trng da v cu
trc da phc tp.
c tnh
Vancomycin c th gy mt thnh gic, c bit khi dng cng vi amynoglycosid. Truyn
tnh mch nhanh c th gy nn phn ng ni mn (hi chng red man), bnh nhn c
th b nga v pht ban mt, c v thn trn. Hi chng ny khng phi l mt phn
ng d ng m c th trnh khi bng cch truyn vi mt tc chm hn. Trng hp
him hn, gim bch cu c th xy ra khi s dng nhm khng sinh ny. Televancin c nh
hng lin quan n h thng thn kinh (mt ng, ri lon tm thn, nhc u), hi chng
tiu ha (nn, bun nn, c v kim loi).
Tm li, nhm khng sinh glycoglycosid c tc dng dit khun mnh trn vi khun hiu
kh v k kh Gram dng. Mc d hin tng khng khng sinh ang tng cao, nhng
nhm khng sinh ny vn s l cha kha trong phc iu tr hin nay cng nh trong
nhiu nm ti.
CU HI:
28. Glycopeptides c tc dng dit khun mnh trn c vi khun.hiu kh v k kh.
29. Gn y, vic khng khng sinh vancomycin tr nn ph bin hn trn chng vi
khun
30. Ging nh nhm vi khun -lactam, glycopeptides dit vi khun bng cch ngn khng
cho qu trnh tng hp
31. Khng ging nh vancomycin, telavancin s hu mt chui bn a lipid, c phn loi
n nh mt
Daptomycin
Daptomycin l mt khng sinh c mt vng lypopeptid c ph duyt s dng M t
nm 2003 (Hnh 5-20). Phn lipid ca phn t thuc m qua mng t bo cht ca vi khun,
to thnh mt knh ion dn in, lm cho cc ion trong vi khun thot ra ngoi dn n s
ph hy ca vi khun. Daptomycin c tc dng chng li rt nhiu vi khun Gram dng,
bao gm c nhiu chng khng thuc quan trng nh MRSA, ph cu khng penicillin, v c
enterococci khng li vancomycin. Daptomycin khng c tc dng trn cc vi khun Gram
m v n khng th xm nhp qua mng ngoi ca vi khun Gram m tip xc vi mng
sinh cht. Nhc im ca Daptomycin l khng c tc dng trn phi v khng c ch
nh cho iu tr vim phi. Khng sinh ny mi c lm nghin cu vi tc dng trn
nhim khun da v m mm. Dng ng dng ung th khng c sn.
c tnh
Daptomycin c dung np kh l tt, nhng c th khng dung np cng c quan st

trng hp liu dng cao hn. Vim tnh mch, pht ban v cc tc dng c hi trn tiu ha
c th xut hin.
Tm li, Daptomycin c ha hn nh l mt tc nhn chng li cc vi khun Gram

dng, nhng vn cn thm cc th nghim lm sng khng nh hiu qu trong iu tr
cc bnh khc ngoi nhim khun da v m mm.
CU HI
32. Cu trc ca Daptomycin l mt
33. Daptomycin c tc dng tt trn vi khunhiu kh.
45
Colistin
Sau khi c a vo s dng ln u tin vo nm 1950, th khng sinh ny gp phi s
phn i v b rt ra khi th trng vo nm 1980 bi c tnh trn kh nng nhn thc
cng nh c nhiu khng sinh khc la chn hn ti thi im y. Tuy nhin, trong
nhng nm gn y, coliscin li tr thnh mt la chn kh ph bin khi m cc nh thc
hnh lm sng phi i mt vi vic gim s la chn trong iu tr bi tnh a khng thuc
ca cc chng vi khun Gram m.
Coliscin l khng sinh thuc nhm polymyxin. l mt vng cation 12 peptide vi mt

chui acid bo (Hnh 5-21). u dng cho php coliscin lin kt vi cc phn t tch in
m lipopolysaccharide trong mng ngoi ca vi khun, lm dch chuyn cc ion Ca++ v
Mg++ bnh thng lm n nh cc lipid ny. ui axit bo to iu kin chn colistin vo
mng ngoi. S cng knh ca colistin lm ph v cc lin kt cht ch ca cc phn t
lipopolysaccharide,
dn n tng tnh thm v cui cng l s ly gii ca vi khun. khng xy ra bi mt s

c ch, v d nh s thay i u m lin quan n lipopolysaccharide, do lm gim s
tng tc gia colistin v lipopolysaccharide. Nh d kin, colistin ctc dng chng li
nhiu vi khun hiu kh gram m, bao gm c P. aeruginosa, E. coli,v Klebsiella spp.
(Bng 5-20). Bi v colistin khng b s dng thng xuyn nhiu thp k qua, nhiu
chng a khng thuc ca cc vi khun cn nhy cm vi n. Colistin khng c tc dng
trn mt s vi khun Gram m (v d, Proteus vSerratia spp.), vi khun gram dng, v vi
khun k kh.
c tnh
c tnh ca coliscin, m trc y l nguyn nhn dn n vic rt ra khi th trng ca
n, hin nay c nhn thy l t c hn ngi ta tng. Tuy nhin, n c lin quan gy
c thn (gim thanh thi creatinin) v nhim c thn kinh (v d, chng mt, suy
nhc, mt iu ha, d cm, chng mt).
Tm li, colistin c tc dng trn nhiu vi khun hiu kh Gram m v rt hu dng trong
vic iu tr bnh nhim khun c nguyn nhn bi cc vi khun m khng nhiu khng
sinh hin nay ang dng.
CU HI
34. Colistin lin kt v ph hy trong mng ngoi ca t bo vi khun.
35. Colistin c tc dng chng li cc vi khun hiu kh
47
Chng 6: Khng sinh bt hot s sn xut protein
H v tn: Nguyn Th Hng M. SV_H Dc H Ni
Hiu nh: DS. V Th H
Vi khun phi lin tc s dng cc ngun sn c trong mi trng ca chng sn xut cc

phn t mi thay th nhng phn t trc v hnh thnh cc vi khun mi. V d, protein
mi tip tc c sn xut trong mt quy trnh lin quan n s tng hp mRNA t cc gen
DNA (phin m) v to cc protein t cc mu mRNA ny (dch m). Bi v cc qu trnh
ny l rt quan trng cho s tng trng v nhn ln ca vi khun, chng c th l mc tiu
tn cng bi khng sinh. Trong phn di y, chng ti tho lun v cc tc nhn khng
khun bng cch c ch phin m v dch m ca vi khun.
Nhm rifamycin
Cc rifamycin l thuc khng sinh "ph kin". Cng ging nh mt chic v thi trang hay
vng c lp lnh c s dng t im cho mt chic vy, cc thuc khng sinh ny c
b sung vo cc iu tr truyn thng nhm t hiu qu ti u. Cc rifamycin gm
rifampin (cn gi l rifampicin), rifabutin, rifapentine, v rifaximin (Bng 6-1). Mi cht
c mt cu trc tng t gm mt nhn thm lin kt c hai u bi mt nhnh thn lipid
(Hnh. 6-1).
Cc rifamycin tc dng bng cch c ch RNA polymerase ca vi khun. Chng lm t

trong chui DNA/RNA m ha enzyme ny, v mt khi kt v tr ny, s ko di chui
khng gian ca phn t mRNA mi s b kt. S khng khng sinh pht trin tng i
d dng v c th l kt qu ca mt t bin n l trong gen ca vi khun m ha RNA
polymerase. Nhng t bin ny ch cn thay i mt axit amin n ni m cc rifamycin
lin kt vi RNA polymerase cng ngn lin kt ny. Bi v nhng t bin n l
dn n khng, cc rifamycin thng c s dng kt hp vi cc thuc khc
ngn chn s xut hin cc chng khng thuc.
Nhiu thuc trong s cc rifamycin thng c s dng trong cc phc kt hp iu

tr cc bnh nhim trng mycobacteria (Bng 6-2). Trong s nhng rifamycin, rifampin
c s dng cng vi cc khng sinh khc iu tr nhim trng do t cu. Rifampin
cng c hiu qu nh n tr liu phng nga Neisseria meningitidis v Haemophilus
influenzae. Vic s dng rifampin n c trong d phng ny c ng h bi thc t rng,
thng thng, rt t vi khun c mt khi bnh nhn khng b bnh, do gim thiu c hi
m mt t bin khng rifampin s xy ra mt cch ngu nhin.
Rifampin
Rifampin c s dng lu i nht v rng ri nht trong s cc rifamycin. N cng l cht
cm ng h cytochrome P-450 mnh nht.
Rifabutin
Rifabutin c a chung hn rifampin nhng ngi ng thi c iu tr bnh lao v
nhim HIV v n c ch h cytochrome P-450 mc thp hn so vi rifampin hoc
rifapentine v do c th c dng cng vi nhiu thuc khng retrovirus vn cng tng
tc vi h CYP P450 ny.
Bng 6-1 Cc Rifamycin

Nhng thuc dng ng tim Thuc dng ng ung
Rifampin Rifampin
Rifabutin
Rifapentine
Rifaximin
Hnh 6-1. Cu trc ca rifampin

Rifapentine
Rifapentine c thi gian bn thi di, iu ny dn n vic s dng n trong cc phc
mt ln mt tun cho nhng bnh nhn min dch vi bnh lao.
Rifaximin
Rifaximin l mt rifamycin hp th km c s dng iu tr tiu chy du lch. Bi v n
khng c hp thu ton thn, nn n c tc dng hn ch chng li vi khun xm nhp,
chng hn nh Salmonella v Campylobacter spp.
c tnh
49
Cc rifamycin l thuc gy cm ng mnh h cytochrome P-450. V vy, chng c th nh
hng ng k n nhng thuc chuyn ha bi h CYP ny. Cc Rifamycin cng thng
gy ra ri lon tiu ha nh bun nn, nn, tiu chy v c lin quan n vim gan. Pht ban
da v nhng bt thng v huyt hc cng c th xy ra. ng ch , rifampin gy ra s i
mu da cam-mu ca nc mt, nc tiu, v cc cht lng khc ca c th, c th dn
n s lo lng ca bnh nhn v xn mu knh p trng. Rifabutin c lin quan gy vim
mng gic mc.
Cc rifamycin c s dng ch yu l cc thnh phn ca phc a thuc tr nhim

mycobacteria v mt s nhim trng do t cu. S d dng b vi khun pht trin khng
vi cc cht ny ngn cn vic s dng chng nh n tr liu trong bnh ang hot ng.
CU HI
1. Rifampin gn vica bi khun v c ch tng hp 2. Rifampin c dng ch
yu iu tr bnh gy biv
3. Cc rifamycin thng c dng phi hp vi cc khng sinh khc bi v.vi
cc rifamycin d pht trin khi dng n tr liu.
c thm
Burman WJ, Gallicano K, Peloquin C. Comparative pharmacokinetics and
pharmacodynamics of the rifamycin antibacterials. Clin Pharmacokinet. 2001;40:327341.
Campbell EA, Korzheva N, Mustaev A, et al. Structural mechanism for rifampicin
inhibition of bacterial RNA polymerase. Cell. 2001;104:901912. Huang DB, DuPont HL.
Rifaximina novel antimicrobial for enteric infections. J Infect. 2005;50: 97106.
Munsiff SS, Kambili C, Ahuja SD. Rifapentine for the treatment of pulmonary
tuberculosis. Clin Infect Dis. 2006;43:14681475.
Nhm Aminoglycoside
Cc aminoglycosid l mt trong cc loi thuc khng sinh lu i nht, bt u t khi phn
lp streptomycin t vi khun Streptomyces griseus vo nm 1944. Neomycin xut hin nm
1949, tip theo l gentamicin nm 1963, tobramycin nm 1967, v amikacin nm 1972
(Bng 6-3). Ging nh penicillin, cc thuc ny ban u l tc dng chng c vi khun gram
m v gram dng. Tuy nhin, khng ging nh penicillin, cc aminoglycosid vn duy tr
hiu qu ca chng chng li rt nhiu nhng vi khun mc d hn 30 nm s dng v ngy
nay l khng sinh c dng ph bin.
Cc khng sinh nhm aminoglycoside l nhng phn t tch in dng c kch thc kh
ln (Hnh. 6-2), mc d vn ch bng mt phn ba kch thc ca vancomycin. Mi phn t
aminoglycoside bao gm hai hoc nhiu ng lin kt bi mt lin kt glycoside vi mt
vng su cnh trung tm c cha nhm th nhm amin. Tn aminoglycoside c ngun gc
t cc nhm amin v cc lin kt glycoside. Khng ging nh vancomycin, cc
aminoglycosid c tc dng chng li vi khun gram m hiu kh tuyt vi bi v kch thc
ca chng khng ngn cn chng i qua mng ngoi vi khun. Thay vo , tnh cht tch
in dng ca aminoglycoside cho php chng bm vo cc mng ngoi tch in m v
kt qu l hnh thnh cc l thong qua cc phn t khng sinh di chuyn, xm nhp vo
cc ribosome ca vi khun, l mc tiu ca cc aminoglycoside, do i hi s thm
nhp qua cc mng t bo cht ca vi khun. iu ny c thc hin bi mt c ch vn
chuyn tch cc trong vi khun ph thuc nng lng m yu cu c oxy v mt lc thc
y proton hot ng. V nhng l do ny, cc aminoglycoside tc dng km trong mi
trng k kh v c tnh axit nh p xe v khng c tc dng chng li cc vi khun k kh.
Mi aminoglycoside hot ng bng cch gn vo tiu n v 30S ca ribosom vi khun,
gy ra s gn nhm gia mRNA codon v aminoacyl-tRNA. iu ny s thc y dch m
sai protein.
V nhng l do khng r, khng vi khng sinh aminoglycoside vn cn kh him. Khi

n xy ra, n thng l kt qu ca mt trong ba c ch (Hnh 6-3.): (1) gim tch ly thuc
bn trong cc loi vi khun, trong nhiu kh nng do s c mt ca bm tng thuc ra
ngoi; (2) cc enzym vi khun nh acetyltransferase, nucleotidyltransferase, v
phosphotransferase lm bin i thuc v ngn cn n gn vo ribosome; v (3) s t bin
ca cc ribosome ca vi khun lm cho cc aminoglycoside khng cn lin kt vi n. (C
ch mi ny dng nh kh him.) khng khng phi lun ng vi tt c cc thuc
trong nhm. V d, v chui bn c o, amikacin khng b bin i bi mt s enzym ca
vi khun vn phn hy gentamicin v tobramycin (Hnh 6-2).
Bng 6-3 Cc Aminoglycoside
Thuc dng ngoi ng rut Thuc dng ng ung
Streptomycin Neomycin*
Gentamicin
Tobramycin
Amikacin
51
* Khng hp thu khi ung. c s dng cho nhim khun ng rut.
Hnh 6-2. Cu trc ca amikacin. c im ca cc aminoglycoside gm nhiu ng

amino (B, C) lin kt bi lin kt glycoside vi vng 6 cnh (A) c nhm th amino.
Cc aminoglycoside c tc dng tt chng li vi khun gram m hiu kh (Bng 6-4). Nhng

tc nhn ny thng c s dng iu tr cc nhim khun do Enterobacteria v
Pseudomonas aeruginosa. Bi v kt qu tht vng trn nghin cu ng vt, cc
aminoglycoside thng c s dng kt hp vi mt tc nhn c tc dng khc, thm ch
chng li cc chng vi khun nhy cm cao vi aminoglycoside. Cc tc nhn ny tc
dng trn vi khun Gram dng hiu kh km hn. Hiu qu ca cc aminoglycoside c
tng cng bi khng sinh c ch tng hp vch t bo vi khun, chng hn nh cc -
lactam v vancomycin. Nh vy, vi mt s vi khun Gram dng hiu kh nh enterococci,
cc aminoglycosid c tc dng hip ng khi c s dng vi cc tc nhn khc ngay c
khi vi khun khng aminoglycoside mc trung bnh. Liu thp cc aminoglycoside, c
gi l liu hip ng, c dng khi chng c s dng vi cc tc nhn c tc dng trn
vch t bo iu tr vi khun hiu kh Gram dng. Mt s cc aminoglycosid cng c tc
dng trn loi Mycobacteria nh Mycobacterium tuberculosis v phc hp Mycobacterium
avium.
Hnh 6-3. khng ca vi khun vi cc aminoglycoside xy ra thng qua mt trong ba c

ch ngn cn s gn bnh thng ca khng sinh vo ch ribosome ca n: (1) Bm tng
thuc ngn s hp thu ca aminoglycoside vo bo tng vi khun. (2) S bin i
aminoglycoside ngn gn vi ribosome. (3) S t bin ca ribosome ngn s gn vi
aminoglycoside.
Streptomycin
Streptomycin l aminoglycoside lu i nht v him khi c s dng ngy nay. N
vn cn l mt thuc hng th hai trong iu tr bnh lao. Ngoi ra, do s khc bit trong c
ch khng, streptomycin vn c hiu lc i vi mt s chng Enterococcus khng vi
tc dng hip ng ca gentamicin v cc aminoglycosid khc.
Gentamicin
Gentamicin c s dng ph bin nht trong cc aminoglycosid. N c tc dng
chng c vi khun gram dng v gram m hiu kh.
Tobramycin
i vi cc mc ch thc hnh, tobramycin c ph tc dng nh gentamicin v
c s dng tng t. Nhn chung, hu ht cc chng khng gentamicin cng t nhy cm
vi tobramycin. Tuy nhin, khng ging nh gentamicin, tobramycin tc dng km trn
Enterococci v khng nn c s dng cho cc bnh nhim khun do vi khun ny.
GHI NH
Khng ging nh tobramycin, neomycin, v streptomycin; gentamicin c nh vn khng
c "y" m l I. iu ny dn n n l mt trong nhng t thng sai chnh t trong y
khoa.
Amikacin
Cc chng vi khun gram m hiu kh c kh nng khng gentamicin v tobramycin
c th vn cn nhy cm vi amikacin. Do , thuc ny c tc dng tng th tt hn chng
li cc vi khun. Tuy nhin, ging nh tobramycin, amikacin t c tc dng chng li
enterococci trn lm sng.
c tnh
Yu t chnh hn ch vic s dng cc khng sinh nhm aminoglycoside l c tnh
ca chng. Cc thuc c lin quan n mc tng i cao c tnh trn thn v tai.
Aminoglycoside thm nhp vo t bo ngi km ngoi tr cc t bo ng ln gn, ni
chng c tp trung. Kt qu l, khong 5% n 10% bnh nhn s dng aminoglycoside
s c c thn hoc suy gim chc nng thn. T l ny c th cao n 50% nhng bnh
nhn c yu t nguy c, chng hn nh tui cao v tip xc ng thi vi cht c thn
53
khc. May mn thay, nhng tn thng thn thng hi phc, v chc nng thn thng tr
li bnh thng sau khi ngng thuc. Lu rng c tnh thn thng ch c quan st thy
sau 4-5 ngy iu tr, v vy cc aminoglycosid c th an ton khi s dng mt thi gian
ngn bnh nhn khng c nguy c cao vi tc dng ph ny. c tnh trn tai bao gm
hai loi: suy gim thnh gic, c th dn n ic, v c tnh tin nh, kt qu l ri lon
cn bng. Streptomycin c lin quan vi t l cao c tnh tin nh.
Cc aminoglycosid vn l cc thuc mnh iu tr nhiu bnh nhim khun do vi
khun gram m hiu kh. Chng cng tc dng hip ng vi cc thuc tc dng trn vch t
bo v c ch nh mt liu php b tr chng li mt s vi khun hiu kh gram dng.
c tnh vn l mi quan tm khi s dng ca chng.
CU HI
4. Cc aminoglycosides c tc dng mnh trn vi khunhiu kh.
5. Cc aminoglycosides c dng vi liu hip lc cng vi thuc tc dng trn
vch t bo iu tr mt s chng vi khun.hiu kh.
6. Hai c tnh lin quan n dng cc aminoglycoside lv
C THM
Chambers HF. Aminoglycosides. In: Burunton LL, Lazo JS, Parker KL, eds. Goodman and
Gilmans the Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-
Hill; 2006:11551172.
Gonzalez LS III, Spencer JP. Aminoglycosides: a practical review. Am Fam Physician.
1998;58: 18111820.
Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM. Aminoglycosides: activity and
resistance. Antimicrob Agents Chemother. 1999;43:727737.
Vakulenko SB, Mobashery S. Versatility of aminoglycosides and prospects for the future.
Clin Microbiol Rev. 2003;16:430450.
Nhm macrolide v ketolide

Khng sinh nhm macrolid l nhm c tc dng trn nhiu loi vi khun, nhng khng mnh
trn ring loi no. Cc macrolide c tc dng chng li mt s vi khun gram dng, mt
s vi khun gram m, mt s vi khun khng in hnh, mt s mycobacteria, v thm ch
mt s xon khun. Nhng chng khng c hiu qu tin cy chng li hu ht cc vi khun
trong bt k mt nhm no. Tuy nhin, chng vn l cc thuc rt hu ch cho vic iu tr
cc loi nhim khun c th, chng hn nh nhim khun ng h hp, v iu tr trc
tip mt vi loi c th. Cc khng sinh nhm macrolide bao gm erythromycin,
clarithromycin, v azithromycin (Bng 6-5). Telithromycin l thuc gn y c ph
duyt vo nhm khng sinh c cu trc lin quan gi l nhm ketolide v cng s c tho
lun y.
Tt c cc macrolide gm mt li l mt vng ln c gi l vng lacton macrocyclic

(Hnh. 6-4) (do c tn nhm l macrolid). Vng ny c gn vi ng. Macrolide gn
cht vi tiu n v 50S ca ribosom vi khun v tr chn cc li ra ca cc peptide
c tng hp mi. Nh vy, chc nng ca cc macrolide tng t nh cc aminoglycosid
trong nhm mc tiu l ribosome v ngn cn s tng hp protein. S khng ngy
cng tr nn ph bin v xy ra bi mt trong nhiu c ch: (1) s c ch thuc thm nhp
v tch ly - macrolide kh thm nhp vo mng ngoi ca hu ht cc trc khun gram m
hiu kh v b tng ra khi mt s vi khun khng thuc mt cch tch cc. V d, mt s vi
khun Gram dng nh Streptococcus pneumoniae, cha mt gen MEF m ha bm tng
thuc lm gim s tch ly ca macrolide trong vi khun. (2) s thay i v tr gn ribosome
qua trung gian enzyme - mt s vi khun khng macrolide bng cch methyl ha phn
ribosome 50S thng c gn bi cc loi thuc, ngn nga s tng tc ny. V d, loi
khng ny c m ha bi gen erm trong S. pneumoniae. Methyl ha ribosome theo cch
ny cng c dn n khng clindamycin v cc streptogramin, m tc dng bng cch gn
ribosome ca vi khun v ngn cn dch m protein. (3) t bin v tr gn ribosome - him
khi xy ra, t bin xy ra nh hng n cc phn ca ribosome ca vi khun gn vi
macrolide. Bt k c ch no, s khng mt thuc ca nhm macrolid thng ng khng
vi tt c cc thuc trong nhm.
L mt nhm, cc macrolide c tc dng vi cc vi khun khc nhau (Bng 6-6). Chng c

hiu qu i vi mt s chng t cu v lin cu, mc d thng khng c tc dng trn t
cu khng methicillin v lin cu khng penicillin. Nhc im chnh trong ph tc dng
ca macrolide l hu ht cc trc khun gram m hiu kh u khng, nhng mt s chng
Neisseria, Bordetella, v Haemophilus nhy cm. Cc macrolide khng c hiu qu trong
vic iu tr hu ht cc nhim khun k kh. Nhng chng c tc dng chng li nhiu vi
khun khng in hnh v mt s mycobacteria v xon khun.
55
Bng 6-5 Cc macrolide v ketolide
Thuc dng ngoi ng tiu ha Thuc dng ng ung
Erythromycin Erythromycin
Clarithromycin
Azithromycin Azithromycin
Telithromycin
Hnh 6-4. Cu trc ca erythromycin (bn trn) v telithromycin (pha di). Nhm th
c khoanh trn A v B phn bit telithromycin vi cc macrolide. Nhm th A cho php
telithromycin gn vo v tr th hai ribosome vi khun.
Erythromycin
Erythromycin l macrolide lu nht, c pht hin vo nm 1952 v c mt vng lacton
macrocyclic 14 cnh (Hnh. 6-4). N t hiu qu hn so vi cc macrolid khc trong iu tr
cc bnh nhim khun ng h hp v n t hiu qu trn H.influenzae. Bi v n c ph tc
dng tng t nh clarithromycin v azithromycin nhng dung np km hn nn n c
thay th bng nhng thuc mi.
Clarithromycin
Clarithromycin l mt dn xut bn tng hp ca erythromycin v cng gm mt vng
lacton macrocyclic 14 cnh. N c tc dng chng li cc vi khun Gram dng hiu kh v
H. influenzae hiu qu hn erythromycin.
Azithromycin
Azithromycin c vng lacton macrocyclic 15 cnh linh hot cho php n thm nhp tt hn
vo mng ngoi ca mt s vi khun gram m hiu kh. Do , n phn no tc dng chng
li cc vi khun hiu qu hn v rt hiu qu trong vic iu tr H. influenzae. Mt trong
nhng u im chnh ca n l n c hp thu vi nng cao cc m v sau t t
gii phng t m vo mu trong nhng ngy tip theo. Do , liu trnh 5 ngy dng ng
ung cho kt qu duy tr nng thuc iu tr trong mu trong 10 ngy.
Telithromycin
Telithromycin l thuc thng mi u tin ca mt nhm thuc khng sinh mi gi l
ketolide. Ketolide c cu trc lin quan n cc macrolid (Hnh. 6-4), nhng c ph tc dng
m rng. Telithromycin gn vo cng v tr trn tiu n v 50S ca ribosom vi khun nh
cc macrolide nhng c phn m rng alkylaryl (c ghi "A" trong hnh. 6-4), gn vi mt
v tr ring bit th hai trn ribosome. Hai v tr gn thay v mt dn n s gn cht hn v
tip tc tc dng ngay c khi c mt mt s enzyme gy methyl ha ribosome v gy ra
khng vi cc macrolide. S gn cht hn cng hn ch y telithromycin ra bi bm tng
thuc macrolide. Nh vy, telithromycin c tc dng chng li nhiu chng Streptococcus
pneumoniae, Staphylococcus aureus v Streptococcus pyogenes khng macrolide.
57
Telithromycin c chp nhn cho s dng nhng bnh nhn b nhim trng ng h hp
do vi khun v c nghin cu mt cch cn thn nht vi cc vi khun gy cc bnh
nhim trng ny (Bng 6-7). Trong trng hp ny, n c tc dng chng li hu ht cc
chng S. pneumoniae, k c cc chng khng penicilin v khng nhm macrolid.
Telithromycin cng c tc dng chng li cc chng staphylococci v streptococci khc tt
hn cc macrolide, mc d mt s chng khng do chng c kh nng thay i cc
ribosome theo cch m ngay c telithromycin cng khng cn lin kt c.
Enterobacteriaceae khng telithromycin, nhng H. influenzae v Bordetella pertussis nhy
cm. Cc tc dng ca thuc ny i vi Neisseria spp. cha c nghin cu tt. Nhiu vi
khun khng in hnh nh Chlamydia pneumoniae, Mycoplasma pneumoniae v Legionella
pneumophila nhy cm vi telithromycin, nhng tc dng ca n i vi mycobacteria v
xon khun cha c xc nh. Telithromycin hin ch c sn dng ung.
c tnh
Cc macrolid l nhng thuc an ton, cc phn ng bt li tng i nh. Erythromycin lin
quan vi cc triu chng tiu ha nh bun nn, nn, tiu chy v vim tc tnh mch sau
khi tim tnh mch, nhng clarithromycin v azithromycin thng c dung np kh tt.
Ko di QT dn n nhp tht nhanh a hnh c bo co khi s dng cc thuc ny.
Erythromycin v clarithromycin, tr azithromycin c kh nng c ch cytochrome P-450 v
do nh hng n nng ca cc thuc khc b chuyn ha qua CYP ny.
Telithromycin l mt cht c ch mnh m P-450 v do nh hng n mc nhng
thuc khc c chuyn ha bi h thng CYP ny. Vic s dng n lin quan ti ri lon
tiu ha, nhc u, chng mt, v ko di QT. Ngoi ra, cht ny c th gy ri lon th gic
nh nhn o ngc m, nhn i, hoc tp trung kh khn. ng lo ngi l cc bo co gn
y cho rng n cng c th gy tn thng gan nghim trng.
Cc macrolid c mt s tc dng chng li vi khun gram dng hiu kh, vi khun gram m
hiu kh, vi khun khng in hnh, mycobacteria, v xon khun. Tuy nhin, trong mi
nhm, mt s vi khun khng vi thuc, v macrolide, do , phi c dng thn trng
khi dng theo kinh nghim. Telithromycin l mt thuc thuc nhm thuc khng sinh mi
gi l nhm ketolide c lin quan cu trc vi cc macrolid. N ng ch v tc dng vt
tri ca n trn S. pneumoniae. N c nghin cu ch yu iu tr cc bnh nhn b
vim phi mc phi ti cng ng t nh n trung bnh.
Cu hi
7. Trong cc macrolide, __________ c bao ph trn vi khun gram m mhieeus kh
tt nht nn hu ch tr li ____________ .
8. __________v ____________ l cc macrolides dung np tt hn erythromycin.
9. Cc macrolide c tc dng ngho nn chng li trc khun gram m hiu kh v vi
khun ______________ .
10. Telithromycin l mt thnh phn ca nhm khng sinh __________ .
11. Bi v ph tc dng ca n, telithromycin hu ch nht iu tr cc nhim
khun _________.
c thm
Clark JP, Langston E. Ketolides: a new class of antibacterial agents for treatment of
community- acquired respiratory tract infections in a primary care setting. Mayo Clinic Proc.
2003;78:11131124.
Leclercq R. Mechanisms of resistance to macrolides and lincosamides: nature of the
resistance elements and their clinical implications. Clin Infect Dis. 2002;34:482492.
Lonks JR, Goldmann DA. Telithromycin: a ketolide antibiotic for treatment of
respiratory tract i nfections. Clin Infect Dis. 2005;40:16571664.
Neu HC. New macrolide antibiotics: azithromycin and clarithromycin. Ann Intern
Med. 1992;116: 517519.
Zuckerman JM. The newer macrolides: azithromycin and clarithromycin. Infect Dis
Clin North Am. 2000;14:449462.
59
Nhm Tetracycline v Glycylcycline
Nhm tetracycline l mt nhm cc khng sinh xut hin t nhng nm 1950. Ngy nay, ba
thuc ca nhm ny thng c s dng: tetracycline, doxycycline, v minocycline
(Bng 6-8). Tigecycline, mt thuc thuc nhm glycylcycline c lin quan cu trc vi
nhm tetracycline, gn y c ph duyt cho s dng. Cu trc ct li ca tetracycline
bao gm bn vng 6 cnh hp nht (Hnh. 6-5). Cu trc ny cho php cc tetracycline
tng tc vi cc tiu n v 30S ca ribosom vi khun v ngn cn s gn bi cc phn t
tRNA vi cc axit amin. Bng cch ny, tng hp protein b chn li. khng vi
tetracycline thng xy ra bi mt trong hai c ch. Gen ngoi sinh m ha cho bm tng
thuc, ngn cn s tch ly trong t bo ca cc loi thuc ny. Ngoi ra, c s gp phn ca
gen m ha cc protein bo v ribosome. Nhng yu t lm thay i cu to ca ribosome vi
khun lm tetracycline khng cn gn vo chng c na, do qu trnh dch m protein
khng b nh hng.
Cc tetracycline c tc dng chng li mt s vi khun Gram dng hiu kh, nh S.

pneumoniae, v mt s vi khun gram m hiu kh, nh H. inuenzae v N. meningitidis
(Bng 6-9). Cc thuc ny cng c mt s tc dng trn vi khun k kh v c th c s
dng iu tr nhim khun gy ra bi mt s xon khun, chng hn nh Borrelia
burgdorferi v Treponema pallidum. Tuy nhin, u im ca nhm thuc ny l c tc dng
i vi vi khun khng in hnh, bao gm c Rickettsia, Chlamydiae, v vi khun
Mycoplasma.
Tetracycline
Tetracycline c pht hin nm 1953 nhng vn s dng cho ti nay. N c sn dng
ung.
Doxycycline
Ph tc dng ca doxycycline l c bn ging nh tetracycline. N thng c s dng v
thi gian bn thi di hn, cho php dng liu hai ln mi ngy.
Bng 6-8 Nhm Tetracycline v Glycylcline
Thuc dng ngoi ng rut Thuc dng ng ung
Doxycycline Tetracycline
Tigecycline Doxycycline
Minocycline
Hnh 6-5. Cu trc tetracycline

Minocycline
Ph tc dng ca minocycline tng t nhng tetracycline khc nhng thuc ny thch hp
cho vic iu tr cc bnh nhim khun t cu khng methicillin hn. Minocycline i khi
cng c s dng cho bnh phong do Mycobacterium leprae.
Tigecycline
Tigecycline khng phi mt tetracycline nhng l mt thuc thuc nhm khng sinh c cu
trc lin quan l nhm glycylcycline, trong tigecycline l thuc duy nht c thng
mi ha. S khc bit chnh ca nhm glycylcycline l c thm mt nhm glycyl amide vo
vng su cnh cui cng ca cu trc ct li tetracycline (Hnh. 6-6). Ngoi ra, iu ny
ngn cn s nhn ra ca tigecycline bi cc bm tng thuc ca vi khun v lm cho n vn
c th gn vi ribosom k c khi tiu n v 30S ca ribosome bin i khng li
tetracycline. Bi v c ch ny chim phn ln trong cc c ch khng tetracycline, nhm
tigecycline c ph khng khun rt rng. N c tc dng chng li hu ht cc vi khun
gram m hiu kh, bao gm c vi khun a khng thuc Acinetobacter spp. Tuy nhin, P.
aeruginosa v Proteus spp., sinh ra cc bm tng thuc ny, thng khng vi n (Bng
6-10).
Hnh 6-6. Cu trc ca tigecycline
61
Hu ht cc vi khun Gram dng hiu kh, bao gm c t cu khng methicillin,
enterococci khng vancomycin, v S. pneumoniae khng penicillin, d nhy cm vi
tigecycline. N cng c tc dng tt i vi vi khun k kh, mc d km hn cc
carbapenem v piperacillin-tazobactam. Nh d kin ca thuc lin quan tetracycline,
tigecycline dng nh c tc dng tt chng li cc vi khun khng in hnh.
c tnh
Nhm tetracycline l nhng thuc tng i an ton, nhng mt s chng ch nh cn phi
nh. Mt trong cc iu ct li ca cc thuc ny l gn phc chelate mnh ca cc ion kim
loi nh canxi. iu ny c th dn n lm rng b xm hay vng v nh hng ti s pht
trin xng. i vi nhng l do ny, tetracycline khng nn s dng cho ph n mang thai
v thn trng cho tr em di 8 tui. Phn ng qu mn nh pht ban v sc phn v xy ra
nhng khng ph bin. Mt ngoi l l tng sc t mu xanh-en ca da v nim mc c
quan st tng i thng xuyn vi vic s dng minocycline. Tetracycline cng lin quan
gy phn ng nhy cm nh sng. Tc dng ph trn tiu ha nh bun nn, nn, v lot
thc qun cng c th xy ra, cng nh gy c gan.
Nhm Tetracycline l mt nhm khng sinh c m vn cn c s dng iu tr cc

bnh nhim khun do mt s vi khun nht nh, c bit l vi khun khng in hnh.
Tigecycline thuc nhm glycylcycline l mt dn xut mi ca cc thuc vi hot tnh
rng chng li cc vi khun hiu kh v k kh, bao gm mt s loi khng vi nhiu loi
khng sinh khc. c tnh ca cc thuc ny ngn cn vic s dng ph n c thai v cn
c s dng thn trng tr nh.
Cu hi
12. Nhm Tetracycline c ch s pht trin ca vi khun bng cch gn vi.ca vi khun.
13. Nhm Tetracycline c tc dng tt tr vi khun.
14. Bi v cc vn lm bin i mu ca rng v xng, nhm tetracycline khng nn
dng v nn dng thn trng
15. Tigecycline l mt thnh vin ca nhm khng sinh gi l.
16. Tigecycline c tc dng tr nhiu vi khun.v.hiu kh khng cao..
c thm
Chopra I, Roberts M. Tetracycline antibiotics: mode of action, applications, molecular
biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001;65:232
260. Joshi N, Miller DQ. Doxycycline revisited. Arch Intern Med. 1997;157:14211428.
Livermore DM. Tigecycline: what is it, and where should it be used? J Antimicrob
Chemother. 2005;56:611614. Roberts MC. Tetracycline therapy: update. Clin Infect Dis.
2003;36:462467. Slover CM, Rodvold KA, Danziger LH. Tigecycline: a novel broad-
spectrum antimicrobial. Ann Pharmacother. 2007;41:965972.
Chloramphenicol
Chloramphenicol l mt khng sinh rt c m ln u tin c s dng trn lm sng vo
nm 1947. Mc d vn c hiu qu chng li vi khun khc nhau, c tnh ca n khin
cho vic s dng ca n ch hn ch cho cc trng hp m v chi ph v khng khng
c la chn no khc. Cu trc ca chloramphenicol (Hnh. 6-7) cho php gn vi tiu n
v 50S ca ribosome, ni n ngn cn vic gn ca tRNA vi mt axit amin. khng xy
ra khi vi khun c c gen m ha cho mt enzyme m acetyl ha chloramphenicol, m
ngn cn n gn vi mc tiu ca n. Bm tng thuc nhn ra thuc ny cng c m
t. Chloramphenicol l ch c dng tim ti Hoa K, nhng vin nang ung c sn nhiu
ni khc trn th gii. Chloramphenicol c ph tc dng chng li nhiu loi vi khun khc
nhau (Bng 6-11). N hiu qu chng li nhiu streptococci Gram dng hiu kh, trong
c mt t l cao ca S. pneumoniae v cc chng S. pyogenes. Nhiu vi khun hiu kh gram
m cng nhy cm, k c cc chng H. inuenzae, Neisseria spp., Salmonella spp., v
Shigella spp. Chloramphenicol l mt trong nhng loi thuc khng sinh hiu qu nht
chng li cc vi khun k kh v c th c s dng iu tr nhim khun gy ra bi
Bacteroides fragilis v mt s Clostridium spp. Cui cng, thuc ny c tc dng rt tt
chng li cc vi khun khng in hnh, bao gm Chlamydia trachomatis, M. pneumoniae,
v Rickettsia spp.
c tnh
Khng th tm tt tc dng ca chloramphenicol m khng tho lun c tnh ca n, v n
c tc ng ln v tnh hu ch ca cc thuc ny. Nghim trng nht l nhng nh hng
lin quan n ty xng. Cloramphenicol thng gy c ch ty xng ph thuc vo liu
v tc dng ny c th phc hi trong qu trnh iu tr. c tnh ny c cho l kt qu t
s gn chloramphenicol vi ribosome ti th, ging nh cc ribosome ca vi khun. ng s
hn, nhng rt him gp l s pht trin ca bnh thiu mu bt sn khng th phc hi,
thng xy ra sau khi hon thnh mt liu trnh iu tr. ng nh d on, nhng c tnh
nhanh chng gii hn vic s dng chloramphenicol. Cht ny cng c th dn n t
vong tr s sinh vi hi chng xanh xm v nhng bt thng v thn kinh nh vim dy
thn kinh th gic.
63
Tm li, chloramphenicol c ph tc dng rng bao gm nhiu vi khun Gram dng hiu
kh, Gram m hiu kh, vi khun k kh v vi khun khng in hnh. Vic s dng n, tuy
nhin, b hn ch bi c tnh ca n.
Hnh 6-7. Cu trc ca chloramphenicol
Cu hi
17. Chloramphenicol c chn s pht trin ca vi khun bng cch gn vica vi khun.
18. Chloramphenicol c tc dng tt tr vi khun.v . N cn tc dng trn nhiu vi
khun gram dng hiu kh v gram m hiu kh.
19. khng vi chloramphenicol c th xut hin khi vi khun c kh nng bt hot thuc
bng cch.hoc sn xut.cn tr tch ly thuc.
20. Yu t chnh hn ch vic s dng chloramphenicol lca n, m tc dng ch yu l
c ch.phc hi v .khng phc hi c.
c thm
Feder HM Jr, Osier C, Maderazo EG. Chloramphenicol: a review of its use in clinical
practice. Rev Infect Dis. 1981;3:479491. Trevett AJ, Naraqi S. Saint or sinner? A look at
chloramphenicol. PNG Med J. 1992;35:210216. Wallerstein RO, Condit PK, Kasper CK, et
al. Statewide study of chloramphenicol therapy and fatal aplastic anemia. JAMA.
1969;208:20452050.
Clindamycin
Clindamycin, c gii thiu vo nm 1966, l mt dn xut tng hp ca lincomycin. Cng
vi nhau, cc thuc ny thuc nhm khng sinh lincosamide v c c trng bi cc cu
trc chung ca mt axit amin lin kt vi mt ng amin (Hnh. 6-8). Ch clindamycin,
trong c sn c dng ung v tim tnh mch, thng c s dng ngy nay. Gn y,
c s ti quan tm clindamycin v tc dng chng li nhiu chng S. aureus khng
methicillin cng ng v hiu qu tim tng trong iu tr bnh trung gian qua c t gy
ra bi t cu v lin cu khun.
Cc khng sinh lincosamide gn vi tiu n v 50S ca ribosom vi khun v c ch
tng hp protein. V mt l thuyt, sau , nhng cht ny ngn nga sn sinh c t ca vi
khun, v chng thng c s dng v l do ny nh mt liu php b tr trong hi chng
sc c t do lin cu khun hoc t cu. C ch tc ng ca clindamycin tng t nh ca
cc macrolid. Trong thc t, cc v tr lin kt ca chng chng cho ln nhau. V vy, mt
s chng vi khun c kh nng khng erythromycin v s bin i ribosom cng khng
vi clindamycin. Hu ht cc vi khun gram m khng vi clindamycin v mng ngoi
ca chng chng li s xm nhp ca thuc ny.
Li ch ca clindamycin l tc dng ca n i vi hai nhm vi khun: Vi khun
Gram dng hiu kh v vi khun k kh (Bng 6-12). c bit, n c tc dng chng li
nhiu chng t cu v lin cu, bao gm c mt s chng S. aureus khng methicillin cng
ng. Tng t nh vy, n c ph tc dng chng li cc vi khun k kh tng i rng,
mc d mt s B. fragilis v chng clostridial khng. Nh cp trc , n khng hu
ch i vi cc vi khun Gram m hiu kh.
c tnh
c tnh chnh ca clindamycin, m hn ch vic s dng n, l s xut hin vim
i trng do Clostridium difficile 0.01% n 10% bnh nhn s dng n. Clindamycin tiu
dit nhiu thnh phn ca vi khun bnh thng trong rut, cho php pht trin qu mc ca
C. difficile vn khng thuc ny. dng vim i trng do C. difficile nghim trng nht,
cc mng vn hoi t c thy nm trong i trng, c gi l vim i trng gi mc.
Clindamycin cng lin quan gy tiu chy khng phi do C. difficile v pht ban.
Hnh 6-8. Cu trc ca clindamycin
65
Clindamycin vn l mt thuc hu ch cho vic iu tr mt s bnh nhim khun do
vi khun Gram dng hiu kh v vi khun k kh. N khng c tc dng chng li vi khun
gram m hiu kh. Cn thn trng khi s dng do lin quan n s xut hin tng i
thng xuyn ca vim i trng gi mng do C. difficile.
Lch s
Cc nhm khng sinh lincosamide c t tn t tn a im ni m cc vi khun
sn xut lincomycin c c lp: Lincoln, Nebraska.
Cu hi
21. Clindamycin c tc dng tr nhiu vi khun.hiu kh v vi khun..
22. khng vi.c th dn n khng vi clindamycin mt s chng vi
khun.
23. Dng clindamycin c th gy.nguy him n tnh mng.
c thm
Falagas ME, Gorbach SL. Clindamycin and metronidazole. Med Clin North Am.
1995;79:845867. Fass RJ, Scholand JF, Hodges GR, et al. Clindamycin in the treatment of
serious anaerobic infections. Ann Intern Med. 1973;78:853859. Russell NE, Pachorek RE.
Clindamycin in the treatment of streptococcal and staphylococcal toxic shock syndromes.
Ann Pharmacother. 2000;34:936939. Sutter VL. In vitro susceptibility of anaerobes:
comparison of clindamycin and other antimicrobial agents. J Infect Dis.
1977;135(suppl):S7S12.
Nhm Streptogramin
Trong vi thp k qua, chng ta pht hin ra rng phi hp mt s thuc khng
sinh tng tc dng hip ng dit khun. Tuy nhin, khng bt ng khi chnh vi khun
cng t pht hin ra iu ny trc c chng ta. Streptomyces. spp t nhin tit ra cp
khng sinh thuc nhm streptogramin kt hp vi nhau tiu dit vi khun khc. Tht kh
khn ni cc streptogramin l khng sinh c hay mi. Chng c phn lp nm 1953,
nhng mi n nm 1968, cc thuc u tin ca nhm ny, pristinamycin, mi c
bn trn th trng chu u v phi n nm 1999, mt cp nhm ny, quinupristin /
dalfopristin, mi c mt ti Hoa K. Hin nay, quinupristin / dalfopristin dng tim tnh
mch l streptogramin duy nht c bn Hoa K.
Nhm Streptogramin bao gm hai hp cht macrocyclic khc nhau(Hnh. 6-9), mi
hp cht lin kt vi tiu n v 50S ca ribosom vi khun c ch tng hp protein.
Trong khi , mi hp cht c lp c hot tnh chng vi khun trung bnh, khi phi hp c
hai th tc dng ny mnh ln nhiu. Tc dng hip lc ny c gii thch bi thc t l
mi hp cht ring l c ch mt bc khc nhau trong qu trnh ko di protein v
dalfopristin gy ra s thay i v hnh dng trong ribosome lm tng cng lin kt ca
quinupristin. khng streptogramin xy ra bi ba c ch: s bin i ca cc tiu n v
50S ribosome ngn cn gn streptogramin, bt hot streptogramin bi enzyme, v sn xut
bm tng thuc. Bi v quinupristin v dalfopristin gn vo cng mt vng ca cc ribosome
nh cc macrolides v clindamycin, c ch khng u tin k trn i khi dn n s
khng cho gia ba thuc ny. Quinupristin / dalfopristin c tc dng chng li vi khun
Gram dng hiu kh, k c t cu khng methicillin, S. pneumoniae khng penicilin, v mt
s enterococci khng vancomycin (Bng 6-13). Hu ht cc vi khun Gram dng hiu kh
khc cng nhy cm. Mc d quinupristin / dalfopristin c tc dng in vitro chng li mt s
vi khun gram m hiu kh v mt s vi khun k kh, hiu qu lm sng ca n trong iu
tr cc bnh nhim khun hin nay cha r rng, v khng nn c s dng cho nhng mc
ch ny.
Hnh 6-9: Cu trc ca quinupristin/dalfopristin
67
c tnh
Cc tc dng ph lin quan ti v tr truyn thuc l rt ph bin khi quinupristin /
dalfopristin c dng thng qua mt ng thng tnh mch ngoi bin. Chng bao gm au,
nhim khun, v vim tc tnh mch. V l do ny, thuc ny c khuyn khch dng thng
qua mt ng thng tnh mch trung tm. au khp, au c, v tng bilirubin mu cng ph
bin. Quinupristin / dalfopristin c ch cytochrome P-450 v do c th nh hng n
nng ca cc thuc khc.
Quinupristin / dalfopristin c hot tnh chng t cu, lin cu, v mt s vi khun
rut khng thuc cao. Tuy nhin km vi mt s tc dng ph.
Ghi nh
Quinupristin/dalfopristin c tc dng tr Enterococcus faecium nhng khng c tc
dng tr Enterococcus faecalis. E. faecalis c bm tng khng sinh ra khi vi khun mt cch
tch cc.
Cu hi
24. Nhm Streptogramin gm cc khng sinh/. lm vic hp ng hip lc vi
nhau.
25. Quinupristin/dalfopristin c tc dng tt tr vi khun.hiu kh.
26. mnh ca quinupristin/dalfopristin l trn vi khun staphylococci khng,
Streptococcus pneumoniae khng, and mt s enterococci khng.
c thm
Allington DR, Rivey MP. Quinupristin/dalfopristin: a therapeutic review. Clin Ther.
2001;23:2444. Bouanchaud DH. In-vitro and in-vivo antibacterial activity of
quinupristin/dalfopristin. J Antimicrob Chemother. 1997;39(suppl A):1521. Cocito C, Di
Giambattista M, Nyssen E, et al. Inhibition of protein synthesis by streptogramins and
related antibiotics. J Antimicrob Chemother. 1997;39(suppl A):713.
Linezolid
Linezolid l thuc gn y c ph duyt thuc nh khng sinh oxazolidinone.
Khng ging nh nhiu loi thuc tho lun cho n thi im ny, c phn lp t vi
khun hoc nm, nhm oxazolidinone l nhng hp cht tng hp. Cu trc linezolid gm
c mt li oxazolidinone c bin i ti mt s v tr (Hnh. 6-10). Bng cch lin kt
cc tiu n v 50S ca ribosom vi khun, n ngn chn qu trnh lin kt ca cc tiu n v
ny vi tiu n v 30S, nhm lm mt s lp rp ribosome. N cng c ch tng hp
protein bng cch ngn chn s hnh thnh ca cc peptit u tin ca peptide mi. Mc d
linezolid l mt thuc mi khng c tm thy trong t nhin v cu trc ca n c nht
trong s cc tc nhn khng khun, khng c pht hin. l hu qu ca t bin
gen m ha amino acid mt phn ca ribosome. iu th v l, mt s trc khun gram m
hiu kh nh Escherichia coli l khng t nhin vi linezolid v chng sn xut bm tng
thuc hot ng chng li hp cht ny.
Linezolid c tc dng tuyt vi chng li hu ht cc vi khun Gram dng hiu kh,
bao gm c t cu khng methicillin, S. pneumonia khng penicillin, v enterococci khng
vancomycin (Bng 6-14). N cng c tc dng in vitro chng li mt s vi khun gram m
hiu kh, vi khun k kh v vi khun khng in hnh, nhng hin khng c s dng
iu tr cc nhim khun do cc vi sinh vt ny. Linezolid c sn dng ung v tim tnh
mch v t nng cao trong huyt thanh tng t khi dng c 2 dng ny.
c tnh
Linezolid ni chung c dung np tt. Ging nh hu ht cc loi thuc khng sinh,
n gy ra cc triu chng trn tiu ha nh bun nn, nn ma v tiu chy. Gim tiu cu,
thiu mu, gim bch cu xy ra kh thng xuyn nhng c th hi phc. Linezolid khng
nn dng vi cc thuc c ch monoamine oxidase (MAO). S dng thn trng vi cc
thuc c ch th th serotonin v s kt hp ny c th dn n hi chng serotonin, bao
gm st, kch ng, thay i trng thi tm thn, v run.
Linezolid l mt s b sung quan trng vo danh sch khng sinh ca chng ta.
Thuc ny c tc dng tuyt vi chng li cc vi khun Gram dng hiu kh, trong c
nhiu chng khng vi cc khng sinh khc.
Hnh 6-10. Cu trc cu linezolid
69
Cu hi
27. Linezolid c tc dng tt trn vi khun gram dng khng nh staphylococci
khng.v enterococci khng.
28. Thuc ny gn vivi khun v c ch tng hp protein.
29. Mt li th ca linezolid l t nng trong huyt thanh tng t nhau d dng
ng.hay ng..
c thm
Hamel JC, Stapert D, Moerman JK, et al. Linezolid, critical characteristics. Infection.
2000;28:6064. Moellering RC. Linezolid: the rst oxazolidinone antimicrobial. Ann Intern
Med. 2003;138:135142. Swaney SM, Aoki H, Ganoza MC, et al. The oxazolidinone
linezolid inhibits initiation of protein synthesis in bacteria. Antimicrob Agents Chemother.
1998;42:32513255.
Nitrofurantoin
Nitrofurantoin l mt loi thuc c, ln u a ra th trng vo nm 1953. N
thuc nhm cc hp cht c gi l nitrofuran (Hnh. 6-11). Bi v nitrofurantoin ch t
nng thp trong mu nhng c tp trung trong nc tiu, n c s dng hu nh
iu tr vim bng quang cp tnh. N khng c khuyn co cho vim b thn v cc bnh
nhim khun ny thng lin quan gy nhim khun huyt. C ch tc dng ca
nitrofurantoin vn km c trng nhng n c th lin kt ribosome v c ch dch m. iu
ny c th nh hng xu n qu trnh chuyn ha carbohydrate trong vi khun.
Nitrofurantoin c hot tnh chng li nhiu loi sinh vt thng gy ra nhim khun ng
tit niu, bao gm c vi khun gram m hiu kh (tr Proteus spp. v P. aeruginosa) v vi
khun Gram dng hiu kh, chng hn nh vi khun rut v Staphylococcus saprophyticus
(Bng 6-15). khng vi thuc ny l him gp. Nitrofurantoin ch c sn dng ung.
c tnh
S dng Nitrofurantoin lin quan vi mt s phn ng bt li, bao gm bun nn,
nn, pht ban, phn ng qu mn phi v vim phi k, vim gan, thiu mu tan mu, v
thn kinh ngoi bin.
Nitrofurantoin l mt "ngch" khng sinh vi hot ng tuyt vi chng li nhiu
loi vi khun thng gy vim bng quang cp tnh. N khng t c mc tc dng tr
liu trong cc m c th bn ngoi ng tit niu v khng nn s dng iu tr cc loi
bnh nhim trng khc.
Cu hi
30. Nitrofurantoin c tc dng tt tr nhiu vi khunhiu kh v vi khunthng
gy vim bng quang cp.
31. Nitrofurantoin khng t nng cao trong v v vy khng nn dng tr
cc bnh nhim khun h thng hoc vim b thn.
32. D hng thp k s dng, rt t.vi nitrofurantoin xut hin.
Hnh 6-11. Cu trc ca nitrofurantoin
71
c thm
Cunha BA. Nitrofurantoin: an update. Obstet Gynecol Surv. 1989;44:399406.
Cunha BA. New uses for older antibiotics: nitrofurantoin, amikacin, colistin, polymyxin B,
doxycyline, and minocycline revisited. Med Clin North Am. 2006;90:10891107. Mandell
GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennetts Principles and Practice of
Infectious Disease. 7th ed. Philadelphia, PA: Churchill Livingstone/Elsevier; 2010:515520.
Chng 7: Khng sinh tc ng ti ADN v s sao chp

Ng Hng Qun, sinh vin DHYD Hi Phng
Trong trn chin gia cc vi khun xm lc v s p ng ca h min dich con

ngi, u th v s lng thng xuyn l yu t quyt nh. Vi khun c li th trong vn
ny do chng c kh nng phn chia nhanh; v mt ngha no , chng c th t tip
tc tip vin qua s sao chp nhanh chng. Mt s khng sinh ngn chn s tip vin ny
bng cch c ch DNA sao chp ca vi khun v theo nhn rng ln vi khun. Trong cc
iu sau y, chng ta s tho lun v cc tc nhn khng khun mt cch chi tit.
Nhm thuc Sulfa
Cc thuc Sulfa c t rt lu i v s dng li vo u th k 20. Nh th, th h
khng sinh ny s dng trc c cc nhm penicillin. Trong phn ny, chng ta s tho lun
hai thuc ca nhm thuc ny vn c s c s dng rng ri: trimethoprim-
sulfamethoxazole and dapsone (Table 7-1). Thuc th 3, sulfi soxazole, c s dng kt
hp vi erythromycin cha vim tai gia tr em. Nh ci tn ca n gi ,
trimethoprim-sulfamethoxazole thc ra l s kt hp ca 2 tc nhn khng khun:
trimethoprim v sulfamethoxazole. Trimethoprim khng thuc nhm sulfa nhng c ch tc
dng ging vi cc thuc nhm ny. Khng lu i nh nhm sulfa nhng d sao cc vt
tch v ngun gc t nm 1950 1960. Cc t ph trong s pht trin ca trimethoprim-
sulfamethoxazole, tuy nhin, ch n nm 1968 pht hin ra rng hai cht kt hp gy ra hiu
lc mnh. Trong 30 nm qua, trimethoprim-sulfamethoxazole c s dng iu tr
cc bnh nhim khun khc nhau.
Trimethoprim-sulfamethoxazole c ch s pht trin ca vi khun bng cch ngn
chn s tng hp ca tetrahydrofolate (THF), trng thi hot ng ca acid folic. THF l
mt yu t cn thit cho con ng chuyn ha to nn cc deoxynucleotid, cn thit cho
cu trc AND(Fig.7-1). Sulfamethoxazole c cu truc tng t para- aminobenzoate
(PABA) v do cnh tranh c ch enzyme dihydropteroate synthase, ci enzym ny kt
hp vi PABA vo qu trnh tng hp THF(Figs. 7-1 and 7-3). Trimethoprim, mt khc c
cu trc tng t dihydrofolate do c ch dihydrofolate reductase, enzym cn thit cho s
chuyn ca dihydrofolate thnh THF (Figs. 7-1 v 7-3). Nh vy, hai khng sinh c ch hai
bc ring bit trong qu trnh tng hp, v theo cch ngn chn cc sn phm kt hp
cn thit cho s pht trin ca vi khun trong khi gim xc sut vi khun khng thuc pht
trin. Tuy nhin, s ni ln ca cc chng khng thuc hn ch vic s dng
trimethoprim-sulfamethoxazole. Vi khun tr nn khng vi c 2 yu t bng cch sn xut
ra cc enzym ch bin i khng b c ch bi khng sinh hay s thay i tnh thm ngn
chn s tch t ca khng sinh bn trong vi khun. Mt s chng sn xut tha PABA, t
n ngng nng c kh nng cnh tranh thnh cng vi sulfamethoxazole cho
dihydropteroate synthase, dn n khng sulfamethoxazole.
Trimethoprim-sulfamethoxazole hot ng chng li mt phm vi rng cc vi khun
Gram dng v m a kh (Table 7-2). Tuy nhin, vic s dng rng ri trong mt thi gian
di, nhiu chng nhy cm nay khng. Nhiu lin cu v t cu vn nhy cm vi s
73
kt hp thuc ny. Mt s dng ca Enterobacteriaceae nh Escherichia coli, S almonella
spp., v Shigella spp., cng nhy cm, cng nh mt s chng ca Haemophilus influenzae.
Vi khun k kh v a kh c xu hng khng vi trimethoprimsulfamethoxazole. Tc nhn
ny c trong c dng ung v dng tim. Khi ung ng ung, c hai thuc hp thu tt, v
nng thuc trong huyt thanh tng ng vi ng tim tnh mch. Dapsone l loai
thuc sulfa ng th hai v s dng ph bin. Cu trc ca n lin quan n
sulfamethoxazole (Fig. 7-4) v n c cng c ch tc dng. Tuy nhin ph tc dng ca n
kh l khc bit. S dng Dapsone nh l mt yu t khng khun c gioi hn iu tr
bnh phong, do vi khun Mycobacterium leprae (Table 7-2).
Lch s
Thuc sulfa l nhng thuc khng khun u tin M. Nm 1935, sulfachroidine
c s dng cha cho b gi 10 tui b vim mng no do Haemophilus influenzae.
Cha ca bnh nhn l mt nh vvt l, nghe c rng s dng thuc sulfa c c
s dng iu tr thnh cong cc bnh nhim trng do vi khun. V th ng t hi mt s
sulfachrysoidine c th iu tr cho con gi mnh. iu ny c thc hin nhng tht bi
v c con gi cht.
- Vic s dng khng sinh u tin M- Am J Dis 1974; 128: 207-211.
c tnh
Bi v cc t bo ngi khng tng hp c acid folic, do thiu dihydropteroate
synthetase, ch ca sulfamethasone. T bo ngoi cha dihydrofolate reductase, ti ch
THF thnh dihydrofolate, nhng trimethoprim hot ng c ch enzym ca vi khun gp
50k 100k ln so vi enzym ca ngi. V vy, ngi ta hi vong rng trimethoprim-
sulfamethoxazole s t c, nhng khng phi. km theo cc tc dng ng tiu ho nhu
st, pht ban( bao gm hi chng Steve and Johnson), gim bch cu, gim tiu cu, vim
gan v tng kali mu. V nhng l do khng r rng, cc c nhn nhim HIV d dng b ng
c trimethoprim-sulfamethoxazole. Dapsone gy ra cc tc dng ph tng t, thm v ,
n cn lien quan n bnh tan huyt v methemoglobinemia. Cc thuc sulfa l cc khng
sinh lu i m vn c s dng ph bin ngy hm nay. Trimethoprim-sulfamethoxazole
c s dng iu tr cc bnh nhiim trng do vi khun a kh Gram dng v m.
Dapsone l mt la chonj cho bnh phong.
Kt lun
Mt s vi khun, nh cc t bo ngi, c kh nng chim acid folic t mi trng
v khng cn phi tng hp yu tos ny. V d, enterococci b c ch bi trimethoprim-
sulfamethoxazole mc trung bnh trong phng th nghim khng cha acid folic. Tuy
nhin, trimethoprim-sulfamethoxazole khng hiu qu trong iu tr nhim khun ng
rut bi v cc vi khun ny c th s dng acid folic trong c th con ngi.
75
Cu hi
1. Trimethoprim v sulfamethoxazole l cc khng sinh c cu truc khng lin quan v cng
c ch s tng hp ca ..
2. S kthp ca cc khng sinh c hot ng chng lai vi khun a kh .. v
3. Cc c nhn b bnh d dng b mc cc c tnh ca trimethoprim-

sulfamethoxazole
4. Cht khng khun u tin Dapsone c s dng iu tr
ADDITIONAL READINGS
Burchall JJ. Mechanism of action of trimethoprim-sulfamethoxazole. II. J Infect Dis.
1973;128
(suppl):437441.
Huovinen P. Increases in rates of resistance to trimethoprim. Clin Infect Dis. 1997;24(suppl

1):
S63S66.
Masters PA, OBryan TA, Zurlo J, et al. Trimethoprim-sulfamethoxazole revisited. Arch
Intern Med.
2003;163:402410.
Meyers WM. Leprosy. Dermatol Clin. 1992;10:7396.
77
Quinolones
Nhm quinolone, nh penicillin, u c may mn pht hin ra. Vic khm ph ra
th h khng khun ny c th bt ngun t vic quan st thy mt sn phm ph trong qu
trnh tng hp chloroquine, mt hp cht chng st rt, c tc dng km vi vi khun Gram
m. Cc s thay i tip theo ca hp cht ny dn n cc yu t vi hiu lc chng li vi
khun a kh Gram m v dng, thm ch c mt s vi khun k kh. Ph tc dng rng, kh
nng hp th cao khi dng ng ung, v nhng c tnh thp l nhng nguyn nhn nhm
quinolon tr thnh mt trong nhng khng sinh c s dng ph bin nht hin nay. Trong
s cc quinolon, ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin v gemifloxacin c
s dng nhiu nht (bng 7-3). Tt c cc quinolon thng mi u c cu trc vng i
(hnh 7-5). Trong thay i ca chnh cu trc ny, ta pht hin ra nu thm vo fuorine th s
tng cng hiu lc v th tt c cc quinolon s dng ngy nay u c tch hp thm
fluorine. V l do ny, nhng thuc ngy nay c gi l fluoroquinolon phn bit vi cc
nhm c hn nh acid nalidixic (khng c fluorine). Nhm quinolon hot ng bng cch c
ch hai enzym topoismerase, l enzym ca vi khun iu chnh vng xon ca vi khun. Cc
topimerase ny gi l DNA-gyrase v topomerase IV. Nhm quinolon n nh s phc tp
ca cu truc gia topoismerase v DNA giai on DNA t v nhng trc khi ti tht li,
kt qu hng ng cc mnh v kp b v trong nhim sc th. Nhng mnh v ny bt gi
cc thit b sao chp DNA, dn n s c ch tng hp DNA v lm cht vi khun.
S khng vi quinolon l kt qu t cc t bin t pht xut hin trong cc khu
vc c th do cc gen m ha DNA gyrase v topoisomerase IV. Khng may, mt t bin
duy nht trong cc gen l gim kh nng nhy cm vi quinolon. Vi khun vi mt t
bin nh vy sng st tt hn khi gp quinolon, v vy t bin th hai xut hin lm tng
kh nang khng quinolon. Cui cng, vi khun vi nhng t bin gen trong c DNA gyrase
v topoisomerase xut hin, v vy c kh nng khng thuc cao. Bi v mt t bin n
c c kh nng bt u qu trnh ny, khng ngc nhin khi dn n khng quinolon l yu
t chnh hn ch s dng nhng thuc ny. Mt c ch th hai ca s khng khun l s
hot ng qu mc ca bm protein trong mt s vi khun. Bi v cc bm ny
Ciprofloxacin
Ciprofloxacin l mt trong nhng fluoroquinolon lu i nht vn thng xuyn
c s dng. Nh nhiu loi fluoroquinolon, n c cha mt n xut piperazin ti chui
R1, gip tng cng hot ng chng li vi khun Gram m a kh (hnh 7-6)(ch thch: b
sung piperazine trong cu trc ca penicillin cng lm tng cng kh nng chng li vi
khun Gram m).N c phn ln hiu lc ca nhm quinolon chng li vi khun Gram m
a kh v hiu qu vi Pseudomonas aeruginosa. N kh l cn bng vi s hot ng yu
ca chng trn vi khun Gram dng. V d, ciprofloxacin khng nn c s dng iu
tr bnh nhim khun nng do Streptococcus pneumoniae. Ciprofloxacin cng c tc dn
chng li nhiu vi khun in hnh v mt s vi khun mycobacterim
Levofloxacin v ofloxacin
V mt cu trc, levofloxacin v ofloxacin gn ging nhau. Ofloxacin l mt hn hp
racemic ca cht ng phn lp th dng hot ng v khng hot ng, trong khi
levofloxacin chi gm dng cht ng phn lp th hot ng . Nh vy, hai thuc ny c
cng ph tc dng, nhng levofloxacin thng c tc dng mnh hn v th thng c s
dng hn. Levofloxacin khng mnh so vi ciprofloxacin chng li vi khun gram m a

kh nhng vn hiu qu chng li cc bnh nhim trng gy ra bi cc vi khun bao gm P.
aeruginosa. Lin quan vi ciprofloxacin, levofloxacin tng cng kh nng chng li vi
khun Gram dng a kh v c hiu qu trong iu tr cc bnh truyn nhim nng do S.
pneumoniae, bao gm nhng chng khng penicillin.
MOXIFLOXACIN AND GEMIFLOXACIN

Nhng thuc mi hn, c bit l gemifloxacin, tng cng kh nng chng vi
khun S. pneumoniae (gm c cc chng khng penicillin) v vi khun khng in hnh.
iu ny khng c li cho tc dng trn vi khun Gram m a kh, c bit l i vi P.
aeruginosa. Moxifloxacin cha mt nhm methoxy ti R2, lm tng hiu lc chng li vi
khun k kh.
C TNH
Bi v cc gyrase v topoisomerase ca ngi kh khng tng ng tng ng
vi enzym ca vi khun, quinolon ni chung l kh tt. Tc dng ph thng gp nht l cc
triu chng tiu ha 5-10% bnh nhn ung thuc nhm ny. Cc tc dng ph lin quan
n h thng thn kinh nh au u v chng mt xut hin khong 5% bnh nhn, trong khi
pht ban xut hin xp x 1-2%. Quinolon gy d dng sn ng vt, v th cn trnh s
dng tr em di 18 tui v khng s dng ph n c thai. t gn Achilles c
bo co ngoi cao tui. Quinolon c lin quan ti s ko di khong QT trong in tm
. Do , cc thucny c th nh hng ti s lon nhip tm tht nh l xon nh, c
bit khi chng c s dng cng vi cc thuc khc cng ko di khong QT. Mt s bo
co cho rng vic s dng quinolon trong qu trnh tin trin ca Clostridium difficile th c
lin quan ti s xut hin thng xuyn ca bnh tiu chy so vi cc khng sinh khc.
Quinolon l khng sinh tng i tt, hiu qu trong iu tr bnh nhim trng bi vi khun
gram m a kh, vi khun khng in hnh, v mt s vi khun Gram dng a kh v
mycobacteria. Mt s thuc cng c kh nng chng P. aeruginosa, vi khun k kh.
Kt lun
Ni chung, nhm quinolon c hot ng tt vi Streptococcus pneumoniae v c
bit hiu qu vi cc nhim trng do cc chng khng peniciliin ca chnh vi khun ny. Tuy
nhin, ciprofloxacin nn c s dng thn trng trong cc nhim trng nng do S.
pneumoniae bi v iu tr tht bi c bo co.
79
Cu hi
4. nhm fluoroquinolon c s dng hiu qu nht iu tr bnh truyn nhim do vi
khun a kh , mc d chng cng c kh nng chng li vi khun a
kh .., vi khun khng in hnh v mycobacteria.
5. Vi fluoroquinolon, hiu qu nht khi chng li vi khun
Pseudomonas
Aeruginosa
7. l khng sinh nhm quinolon hiiu qu nht chng li vi
khun k kh.
8. Nhm khng sinh quinolon tc dng ln vi khun v
.. dn n s t on trong nhim sc th ca vi khun.
9. nhm Fluoroquinolon nn c dng cho tr em mt cch thn trng v nhng lo ngi v
thng tn ti .
METRONIDAZOL
Metronidazol, 5- nitroimidazole, c pht hin vo nhng nm 1950. N tip tc l

khng sinh quan trng v thng xuyn c s dng iu tr cc bnh nhim trng do vi
khun k kh.
Metronidazol l mt phn t nh c th khuch tn th ng vo vi khun. Mt thnh
phn quan trng ca cu trc l nhm nitro m rng t 5 vng chnh. Nhm ny phi b oxy
ha (tc l nhn thm electron) metronidazol hot ng. Nh l mt phn ca b my
trao i cht, vi khun k kh c electron oxy ha kh yu , c kh nng thm nhng electron
vo nhm nitro. Vi khun k kh rt t protein bi v chng khng thch ng s c mt ca
oxy, m chnh n l cht nhn oxy rt mnh. V l do ny, ph tc dng ca metronidazol
c gii hn chng li cc vi khun k kh v vi khun a kh nng thp. Khi b
oxy ha, nhm nitro c cho l hnh thnh cc gc t do dn n ph v cc phn t DNA
v lm vi khun cht. S khng vi metronidazol kh him khi xy ra khi chng li vi
khun k kh. Khi iu ny xy ra, ngi ta cho rng do kt qu t s st gim protein vn
chuyn electron oxy ha metronidazol. S pht trin khng vi khun t a kh l ph
bin hn, nhng c ch cha r rng.
Metronidazol c hiu qu chng li hu ht cc vi khun k kh bao gm c
Bacteroides fragilis, v phn ln vi khun k kh gram dng, k c Clostridium spp. (Bng
7-5). ay l mt trong nhng s t khng sinh c hot tnh chng C. difficile v l l chn
iu tr bnh nhim trng bi vi khun ny. Vi khun t a kh (tc l tng truoqng ti u
nng oxy thp) vi khun H.Pylori cng thng nhy cm. C ng ung v tim tnh
mch ca metronidazol u c s dng. ng ung th hp thu tt v nng thuc
cng tng ng vi tim tnh mch.
C TNH
Metronidazol tng i an ton nhng c mt s c tnh nh l bun nn v kh
chu vng thng v. N cng c th gy ra mi v nh kim loi v ng cn u li.
81
Thnh thong metronidazol gy ra triu chng thn kinh nh au u, chng mt, v bnh
thn kinh ngoi bin. Metronidazol c th n n mt phn ng nh disulfuram; trnh ung
ru khi dng thuc ny. Mtronidazol cc k tt khi chng li vi khun k kh v hu ch
trong iu tr mt s vi khun t a kh, nh l H.pylori.
LCH S
Metronidazole c pht hin bi v cc hot ng ca n i vi sinh vt n bo. Tuy
nhin, mt bnh nhn ang c iu tr vi metronidazole cho Trichomonas vaginalis vim
m o, mt sinh vt n bo nhim trng, c ghi nhn nh du s ci thin trong
bnh vim li ca mnh, l gy ra bi vi khun k kh. iu ny dn n cuc iu tra ca
metronidazole hot ng chng li cc vi khun k kh.
CU HI
10. Metronidazol nhy cm cc tt vi hu ht cc vi khun
11. Metronidazol nhy cm cc tt vi cc vi khun ., nh l H.pylori.
12. Vi khun a kh khng nhy cm vi metronidazole bi v chng khng
.. nhm nitro
Chng 8. Tc nhn khng Mycobacterium

Hiu nh: DS. V Th H
Ging nh ngi dn cc khu vc b chin tranh tn ph ko di, ngi bnh mc bnh lao
c xu hng ngy cng gy yu, suy nhc v thm ch t vong do qu trnh bnh ko di.
Ly nhim tin trin chm v trc khun gy bnh pht trin kh chm. Bi v nhiu thuc
khng khun chng li qu trnh phn chia chm ca vi khun c hot tnh thp, trc khun
lao d c kh nng khng thuc khng sinh. Kt qu l iu tr cc nhim khun do
mycobacteria gy ra i hi dng phi hp nhiu loi khng sinh trong thi gian di. Cc
chng mycobacteria khc nhau gy cc bnh khc nhau, mi bnh i hi phi c phc
iu tr ring bit. Trong chng ny, chng ta tp trung vo mt s tc nhn s dng iu
tr nhim khun ph bin gy ra bi mycobacteria.
Trc khun Mycobacterium tuberculosis gy bnh lao. Phc hp Mycobacterium avium l
nhm cc vi khun mycobacteria thng gy bnh vt ch b suy gim min dch, c bit
nhng ngi b nhim HIV. Vi khun Mycobacterium leprae gy bnh phong. Mt danh
sch di mycobacteria khc thng gi l cc vi khun mycobacteria khng in hnh, cng
gy ra cc bnh khc nhau ngi. Cc thuc thng c s dng iu tr nhim khun
mycobacteria gm isoniazid, rifampin, rifabutin, pyrazinamid, ethambutol, clarithromycin
v azithromycin. Cc thuc khc i khi s dng trong iu tr nhim khun mycobacteria
gm amikacin, streptomycin, cycloserin, ethionamid, acid capreomycin p-aminosalicylic,
clofazimin, dapson v cc quinolon.
ISONIAZID
Isoniazid c hot tnh khng khun thp vi hu ht cc vi khun nhng c kh nng git
cht vi khun M. tuberculosis ni bo v ngoi bo. Isoniazid c cho l c ch enzym ch
yu tham gia tng hp acid mycolic - thnh phn quan trng ca mng t bo vi khun M.
tuberculosis. iu ny c th gii thch s c hiu ca isoniazid i vi Mycobacteria bi
v cc vi khun khc khng to ra acid mycolic. Khng thuc xy ra khi c t bin gen
m ha catalase-peroxidase cn thit chuyn i isoniazid thnh dng c hot tnh.
Tng t nh vy, cc t bin gen m ha cc enzym ch cn thit cho tng hp acid
mycolic cng gy khng thuc. Tc dng ph lin quan ti Isoniazid gm: pht ban, st, c
tnh trn gan v bnh thn kinh ngoi bin. Ung d phng pyridoxin ngn nga bnh
thn kinh.
RIFAMPIN, RIFABUTIN V RIFAPENTIN
Khng ging nh isoniazid, cc rifamycin c ph hot tnh khng khun rng. Cc thuc ny
c ch RNA polymerase ca vi khun, tho lun chi tit hn trong phn cc Rifamycin.
Mycobacteria d dng tr nn khng cc rifamycin khi chng c s dng nh n tr liu.
Khng thuc l do t bin gen m ha RNA polymerase.
83
PYRAZINAMID
Ging nh isoniazid, pyrazinamid c ch tc dng l mt enzym cn thit cho qu trnh
tng hp acid mycolic. Thuc ny ch git mycobacteria pH acid. May mn thay, M.
tuberculosis ni bo nm trong mt th thc bo c tnh acid. Do , thuc ny c hot tnh
khng li vi khun ni bo. Khng thuc do nhng t bin gen m ha pyrazinamidase -
mt loi enzym cn thit chuyn i pyrazinamid thnh dng c hot tnh. Cc tc dng
c hi bao gm c tnh vi gan v tng nng acid uric trong huyt thanh c th dn n
bnh gt.
ETHAMBUTOL
Ethambutol nhm n mt enzym tham gia vo qu trnh tng hp vch t bo trc khun
lao. Cc t bin gen m ha enzym ny dn n khng thuc. c tnh chnh ca thuc l
gy vim dy thn kinh th gic, c th dn n gim th lc v m mu (-xanh).
CLARITHROMYCIN V AZITHROMYCIN
Clarithromycin v azithromycin ngn chn qu trnh dch m to protein bng cch nhm
vo cc ribosome ca nhiu loi vi khun khc nhau, bao gm c mt s vi khun
mycobacteria. Cc tc nhn ny c tho lun chi tit hn trong phn cc Macrolid.
Mt s khng sinh c hot tnh khng khun vi cc mycobacteria. Mt s thuc trong nhm
ny nh isoniazid c s dng c hiu iu tr nhim khun mycobacteria, trong khi
cc tc nhn khc chng hn nh rifampin, biu th ph hot tnh khng khun rng vi
nhiu chng vi khun. Bi v mycobacteria c xu hng khng i vi cc thuc khng
khun v rt kh loi tr, phc iu tr thng gm nhiu thuc v phi ko di nhiu
thng. c tnh l vn v phi theo di cn thn trong thi gian di vi cc thuc c
c ch nh.
CU HI
1. Nhim khun mycobactaria thng c iu tr vi ------------------------ thuc trong -----
------------------- thi gian di.
2.,,. v ------------------------ l nhng tc nhn hng u iu tr
Mycobacterium tuberculosis.
3. Isoniazid, rifampin v pyrazinamide tt c c th gy ra ------------------------
C THM
Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for
Disease Control and Prevention/Infectious Diseases Society of America: treatment of
tuberculosis. AmJRespir Crit Care Med. 2003;167:603-662.
Di Perri G, Bonora S. Which agents should we use for the treatment of multidrug-resistant
Mycobacterium tuberculosis? J Antimicrob Chemother. 2004;54:593-602.
Petri WA Jr. Drugs used in the chemotherapy of tuberculosis, Mycobacterium avium
complex disease, and leprosy. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman and
Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: The
McGraw-Hill Companies; 2006:1203-1224.
Vilcheze C, Wang F, Arai M, et al. Transfer of a point mutation in Mycobacterium
tuberculosis inhA resolves the target of isoniazid. Nature Med. 2006;12:1027-1029
85
Chng 9: Tng hp ngn v cc khng sinh
Th.S-DS Trng L Thy Nguyn
Thc t l c nhiu loi khng sinh iu tr mt tnh trng nhim khun. v th vic nhm cc
khng sinh ny li da trn ph khng khun l iu cn thit qun l khng sinh.
1. Tc nhn gy bnh l vi khun Gr (+) hiu kh.
Nhm khng sinh c hot tnh khng khun mnh:

1. Nhm Aminopenicillin + c ch -lactamase
2. Nhm Cc Penicillin ph rng + c ch -lactamase
3. Nhm Carbapenem
4. Nhm Glycopeptid
5. Nhm Streptogramin
6. Linezolid
7. Daptomycin
Nhm khng sinh c hot tnh khng khun trung bnh

1. Nhm penicillin t nhin
2. Nhm penicillin khng staphylococcus
3. Nhm aminopenicillin
4. Nhm penicillin ph rng
5. Nhm cephalosporin
6. Nhm rifamyicin
7. Nhm aminoglycoside
8. Nhm macrolid
9. Nhm tetracyclin
10. Clindamycin
11. Nhm sulfapicin
12. Nhm quinolon
Hnh 1. Khng sinh iu tr nhim khun do vk gram(+) hiu kh
Nhng khng sinh c hot tnh khng khun mnh trn vi khun Gr(+) bao gm -lactam/ -
lactamase, carbapenem, glycopeptide, streptogramin, linezolid, and daptomycin. Trong iu tr
khng sinh theo kinh nghim, la chn nhm khng sinh ny l ti u, c hot tnh khng khun
mnh. Tuy nhin, phi nh rng, ngay c nhm khng sinh ny cng khng phi l hon ho,
mi loi s c cc nhc im ring, v d nh Carbapenem hay -lactam/ lactamase khng
c hot tnh khng khun trn Staphylococcus aureus khng Methicillin. Cng nh Vancomycin
th khng hiu qu trn enterococci khng Vancomycin, hay cc khng sinh h Streptogramin
nh Quinupristin, Dalfopristin khng c hot tnh khng khun trn Enterococcus faecalis.
c bo co v s khng ca cc vi khun Gr (+) i vi linezolid v daptomycin. V th
ng qun kim tra tnh nhy cm ca vi khun i vi khng sinh v thay i phc iu tr
theo khng sinh hp l.
C nhiu khng sinh c hot tnh khng khun trung bnh cc trn vi khun Gr (+) _ hnh 1, cc
khng sinh c ch c hot tnh trn mt s chng vi khun Gr (+), cn cc chng cn li th
khng. Do cc nhm khng sinh nh amiglycosid, nhm rifampicin ch c s dng phi
hp vi cc h khng sinh khc khi iu tr cc nhim khun do vi khun Gr (+) gy ra.
2. Tc nhn gy bnh l cc vi khun Gr (-) hiu kh.
Cc vi khun Gr (-) hiu kh l nguyn nhn c bit rc ri trong nhim trng, mt s lng ln
cc khng sinh c nghin cu pht trin nhm ch yu tc ng ln nhm vi khun ny.
Trong c cc khng sinh c hot tnh khng khun rng bao gm penicillin ph rng/ cht c ch
-lactamase; Cephalosporin th h 3,4,5; Carbapenem; Monobactam; Aminoglycosid; Colistin;
Quinolon. Nhng khng sinh ny c kh nng thm qua mng ngoi ca cc vi khun Gr (-) v
khng b bt hot bi c ch khng chung. Tuy nhin, c mt s vi khun Gr(-) s khng
vi mt hay nhiu h khng sinh thuc nhm ny, do phi kim tra tnh nhy cm ca tng
chng vi khun m bo vic tr liu l ti u. Nhm th hai l nhm khng sinh c hot tnh
khng khun trung bnh, nhm ny ch s dng iu tr vi nhim khun do mt s chng vi
khun Gr (-) gy ra-hnh 2.
Nhm khng sinh c hot tnh khng khun mnh

1 Nhm penicillin ph rng/ cht c ch -lactamase.
2 Nhm Cephalosporin th h 3,4,5.
3 Nhm Carbapenem
4 Nhm Monobactam
5 Nhm aminoglycosid
6 Nhm Colistin
7 Nhm Quinolon
Hnh 2: Khng sinh c ph khng khun trn vi khun Gr (-) hiu kh
87
3. Tc nhn gy bnh l vi khun k kh.
Cc vi khun k kh thng c khuynh hng gy ra cc nhim khun phc hp, v rt kh nui

cy trong phng th nghim. V vy nhng nhim khun ny thng c iu tr theo kinh
nghim, iu ny i hi s hiu bit ton din v ph hot ng ca tng h khng sinh. C 5
h khng sinh c hot tnh khng khun c bit rng trn nhiu vi khun k kh:
aminopenicillin/ cht c ch -lactamase; Penicillin ph rng/ cht c ch -lactamase;
Carbapenem; Metronidazol; Chloramphenicol hnh 3. Nhng khng sinh thuc nhm ny c
hiu qu trn hu ht cc chng vi khun k kh gp phi trong lm sng. Tr mt chng vi
khun quan trng l Clostridium difficile, thng lin qua n nhim khun tiu chy, ch cn
nhy cm vi Metronidazol v Vancomycin. Mc d khng ph bin nh nhm h khng sinh
u, c mt s h khng sinh khc vn hiu qu trong iu tr cc nhim khun do vi khun k
kh gy ra, v tr thnh la chn th hai trong iu tr vi khun k kh. Nhm khng sinh ny
c s dng iu tr cc nhim khun do mt hay mt nhm nh cc vi khun k kh gy ra
khi kim tra tnh nhy cm.
Nhm khng sinh c hot tnh khng khun

mnh
1. Aminopenicillin + -lactamase
2. Penicillin ph rng + -lactamase
3. Carbapenem
4. Metronidazol
5. Chloramphenicol
O2
Nhm khng sinh c hot tnh khng khun
trung bnh
1. Penicillin t nhin
2. Aminopenicillin
3. Penicillin ph rng
4. Mt s Cephalosporins th h 2
5. Vancomycin
6. Tetracycline
7. Clindamycin
8. Daptomycin
Hnh 3. Khng sinh c ph khng khun trn vi khun k kh

4. Vi khun in hnh.
Chng vi khun in kh pht hin bng cc phng php thng quy nh nhum Gram v kh
nui cy trong phng th nghim. Tuy s phn loi khng r rng, nhng n cng gip nh
hng cc khng sinh tr liu trn nhm vi khun ny. Cc chng vi khun thuc nhm ny bao
gm: Chlamydia/ Chlamydophila spp., Mycoplasma spp., Legionella pneumophila, Brucella
spp., Francisella tularensis, v Rickettsia spp.. Nhiu chng vi khun trong nhm ny c tr
trong i thc bo, hoc cc loi t bo khc. Do , cc khng sinh c th thm nhp vo cc t
bo vt ch ny s c hot tnh khng khun tt. Cc nhm khng sinh l tetracylin,
quinolone; macrolid cng co hot tnh vi mt s chng vi khun khng in hnh. Hnh 4.
Khng sinh hot tnh khng khun

mnh:
- Tetracyclin
- Quinolon
Khng sinh hot tnh khng khun trung

bnh
- Macrolid
Hnh 4. Khng sinh c ph khng khun trn vi khun khng in hnh
Phn loi hot tnh khng khun ca khng sinh trn tng chng vi khun s gip la chn khng
sinh ph hp trong iu tr. Tuy nhin phi nh l hot tnh khng khun ca tng khng sinh
trong mi nhm l khc nhau. V d nh Quinolon khng c hot tnh trn vi khun k kh
nhng moxifloxacin c hot tnh tt trn vi khun ny. Hay nh tegecyclin v tekithromycin
tng ng c ph khng khun rng hn so vi cc khng sinh khc cng nhm tetracyclin v
macrolid. Do , cc khng sinh tng kt trong chng ny ch l cc hng dn chung, mang
tnh tham kho.
89
PHN III. IU TR C HIU
Chng 10- Vi khun gram dng

Trn Th Hng Vn, sinh vin Dc H Dc HN
1. Staphylococci (T cu)
Ba loi t cu quan trng trong y t l Staphylococcus aureus, S. epidermidis v S.
saprobyticus. S. aureus (t cu vng) l tc nhn gy bnh tham cng tic vic nht. N khng
ch l vi khun thng xuyn gy ra cc nhim trng ngi m cn a n hng lot mi quan
tm v cc biu hin bnh, bao gm nhim khun huyt, vim ni tm mc, nhim trng da v m
mm, vim ty xng, vim phi v hi chng sc nhim c (Hnh 10 - 1). Chng c kh nng
l nh vic sn sinh ra mt lng ln c t gy hi ln c th vt ch hoc iu khin p ng
min dch ca n. S. aureus l mt cu khun Gram (+) pht trin thnh tng cm nh chm nho
v thng hnh thnh cc khun lc mu vng trn mi trng thch (do c tn aureus, c ngha
l vng). S. epidermidis l thnh vin quan trng nht ca mt nhm vi khun ln hn c gi l
t cu coagulase m tnh. Nhng vi khun ny c hnh thi tng t S. aureus nhng t nguy him
v t di ng hn. Chng ch yu lin quan n cc nhim trng do cc foreign objects nh ng
thng tnh mch, van tim gi v khp gi. S. saprophyticus l mt vi khun thuc nhm t cu
coagulase m tnh, gy ra nhim trng ng tit niu ti cng ng.
HNH 10 2: C ch khng khng sinh ca Staphylococcus aureus

(1)Mc d penicillin bc u c hiu qu chng li vi khun ny, tuy nhin hin nay hu ht cc
chng sinh lactamase phn hy c penicillin. V l do ny, ngi ta pht trin cc
penicillin khng t cu c kh nng chng li s phn hy ca t cu sinh lactamase. (2) Tuy
nhin, nhng chng t cu khng methicillin (MRSA) thay i protein lin kt vi penicillin
(PBP) (c gi chung l PBP2) khin cho methicillin hay cc lactam khc khng nhn din
c n. Vancomycin mt glycopeptid trnh c nhng kh khn ny do n lin kt vi nhm
alanin alanin tn cng chui bn peptid ca peptidoglycan v do ngn cn s to thnh
lin kt ngang ca peptidoglycan m khng lin kt vi cc PBP. (3) Cc chng t cu khng
Vancomycin hin c ghi nhn. Mt trong s nhng chng ny khng Vancomycin bng
cch thay i cu trc ca chui bn peptid ca tiu n v peptidoglycan mi c hnh thnh
lm cho Vancomycin khng nhn dng c chng.
Mt ci nhn khi qut v nhng c gng trong vic iu tr nhim trng do S. aureus l mt minh
chng cho kh nng ca vi khun c th chng li nhng n lc ca chng ta trong vic tiu dit
vi khun (Hnh 10 2). Trong nhng nm 1940 v 1950, nhim trng gy ra bi S. aureus c
iu tr bng penicillin, khng sinh c tc ng chng li thnh t bo dy ca loi vi khun ny.
Tuy nhin, s khng sm c hnh thnh nhng vi khun sinh lactamase enzym c
kh nng phn gii penicillin (Bc 1 trong Hnh 10 -2). May mn thay, nhng penicillin khng
t cu c bin i ngn chn s ph hy ca lactamase c mt v t hot lc khng S.
aureus tt. Nhng i din ca nhm ny bao gm nafcillin, oxacillin, and methicillin (Methicillin
hin khng cn lu hnh M) (Bng 10 1). Bi v c hot ph v hot lc hp, nhng khng
sinh ny vn l la chn trong rt nhiu nhim trng gy ra bi S. aureus. Ngoi ra, cc
cephalosporin khng li s ph hy ca lactamase sinh ra t t cu cng c pht trin.
91
Nhng cephalosporin th h I (nh cefazolin) v mt vi cephalosporin th h II (v d
cefuroxime) kh c hiu lc, trong khi cc cephalosporin th h III (nh ceftriaxone, cefotaxim)
c hiu lc km hn. Sau ny, cc cht c ch lactamase nh clavulanat, sulbactam v
tazobactam cng c pht trin. Do , s phi hp lactam/cht c ch lactamase nh
ampicillin sulbactam, piperacillin tazobactam v ticarcillin clavulanat xut hin iu tr
nhim khun gy ra bi S. aureus. Bn cnh , mt s carbapenem (imipenem, meropenem,
doripenem) khng b thy phn bi lactamase v cng rt hiu qu trong iu tr nhim khun
do vi khun ny.
Tuy nhin t cu vng S. aureus tm mi cch chng li, theo chng thay i mt trong
s cc bm PBP ca mnh. Mt trong s cc PBP c tn gi l PBP2, n khng lin kt vi bt c
hp cht lactam no c. Chng t cu c PBP2 ny c gi chung l t cu vng khng
Methicillin (MRSA), v thc s chng khng tt c cc penicillin (bao gm tt c cc
penicillin khng t cu), cc cephalosorin v carbapenem. Nhng chng ny tr thnh vn ph
bin v nguy him trong hu ht cc ca hi sc tch cc, l mt trong nhng nguyn nhn thng
xuyn ca nhim trng mc phi ti cng ng. Chng c iu tr bng Vancomycin, mt
trong s t khng sinh vn cn gi li c hot tnh ng tin cy chng li nhng chng ny.
Khng may thay, c nhng bo co v nhng chng t cu khng Vancomycin (VRSA).
Nhng chng ny c c kh nng lm thay i phn peptidoglycan hay lin kt vi
Vancomycin, do ngn cn khng sinh ny gy ra tc dng (bc 3 trong hnh 10 2). Ch c
mt vi loi khng sinh tng i mi, chng hn nh linezolid, tygecyclin, quinupristin-
dalfopristin, daptomycin, v ceftarolin l c hot lc ng tin cy chng li cc t cu ny.
Nhng khng sinh khc, nh clindamycin, cc quinolon (ciprofloxacin, levofloxacin,
moxifloxacin), trimethoprim-sulfamethoxazole, mt s tetracyclin (mynocyclin, doxycyclin) v
cc macrolid (erythromycin, azithromycin) i khi cng c tc dng trn S. aureus, nhng nhn
chung, ch s dng nhng khng sinh ny khi bit r nhy cm hoc trong trng hp khng
th s dng nhng khng sinh u tay (bng 10 1). Rifampin hoc nhng liu hip ng ca
gentamycin i khi cng c s dng cng vi lactam hoc Vancomycin trong iu tr vim
ni tm mc hoc vim ty xng do S. aureus. Rifampin c cho l to iu kin lm sch vi
khun ny trn b mt ca cc thit b gi nh van tim nhn to hoc khp gi.
Nhim trng S. epidermidis c iu tr tng t nh nhim trng S. aureus. Gn nh tt c
cc chng khng penicillin v rt nhiu chng khng li cc penicillin khng t cu. Do
vy, Vancomycin thng c la chn iu tr nhng nhim trng ny.
CU HI
1. Hai penicillin khng t cu c s dng qua ng tim tnh mch l ______ v ________
2. Chng Staphylococcus aureus khng cc penicillin khng t cu c gi l ________
3. Ngoi vic khng methicillin, chng t cu khng methicillin cng khng tt c cc
_________________
4. Cc chng t cu vng khng methicillin d b __________________
93
2. Pneumococci (Ph cu)
Ph cu l nguyn nhn thng gp ca vim phi mc phi ti cng ng, vim tai gia, vim
xoang v vim mng no (Hnh 10 3). Nhng vi khun ny, ni r ra chnh l S. pneumoniae,
khng hot ng mt cch m thm. Thay v trn trnh khi s pht hin, ph cu tn cng c th
con ngi mt cch mnh m v trc din, gy ra mt lng ng k cc tn thng m. Kt qu
l, vic nhim ph cu c lin quan n phn ng vim lan ta, lm gia tng thm tnh trng tn
thng m.
Trong nhiu nm, vic iu tr nhim trng gy ra bi S. pneumoniae l n gin: Penicillin G
hoc Ampicillin c ch nh. Tuy nhin, vic la chn iu tr tr nn phc tp. T l cc
chng ph cu sn xut PBPs ngy cng gia tng, theo chng kh m b pht hin bi cc
penicillin t nhin v cc aminopenicillin, dn n tnh trng khng thuc. C khong 40% s
lng S. pneumoniae c phn lp ti Hoa K hin ny c tnh trng khng khng sinh mc
trung bnh hoc cao. Tuy nhin, trong nhiu trng hp, tnh trng khng ny c th c khc
phc bng cch nng liu penicillin hoc ampicillin cao hn, dn n t c nng thuc cao
hn, v kt qu l, gn vo PBPs v gy dit khun.
Tnh trng ny tr nn phc tp hn khi m mt s lactam, v d nh penicillin, t c
nng trong mu v trong phi cao hn gp khong 100 ln
trong dch no ty. Nh vy, mt chng ph cu khng vi penicillin c th b git cht bi

nng cao penicillin c mt trong phi nhng vn tn ti vi s lng thp trong dch no ty.
So vi cng thi k, vic khng li cc cephalosporin vn thng c s dng iu tr

nhim ph cu cng tng ln. Nhng cephalosporin ny bao gm cefuroxim, ceftotaxim,
ceftriaxon v cefepim. Ging nh cc penicillin, cc cephalosporin t c nng trong huyt
tng v trong phi cao hn trong h thng thn kinh trung ng. Do , lp lun tng t c
p dng cho vic khng c cephalosporin v penicillin.
Vy th, lm th no iu tr cc bnh nhim trng ny? Ni chung, cc hng dn iu tr

sau y c p dng trong vic iu tr nhim ph cu vi cc penicillin (Bng 10 2). Vim
phi, vim tai gia, vim xoang v cc nhim khun gy ra bi tt c nhng nht l cc chng S.
pneumoniae khng thuc c th c iu tr vi liu cao ca penicillin. Tuy nhin, khng sinh
ny khng nn c s dng iu tr vim mng no gy ra bi cc chng ngay c ch c
khng mc trung gian. Tng t nh vy, cc cephalosporin th h III nh cefotaxim v
ceftriaxon c th c s dng iu tr hu ht cc trng hp nhim ph cu khng phn bit
nhy cm, ngoi tr vim mng no gy ra bi chng khng thuc cao.
95
Nhng kh khn trong vic iu tr cc nhim trng gy ra bi nhng ph cu khng penicillin
s tr nn phc tp bi thc t rng nhng vi khun ny cng thng khng mt vi loi khng
sinh khc. Vt liu di truyn m ha cho vic khng penicillin cng thng mang gen gy mt
nhy cm vi cc khng sinh thng c s dng iu tr nhim ph cu khc. Nhng khng
sinh ny bao gm macrolid (azithromycin), tetracyclin (doxycyclin), clindamycin v thuc sulfa
(trimethoprim v sulfamethoxazol). i vi cc nhim trng gy ra bi chng khng thuc cao, c
mt vi la chn (Bng 10 2). Mt s quinolon nht nh (moxifloxacin, gemifloxacin, v
levofloxacin nhng khng c ciprofloxacin), mt s khng sinh tng t macrolid (telithromycin)
v cephalosporin th h V (ceftarolin) vn c hot tnh chng li ph cu khng penicillin cng
nh vancomycin. Cc la chn thay th t c s dng hn bao gm linezolid, cc carbapenem
(imipenem, meropenem, doripenem), hoc cc streptogramin (quinupristin/dalfopristin).
CU HI
5. Trc s xut hin ca cc chng khng thuc, nhim trng Streptococcus pneumoniae thng
iu tr vi _____________ hoc _________________
6. Hin nay, c nhiu chng ph cu khng penicillin do chng sn xut ra _______________
khin cc khng sinh kh pht hin ra.
7. Cc khng sinh thng c s dng trong iu tr nhim trng gy ra bi cc chng ph cu
khng penicillin bao gm ___________, ______________, _____________ v __________
8. Cc chng ph cu khng penicillin cng thng khng vi cc khng sinh khc s dng
trong iu tr nhim trng gy ra bi vi khun ny, bao gm ____________, ______________,
_______________ v ____________.
3. Lin cu khun khc

S. pneumoniae ch l mt trong s rt nhiu loi lin cu quan trng trong y t. Vi khun c
phn loi nh l Streptococcus pyongenes (cn c gi l lin cu nhm A) l mt nguyn nhn
thng xuyn gy ra vim hng, nhim khun da v m mm, v hi chng sc nhim c lin
cu (Hnh 10 4). Cc chng Streptococcus agalactiae (cn c gi l lin cu nhm B) xm
chim ng sinh dc n, gy ra nhim khun huyt v vim mng no tr s sinh v tr nh
di 3 thng tui. Nhm lin cu viridans, mt nhm ln khng ng nht ca lin cu c xc
nh bi m hnh gy tan mu khi c nui cy trong mi trng thch mu, xm chim ng
tiu ha v ng sinh dc ngi, v l cn nguyn ca nhiu nhim trng nghim trng, trong
c nhim trng gy vim ni tm mc v apxe.
97
Hng iu tr thng thy trong cc nhim trng gy ra bi lin cu bao gm cc penicillin t
nhin hoc cc aminopenicillin (Bng 10 3). Nhim trng gy ra bi S. pyogenes thng c
iu tr bng penicillin hoc ampicillin. Cc la chn thay th khc nh l cephalosporin th h I
(nh cefazolin) hoc mt macrolid (nh azithromycin), mc d vic khng vi macrolid ngy
cng tr nn ph bin. Trong nhim khun nng do xm ln bi lin cu nhm A, nh l hoi t
c, clindamycin c thm vo mt ch penicillin liu cao. V mt l thuyt, clindamycin c
ch s dch m to thnh protein, ngn chn s sn xut ca mt vi c t lin cu lin quan n
c ch bnh sinh ca nhng bnh ny. Globulin min dch ng tim tnh mch (IVIG) cng
thng c p dng trong cc tnh trng ny do n c th cha khng th lin kt v trung ha
cc c t ny. S. agalactiae u cn nhy cm vi penicillin v ampicillin. Liu hip ng ca
mt aminoglycosid nh l gentamicin thng c thm vo u trong cc phc iu tr nhim
trng nng. Mc d penicillin vn l khng sinh c la chn i vi nhim trng gy ra bi
nhm lin cu viridans, tuy nhin s khng vi khng sinh ny ngy cng gia tng ph bin.
Cng ging nh S. pneumoniae, s khng l do s thay i PBPs. Vancomycin hay cc
cephalosporin (v d cefotaxim) c s dng iu tr cc chng khng thuc ny. Mt
aminoglycosid (v d gentamicin) i khi c kt hp vi cc khng sinh ny mang li tc
dng hip ng.
CU HI
9. Khng ging nh Streptococcus pneumoniae, Streptococcus pyogenes tip tc gn nh l nhy
cm vi ____________
10. Trong iu tr nhim trng xm ln nghim trng do lin cu nhm A, _____________ nn
c s dng kt hp vi penicillin.
11. Lin cu nhm viridans khc vi lin cu nhm A v B l chng thng khng vi
___________
12. Trong iu tr nhim trng gy ra bi S. agalactiae v lin cu nhm viridans, ____________
i khi c s dng cng vi penicillin bi v tc dng hip ng ca cc khng sinh ny.
4. Enterococci (cu khun rut)

Cu khun rut c th c xem nh l c dn hay thay i ca ng tiu ha. Bnh
thng, chng tr ng trong mi trng ny mt cch v hi, sinh trng v nhn ln trong mi
trng rut non giu cht dinh dng m khng gy nn bt c vn g cho c th vt ch. Tuy
nhin, nu c th tr nn d b gy hi theo mt cch no , nhng vi khun ny c th quay ra
tn cng v gy ra cc nhim trng nghim trng. Cc v tr nhim trng bao gm ng thng mch
mu hay tit niu, phu thut bng, hoc l cy ghp c quan. Bnh ng rut biu hin nh l
nhim trng ng tit niu, nhim khun huyt, vim ni tm mc, nhim trng vt thng hoc
nhim trng bn trong bng (Hnh 10 5). Loi cu khun rut hay gp gy bnh cho ngi nht
l Enterococcus faecalis v Enterococcus faecium.
Mt vn ng quan tm i vi nhng cu khun rut ny chnh l kh nng khng vi

rt nhiu khng sinh ca chng (hnh 10 6). Bn thn nhng vi khun ny khng vi cc
cephalosporin do chng thay i PBPs. Chng cng c kh nng tn dng ngun dn xut acid
folic t mi trng xung quanh, khin chng khng c trimethoprim sulfamethoxazol.
Ngay c vi cc penicillin v vancomycin l nhng khng sinh c tc dng dit khun i vi cc
vi khun cn nhy cm, cng ch c tc dng km khun i vi nhng vi khun ny.
99
HNH 10 6: C ch khng khng sinh ca Enterococci. mt vi chng, vic thay i
peptidoglycan ngn cn vic gn vi Vancomycin. PBPs ca cu khun rut khng b nhn ra bi
cc cephalosporin, v mt s chng n khng gn vi bt c mt lactam no c. Enterococci
khng cn tn hp folat bi v chng ng ha t chnh c th vt ch, kt qu l khng
trimethoprim sulfamethoxazol. Vic gim tnh thm vi aminoglycosid gy ra tnh trng
khng mc thp, trong khi vic bin i aminoglycosid v t bit ribosom lm cho
khng mc cao.
Cc khng sinh la chn u tay c s dng trong iu tr nhim cu khun rut l cc

penicillin, c bit l penicillin G, ampicillin v piperacillin (bng 10-4). Nhng carbapenem nh
imipenem, meropenem v doripenem i khi cng c hot tnh. Tht khng may thay, s khng
vi cc khng sinh ny ca cu khun rut ngy cng gia tng, thng l do chng thay i PBPs
khin cho cc lactam khng th gn vo c. i vi nhng chng ny, Vancomycin c
la chn thay th lactam. Tuy nhin, vic khng vi vancomycin cng tr nn ph bin.
Cu khun rut khng vancomycin (VRE) sn xut ra peptidoglycan m cha chui bn peptid
c thay i. Phn kt thc ca chui bn peptid c bin i t D alanin D alanin
thnh D alanin D lactat. Trong khi D- alanin D- alanin th lin kt vi Vancomycin cn D-
alanin D- lactat th khng, do dn n khng vi khng sinh ny. Nu khng cn nhy cm
vi penicillin, VRE cn phi c iu tr bng linezolid, daptomycin, tygecyclin, hoc
quinupristin/dalfopristin. Cn lu rng, cc khng sinh pha sau ch c hot lc chng li E.
faecium, khng c tc dng trn E. faecalis.
Tng tc gia cu khun rut v cc aminoglycosid kh phc tp. Cu khun rut thng
khng thm tt cc khng sinh aminoglycosid, kt qu l chng
101
khng mc thp vi cc khng sinh ny, lm cho cc khng sinh ny khng my hiu qu khi
dng n c. Tuy nhin cc aminoglycosid tng tnh thm vo cc t bo vi khun ny khi s
dng kt hp vi mt khng sinh thch hp c kh nng ph v vch t bo (v d mt penicillin
hoc vancomycin), v do c tc dng hip ng chng li cu khun rut. Tc dng hip ng
ny thay i hot tnh ca penicillin v vancomycin t km khun sang dit khun. ngha ca
thay i ny l tc dng dit khun c p dng trong nhng nhim trng cu khun rut
nghim trng nh l vim ni tm mc. Khng may thay, c mt vi yu t lm hn ch tnh hu
ch ca tc dng hip ng ca aminoglycosid. Tt c cc chng E. faecium c nhim sc th m
ha cho acetyltransferase enzym bin i tobramycin v cn tr khng sinh ny ngay c khi n
c tc dng hip ng. Nh vy, ch c gentamicin v streptomycin l c khuyn co s dng
trong iu tr nhim cu khun rut. Thm vo , s gia tng t l khng aminoglycosid mc
cao trong cu khun rut cng c quan st thy. iu ny xy ra khi m cc cu khun
rut c c vt liu di truyn m ha cho s tng hp cc enzym bin i aminoglycosid, lm
mt i tc dng hip ng. Cc t bin cng c th xy ra lm cho thay i v tr gn ln ribosom
cu khun rut ca cc aminoglycosid, ngn cn vic lin kt vi aminoglycosid. Trong c hai
trng hp, tc dng hip ng u b mt i.
CU HI
13. Nhng khng sinh la chn u tay cho nhim cu khun rut l lactam, _____________,
_______________, v _____________
14. Cu khun rut khng penicillin thng ng iu tr bng ____________
15. Khi s dng n c, nhng khng sinh tc ng ln thnh t bo nh lactam v
vancomycin ch ____________ cu khun rut. t c tc dng ____________, cn phi kt
hp vi gentamicin hoc streptomycin.
16. Nhng khng sinh sau y c s dng trong iu tr cu khun rut khng vancomycin:
______________, ____________, _____________ v ____________
5. Cc vi khun Gram (+) khc

Listeria monocytogenes
L. monocytogenes l mt trc khun Gram + ph bin rng ri trong t nhin. Chng thng c
tm thy trong t v phn ca ng vt n c. Vic nhim mt lng ln c t ca vi khun ny
c th dn n vim d dy rut nhng ngi khe mnh, trong khi nhng ngi rt tr,
ngi cao tui v ngi suy gim min dch c th tin trin thnh nhim khun ton thn dn n
vim mng no (Hnh 10 7). Ph n ang mang thai cng c th b nhim trng ton thn, dn
n sy thai.
Ampicillin l khng sinh c la chn cho nhim trng gy ra bi L. monocytegenes (Bng 10

5). Thot nhn, s la chn ny c v khng hp l bi L. monocytegenes c xem nh l mt
tc nhn gy bnh ni bo cn ampicillin vo cc t bo km. Li gii thch cho s bt hp l ny
l mc d L. monocytegenes xm nhp v tn ti trong nhiu loi t bo, mng no v dch no
ty, nhng phn ln chng nm bn ngoi t bo. Ampicillin dng n c ch c tc dng km
khun i vi L. monocytegenes. Kt hp vi gentamicin mang li tc dng hip ng dit khun,
v vy m khng sinh ny thng c kt hp cng vi ampicillin. Gentamicin thm nhp km
vo dch no ty, tuy nhin ch cn mt lng nh khng sinh ny c mt trong khoang l
gy ra tc dng hip ng dit khun. Bn thn L. monocytegenes khng mt s khng sinh
hay c s dng. V d, L. monocytegenes khng nhy cm vi cc cephalosporin bi v PBPs
103
ca vi khun ny khng gn vi cc khng sinh ny. Do cc cephalosporin thng c s dng
n c nh mt iu tr kinh nghim trong vim mng no, ngi ta cn phi nh thm
ampicillin vo phc iu tr nhng bnh nhn c nguy c nhim L. monocytegenes. Ngay c
vancomycin l mt khng sinh c tc dng tt trn cc vi khun Gram (+) cng c th khng t
c hiu qu iu tr trn mi bnh nhn b vim mng no do L. monocytegenes. Bnh nhn nu
khng th dung np c ampicillin c th c iu tr bng trimethoprim sulfamethoxazol.
Bacillus anthracis
B. anthracis l mt bo t vi khun Gram dng v l nguyn nhn gy bnh than. Bnh than biu
hin mt trong ba th: ng h hp, da v ng tiu ha (Hnh 10 8). Trong bnh than
ng h hp, bo t than c ht vo trong phi, gy nn vim hch xut huyt trung tht, trn
dch mng phi c mu v nhim khun huyt. Vic s dng bo t bnh than nh mt tc nhn
khng b sinh hc din ra vo nm 2001 ti Hoa K v dn n 11 trng hp c xc nhn
l bnh than ng h hp. Bnh than da c c trng bi mt vt lot c vy en trung tm
v c bao quanh bi cc vng ph n.
Bnh than ng tiu ha tng i him v thng xy ra sau khi n tht b nhim khun dn n
nhim trng ng rut vo c trng.
Trong lch s, penicillin c s dng iu tr bnh than, nhng sau ngi ta nhn ra
rng vi khun ny c mt gen cm ng dn n khuyn co rng khng th s dng n c
penicillin cho ch nh ny. Hin nay, ciprofloxacin hoc doxycyclin c la chn trong iu tr
bnh than (Bng 10 6). Bnh than ng h hp c th c iu tr vi mt trong hai khng
sinh trn kt hp vi cc khng sinh hng th hai, v d nh rifampin, vancomycin, penicillin,
ampicillin, chloramphenicol, imipenem, clindamycin hoc clarythromycin. Do mc nghim
trng tim tng ca bnh than, ngi ta cho rng li ch ca ciprofloxacin hoc doxycyclin vt
tri so vi nguy c ca chng trn tr em v ph n mang thai, do m chng c khuyn co
s dng trn hai nhm bnh nhn ny. Do mc nghim trng ca bnh than ng h hp,
nhng ngi tip xc vi bo t B. anthracis nn c iu tr d phng bng ciprofloxacin.
CU HI
17. ____________ c hot tnh chng li L. monocytegenes, nhng ____________
thng c s dng vi khng sinh ny t c tc dng hip ng dit khun.
18. L. monocytegenes khng vi ______________ - khng sinh thng c s dng iu
tr vim mng no theo kinh nghim.
19. nhng bnh nhn khng th s dng penicillin do d ng, _____________ c s dng
iu tr nhim trng L. monocytegenes.
105
20. Nhng khuyn co gn y cho rng tt c cc bnh nhn mc bnh than s c s dng mt
trong cc khng sinh sau: ___________ hoc ____________
21. Bnh nhn mc bnh than ng h hp nn c iu tr vi t nht __________ khng sinh.
Chng 11. Vi khun gram m

Dch: Phm Ngc Anh Qu H Y Dc Hu
Hiu nh: DS. V Th H
Vi khun gram m c c trng bi mt cu trc bao bc t bo m nhng lin kt cho

peptidoglycan thnh t bo ng vai tr tng cng bo v. Ging nh nhng chin binh trung
c c bao bc bi gip tr, vi khun gram m bao bc bi lp thnh bng peptidoglycan vi mt
mng ngoi giu lipopolysaccharide (LPS). Mng ngoi ny hnh thnh mt hng ro dy ngn cn
s xm nhp ca nhiu khng sinh vo trong khong gian mng v t bo cht ca vi khun. Nh
vy, chng li vi khun gram m mt cch hiu qu, khng sinh phi xuyn thu c mt lp
bo v b sung ny.
Vi khun gram m l mt trong nhng tc nhn gy nhim khun ph bin nht ngi. Nhm vi
khun ny bao gm Enterobacteriaceae, mt h vi khun ln gy ra nhiu nhim khun ng
tiu ha, tit niu v nhim trng c hi. Pseudomonas aeruginosa l mt tc nhn thng gp ca
nhim khun mc phi ti bnh vin v c cnh bo v s khng ca n vi nhiu th h
khc sinh. Neisseria spp., trc khun cong gram m Helicobacter pylori v Campylobacter jejuni,
v vi khun ng h hp Haemophilus influenzae v Bordetella pertussis cng c th l nhng
mm bnh cho ngi. Trong chng ny, chng ta s cp v phng php iu tr cho tng loi
vi sinh vt ny.
Enterobacteriaceae
H Enterobacteriaceae l mt h trc khun gram m ln, phn ln chng u c kh nng tr
ng trong ng tiu ha ca ngi. Bi v l do ny, chng thng c cp n nh l trc
khun gram m ng rut. Nhiu thnh vin trong h ny l mt phn ca khun ch bnh thng
ngi v ch gy bnh trong trng hp vt ch b tn thng. Nh vy, chng l nhng mm
bnh c hi. Nhng thnh vin khc ca Enterobacteriaceae, tuy nhin, li l nhng tc nhn
nguy hi, s phn lp nhng vi khun ny t phn, thng cho thy chng l tc nhn gy bnh.
Mt vi loi vi khun nm trong c hai nhm. Chng hn, trong khi phn ln vi khun Escherichia
coli sng v hi trong lng rut, mt s chng tip nhn vt liu di truyn ngoi lai khin chng
gy nn cc nhim khun tit niu hay tiu chy ngay c khi ch th khe mnh.
ESCHERICHIA COLI, KLEBSIELLA SPP., AND PROTEUS SPP.
E. coli, Klebsiella spp., v Proteus spp. l nhng mm bnh d ly hay gy nn cc nhim khun
mc phi ti cng ng cc c th khe mnh v cng thng xuyn dn n cc nhim khun
lin quan n chm sc y t. Vi khun t c ba chi ny gy nn cc nhim khun ng tit niu
mc phi ti cng ng, trong E. coli l tc nhn gy bnh thng gp nht (Hnh 11-1). c
th khe mnh, mt vi chng E. coli c kh nng gy vim ng tiu ha, bao gm tiu chy khi
du lch v tiu chy c lin quan ti hi chng tan huyt ure huyt. tr s sinh, n l nguyn
nhn hng u ca vim mng no. Klebsiella spp. gy vim phi mc phi ti cng ng ngi
nghin ru. Ngoi ra, c ba mm bnh cng thng gy nn cc nhim khun do chm sc sc
khe nh nhim khun ng tit niu bnh nhn t catheter, vim phi mc phi bnh vin,
nhim trng mu, nhim khun vt thng v nhim khun trong bng.
Chng ta khng th nm c cch iu tr cc nhim khun Enterobacteriaceae nu khng tm

hiu v men -lactamase. Chng hn, mt vi chng E. coli v Proteus mc phi ti cng ng vn
nhy cm vi cc aminopenicillin nh ampicillin ( Bng 11-1). Tuy nhin, nhiu chng gi y
thu nhn cc plasmid TEM-1 -lactamase (xem mc im quan trng), cho php chng
khng li ampicillin ngoi tr cc cephalosporin th h 1, nh cefazolin. Tuy nhin, tt c cc
chng Klebsiella cho thy c nhim sc th m ha cho men -lactamase, gip chng c kh nng
khng ampicillin. Hu ht cc nhim khun mc phi ti cng ng do E. coli, Proteus spp., v
Klebsiella spp u c th iu tr bi cc quinolones (ciprofloxacin, levofloxacin, moxifloxacin),
trimethoprim-sulfamethoxazole hay cc cephalosporin th h 1 (cefazolin). Mt ngoi l ng
lu l Proteus vulgaris, chng sn xut ra mt -lactamase c m ha trn nhim sc th,
gip chng khng li c ampicillin v cc cephalosporin th h 1. Cc cephalosporin th h ba
nh cefotaxime hay ceftriaxone, thng c dng iu tr vim b thn nng gy ra bi
nhng vi khun ny. Aztreonam cng c th c s dng.
Bng 11-
Cc khng sinh dng trong iu tr nhim khun Enterobacteriaceae
1
Nhm khng sinh Khng sinh

Escherichia coli, Klebsiella spp., Proteus
spp.
Aminopenicillins (ngoi tr cho Klebsiella Ampicillin
spp) v Proteus vulgaris)
Cc cephalosporins th h u Cefazolin
107
(ngoi tr cho P.vulgaris
Cc thuc sulfa Trimethoprime-sulfamethoxazole
Cc quinolone Ciprofloxacin, levofloxacin, moxifloxacin
Nu khng vi cc khng sinh trn
Cephalosporin th h ba Cefotaxime, ceftriaxone
Monobactam Aztreonam
Penicillin ph rng + cht c ch - Piperacillin + tazobactam, ticarcillin +
lactamase clavulanate
Carbapenem Imipenem, meropenem, doripenem, ertapenem
+ aminoglycoside trong nhim khun nng Gentamicin, tobramycin, amikacin
Enterobacter, Serratia, Citrobacter, Providencia, Morganella spp.
Carbapenem Imipenem, meropenem, doripenem, ertapenem
Cc quinolone Ciprofloxacin, levofloxacin, moxifloxacin
Cephalosporin th h bn Cefepime
+ aminoglycoside trong nhim khun nng Gentamicin, tobramycin, amikacin
Salmonella enterica, Shigella spp.
Quinolone Ciprofloxacin
Cephalosporin th h ba Cefotaxime, ceftriaxone
Macrolides Azithromycin
Mt vi chng cn nhy cm vi
Aminopenicillin Ampicillin
Yersinia spp.
Amioglycoside Gentamicin, streptomycin
Terracycline Doxycline
Quinolone (Yersinia enterocolitica) Ciprofloxacin
Cc thuc sulfa (Y. enterocolitica) Trimethoprim-sulfamethoxazole
Nhng nhim khun lin quan chm sc y t th rt kh iu tr bi v nhng chng E. coli,

Klebsiella spp., v Proteus spp. gy bnh ny thng l nhng chng khng a thuc.
Nhng tc nhn tim nng hu ch bao gm cc cephalosporin th h ba, bn v nm (v d,

cefotaxime, ceftriaxone, cefepime, ceftaroline); penicillins ph rng + cht c ch -lactamase
(piperacillin-tazobactam, ticarcillin-clavulanate); v carbapenems ( v d, imipenem, meropenem,
doripenem, ertapenem), nhng vic iu tr phi c c nhn ha v da trn s nhy cm ca
tng chng vi khun phn lp. E. coli, Klebsiella spp., v Proteus spp. thng nhy cm vi
aminoglycosides, nh gentamicin, tobramycin, v amikacin. Tuy nhin, nhng tc nhn ny
thng khng c s dng nh mt liu trnh n c m c phi hp vi cc tc nhn khc
trong cc nhim khun e da tnh mng (nhim trng huyt).
Nhng -lactamase c bit mnh, cn c gi l -lactamase ph rng (ESBLs Extended-

spectrum -lactamases) v cc Klebsiella pneumonia carbapenemase (KPCs), thng l mi lo
ngi c bit mt vi chng E. coli v Klebsiella c lp, cho thy nhng -lactamase ny
khng vi hu ht cc khng sinh v rt kh iu tr.
IM QUAN TRNG
H Enterobacteriaceae c bit rt gii trong vic sn xut ra cc -lactamase bo v bn thn
chng li cc khng sinh nhm -lactamase. V vy, khi tho lun chn liu php iu tr thch hp
tr h Enterobacteriaceae cn c mt kin thc cn bn v nhng loi -lactamase m VK sn sinh
ra v cc -lactam b enzyme ny ph hy. C bn loi -lactamase l TEM-1, AmpC, -lactamase
ph rng (extended-spectrum -lactamases : ESBLs) v carbapenemase sinh bi Klebsiella
pneumonia (Klebsiella pneumoniae carbapenemases : KPCs)
TEM-1: -lactamase ny l mt plasmid c m ha v phin m lin tc. Gy khng hon

ton vi ampicillin v amoxicillin.
AmpC: -lactamase ny thng thng c m ha trn nhim sc th v c th cm ng c.
Khi c cm ng, AmpC -lactamase gy khng vi penicillin, ampicillin/amoxicillin, v cc
cephalosporin th h 1. Cc chng VK t bin phin m lin tc mt lng ln enzyme ny u
khng vi tt c khng sinh nhm -lactam (bao gm kt hp -lactama/cht c ch -
lactamase nh piperacillin-tazobactam) ngoi tr cc carbapenem.
ESBL: -lactamase ca nhm ny thng l plasmid c m ha v phin m lin tc. Chng l
nhng nan c bit bi v nhng chng vi khun sn sinh ESBL c th cho thy nhy cm vi
cephalosporin th h ba, tuy nhin trn thc t chng li khng. Nhng -lactamase ny ph
hy tt c -lactam ngoi tr carbapenem v thnh thong cc kt hp -lactama/cht c ch -
lactamase. Ngoi ra, bi v cc plasmid mang gen ESBL cng thng m ha cch thc khng
nhiu loi khng sinh khc na, nn cc chng VK sinh ESBL cng thng khng c nhiu
khng sinh khng phi -lactam.
KPC: KPCs l mt lp tng i mi ca -lactamase c tm thy ngy cng nhiu
K.pneumoniae phn lp. Nhng -lactamase ny ph hy tt c -lactam, bao gm c cc
carbapenem. Cc plasmid mang gen m ha KPCs cng m ha s khng vi cc khng sinh
khc, khin cho vic iu tr rt kh khn. Cc aminoglycoside, colistin, v tigecycline c s
dng vi mt vi thnh cng tr cc VK khng ny. Mi quan ngi y l plasmid m ha
KPCs s nhanh chng lan truyn n cc chng vi khun khc; nhng trng hp ca vic lan ta
ny c ghi nhn.
ENTEROBACTER, SERRATIA, CITROBACTER, PROVIDENCIA, AND

MORGANELLA SPP.
Hu ht nhng vi khun ny u c th c ng ti ng tiu ha ca ngi m khng gy bnh,
nhng chng c th gy vim phi, nhim ng tit niu, nhim khun bn trong bng, nhim
khun vt thng, v nhim khun huyt nhng bnh nhn ni tr ti bnh vin. (Hnh, 11-1)
Mi loi vi khun ny u mang gen -lactamase AmpC-type cm ng c c m ha trn
nhim sc th, iu ny gip n c kh nng khng penicillin, ampicillin/amoxicillin, v
cephalosporin th h 1. Phc tp hn na, nhng chng t bin m c kh nng phin m lin tc
mt mc ln enzyme ny li c th c sng st mt cch chn lc trong qu trnh iu tr vi
vi khng sinh -lactam. Nhng chng t bin ny khng vi tt c -lactam ngoi tr
carbapenems (imipenem, meropenem, doripenem, ertapenem). Mt vi chuyn gia thy rng
cefepime cng c tc ng chng li nhng chng VK ny. Mt hu qu ca vic chn lc sng
st cc chng ny l khi mt chng vi khun ban u cho thy nhy cm vi mt s -lactam c
th tr nn khng thuc trong qu trnh iu tr, dn n iu tr tht bi. Mc d nhiu khun
gram m m ha AmpC -lactamase, hin tng chn lc sng st nhng chng t bin phin m
lin tc ny l vn nguy hi c bit nhim khun Enterobacter, Serratia, Citrobacter,
Providencia, and Morganella spp. khi c iu tr vi cephalosporin th h ba (xem Ghi nh).
109
Cc chng Enterobacter, Serratia, Citrobacter, Providencia, v Morganella spp. cng thng
xuyn du nhp nhng plasmids khng nhng khng sinh khc, v vic iu tr phi ph hp vi
s nhy cm ca ring tng chng. Cc quinolone (ciprofloxacin, levofloxacin, moxifloxacin) v
trimethoprim-sulfametheoxazole thng cng hiu qu. Nh vi E. coli, Klebsiella spp., v
Proteus spp., cc aminoglycosides (gentamicin, tobramycin, amikacin) cng c dng phi
hp vi thuc khc trong cc nhim khun e da tnh mng (nhim trng huyt).
SALMONELLA ENTERICA, SHIGELLA SPP., AND YERSINA ENTEROCOLITICA

Hu ht dch bnh l do Salmonella enterica, Shigella spp., v Yersinia enterocolitica ngoi ra cn
bao gm vim ng tiu ha nhng c th khe mnh (Hnh. 11-1). Ngoi ra, vi chng S.
enterica gy st thng hn, mt nhim khun nghim trng c trng bi nhim khun huyt ko
di.
Tiu chy cp do nhim khun gy ra bi S. enterica v Y. enterocolitica ngi c h min dch

bnh thng thng thng khng yu cu iu tr khng sinh. Tuy nhin, iu tr c khuyn co
khi nhim khun lan ra n ng rut, nhim khun nng, hay bnh nhn suy gim min dch.
Khi khng sinh c ch nh, nhim khun Salmonella v Shigella nn c iu tr vi
quinolones ( nh, ciprofloxacin), cephlosporin th h ba (nh, cefotaxime, ceftriaxone), hay
azitheromycin. Mt vi chng vn nhy cm vi aminopenicillins (ampicillin) hay
trimmethoprim-sulfamethoxazole. Y. enterocolitica thng nhy cm vi aminoglycosides
(gentamicin, streptomycin), tetracyclines (doxycycline), quinolones (ciprofloxacin) v
trimethoprim-sulfamethoxazole.
YERSINIA PESTIS
Yersinia pestis l nguyn nhn ca dch hch, mt trong nhng thm ha au thng ca lch s
loi ngi. Loi vi khun ny gy ra mt vi i dch, mt trong c bit n nh l Ci Cht
en, nguyn nhn dn n ci cht ca mt phn t n mt phn ba dn s Chu u vo th k
14. Mc d mt vi trng hp bnh dch hch vn cn c ghi nhn, nhng mi quan ngi hin
nay v mm bnh ny l v tim nng s dng n nh mt tc nhn cho cuc khng b v sinh
hc. Phng php iu tr c la chn l streptomycin hay gentamicin (bng 11-1).
Doxycycline cng hiu qu.
Cu hi
1. Cc thnh vin ca Enterobacteriaceae gy cc nhim khun mc phi _________v nhim

khun lin quan _____________.
2. Nhim ng tiu mc phi ti cng ng v tiu chy gy bi Escherichia coli c th iu tr
thnh cng bi ___________hoc ___________.
3. Extended-spectrum -lactamases thng c sn xut bi ___________hoc
___________
4. Extended-spectrum -lactamases gy khng vi tt c lactam tr ___________ v thnh
thong ___________
5. Khi sn xut mt lng ln, AmpC -lactamases gy khng vi tt c lactam tr
___________ .
6. Trong cc nhim khun nghim trng nh nhim trng huyt, ___________thng c s
dng phi hp vi mt khng sinh chun tr Enterobacteriaceae.
7. Chng Salmonella enterica and Shigella spp. gy___________ . Nhng chng ny nhy cm
vi ___________, ___________, v___________ .
C THM
Livermore DM. Beta-lactamases in laboratory and clinical resistance. Clin Microbiol Rev.
1995;8:557584. Nataro JP, Kaper JB. Diarrheagenic Escherichia coli. Clin Microbiol Rev.
1998;11:142201.
OHara CM, Brenner FW, Miller JM. Classi cation, identi cation, and clinical signi cance of
Proteus, Providencia, and Morganella. Clin Microbiol Rev. 2000;13:534546.
Pitout JD, Sanders CC, Sanders WE Jr. Antimicrobial resistance with focus on beta-lactam
resistance in gram-negative bacilli. Am J Med. 1997;103:5159.
Podschun R, Ullmann U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy,
typing methods, and pathogenicity factors. Clin Microbiol Rev. 1998;11:589603.
Sanders WE Jr, Sanders CC. Enterobacter spp. pathogens poised to ourish at the turn of the
century. Clin Microbiol Rev. 1997;10:220241.
Yu VL. Serratia marcescens: historical perspective and clinical review. N Engl J Med. 1979;300:
887893.
Pseudomonas
Chi Pseudomonas bao gm nhiu loi trc khun gram m c tm thy mi trng, mt vi
trong s thng gy ra nhng nhim khun nghim trng nhng c th b suy yu. P.
aeruginosa l mt trong nhng mm bnh c hi ph bin nht trn lm sng hin nay. Vi khun
ny l tc nhn thng thy nhim khun mc phi ti bnh vin, c bit l vim phi, nhim
khun ng tit niu v nhim khun vt thng ( Hnh 11-2). Ngoi ra, ng th ca hu ht
nhng c th vi chng x nang (cystic fibrosis) cng b nhim khun trng din vi P.
aeruginosa thi im h trng thnh.
iu tr nhim khun P. aeruginosa thng phc tp bi chng c nhiu c ch khng thuc

(Hnh 11-3). Vi khun ny c mt mng ngoi khng cho cc cht thm qua m c nhng knh
porin chn lc cao, sn sinh ra nhiu knh bm thuc y ngc ra khi vi khun, v cng c mt
nhim sc th mang gien lactamase cm ng c. V nhng l do ny, aminopenicillins,
macrolides, v hu ht cephalosporins u khng c hiu lc vi vi khun ny. Tuy nhin, vn c
mt vi phng n iu tr ( bng 11-2). Penicillin ph rng piperacillin xuyn qua knh porin
mng ngoi nhng t l thp. V th, khng sinh ny phi c dng liu cao c tc dng dit
khun. Mt s cepholosporin th h ba (e.g, ceftazidime), cephalosporin th h bn (e.g,
cefepime), monobactam (aztreonam), carbapenem (e.g., imipenem, meropenem, doripenem),
quinolones (e.g., ciprofloxacin, levofloxacin), v aminoglycosides (e.g., gentamicin,
tobramycin, v amikacin) u hiu lc vi P. aeruginosa. Tuy nhin, khng phi tt c cc thuc
trong mt nhm u tng ng v hiu lc chng pseudomonas. V d, piperacillin th hin
qu hn ticarcillin, ciprofloxacin hiu qu hn cc quinolone khc, v tobramycin hiu qu hn
111
gentamicin. Trong s cc carbapenem, ertapenem khng nn dng iu tr nhim khun P.
aeruginosa. Colistin c s dng ngy cng nhiu iu tr nhim khun gy ra bi nhng c
th vi khun khng cc khng sinh khc.
Hnh 13. C ch t nhin v c c ca Pseudomonas aeruginosa. Cc c ch khng t

nhin c tt c cc chng P. aeruginosa. Nhng t bin v s thu np vt liu di truyn ngoi
li cho php mt vi chng c kh nng khng c c thm mt s khng sinh na thng qua
s tng cng cc c ch khng sn c v s sn sinh ra phng thc khng mi. K hiu
phng x biu hin s thu np ca nhng t bin lm thay i qu trnh trnh din protein.
Khng may rng, P. aeruginosa cng c bit gii vi vic tip nhn khng vi hu ht khng
sinh, v vy chng khng nhy cm chc chn vi bt c thuc khnh sinh no. S khng c
c thng qua nhiu c ch ( hnh 11-3). Cc t bin c th lm tng ln qu trnh sn xut
lactamase trn nhim sc th, dn n khng vi tt c lactam ngoi tr carbapenem v
cefepime. Tng t th, nhng t bin cng c th sn xut ra nhiu cc knh porin tng thuc ra
khi VK, dn n khng penicillin, cephalosporin, aminoglycoside v quinolone. Nhng t bin
trn gen m ha mt trong cc porin mng ngoi, cng c th ngn chn s xm nhp ca cc
carbapenems, v s sn xut ra cc topoisomerase b t bin cng lm vi khun mt nhy cm vi
cc quinolone. S khng aminoglycoside cng c th xy ra cng vi s thu np ca gen m
ha cho qu trnh sn xut cc yu t acetyl ha hay adenyl ha aminoglycoside, ngn cn chng
gn ln robosome.
Nh mt h qu ca s khng sn c v c c, cc chng P. aeruginosa thng khng nhy

cm vi mt hay nhiu khng sinh. V d, nhng kho st gn y cho thy rng c n 15 25 %
chng khng vi piperacillin, 20 30% khng ceftazidime, 40 45% khng aztreonam.
V vy, khng c phc khng sinh thng nht iu tr P. aeruginosa hiu qu, v liu trnh
phi c da trn cc ti liu v s nhy cm ca tng chng ring bit.
Bng 11-
Cc khng sinh dng trong iu tr nhim khun TKMX
2

Penicillin ph rng Piperacillin
Cephalosporin th h ba Ceftazidime
Cephalosporin th h bn Cefepime
Carbapenem Imipenem, meropenem, doripenem
Monobactam Aztreonam
Quinolone Ciprofloxacin, levofloxacin
Aminoglycoside Gentamicin, tobramcin, amikacin
Colistin
Phi hp khng sinh trong nhim khun
nng
-lactam nhy cm pseudomonas + Ceftazidime + tobramycin
aminoglycoside
Penicillin ph rng + Quinolone nhy cm Piperacillin + ciprofloxacin
pseudomonas
Thm ch cn ng quan ngi hn l s khng thuc ngay trong qu trnh iu tr thch hp ca

nhim khun P. aeruginosa, khin cho qu trnh iu tr tht bi. trnh hin tng ny, nhim
khun P. aeruginosa nng phi thng c iu tr vi hai khng sinh ng thi. Mt vi phi
hp c tc dng hip ng dit khun. Ni cch khc, s dng nhng khng sinh cng nhau c th
cho hiu qu r rt hn so vi n tr liu. Nhng phi hp ny bao gm mt -lactam nhy cm
pseudomonas vi mt aminoglycoside v cng c th mt -lactam nhy cm pseudomonas cng
vi mt quinolone nhy cm pseudomonas.
IM QUAN TRNG
Tazobactam khng c hiu lc chng li cc -lactamase ph bin ca Pseudomonas
aeruginosa. Kt qu l cc chng P. aeruginosa khng vi piperacillin thng cng
khng vi piperacillin-tazobactam
Cu hi
8. Cc cephalosporins thng c dng sau c tc dng tr trc khun m xanh: _________,
_________.
9. _________th c hiu lc vi Pseudomonas aeruginosa hn ticarcillin
10. Mt s him khun P. aeruginosa nng thng c iu tr ng thi vi cc khng
sinh_________.
11. Mt vi phi hp khng sinh cho tc dng hip ng dit khun P. aeruginosa. Cc kt hp
ny bao gm: _________+_________ v _________ + _________
C THM
Bonomo RA, Szabo D. Mechanisms of multidrug resistance in Acinetobacter species and
Pseudomonas aeruginosa. Clin Infect Dis. 2006;43(suppl 2):S49S56. Cunha BA. Pseudomonas
aeruginosa: resistance and therapy. Semin Respir Infect. 2002;17:231239. Hauser AR, Sriram P.
113
Severe Pseudomonas aeruginosa infections: tackling the conundrum of drug resistance. Postgrad
Med. 2005;117:4148. Lambert PA. Mechanisms of antibiotic resistance in Pseudomonas
aeruginosa. J R Soc Med. 2002; 95(suppl 41):2226.
Nesseria
Chi Neisseria bao gm hai loi hay gp v quan trng vi Y khoa: Neisseria meningitidis v
Neisseria gonorrhoeae. N. meningitidis l tc nhn rt ang s gy vim mng no v nhim
khun huyt ( Hnh 11-4). Nhim trng c th din ra vi tc c rt nhanh v dn n t vong
ngay nhng c th cn tr v khe mnh. N. gonorrheae l tc nhn gy bnh lu, bnh ly
truyn qua ng tnh dc. Nhng nhim trng do vi khun ny thng gy cc bnh khu tr vi
triu chng nh vim c t cung, vim niu o, vim xng chu. Tuy nhin, vi khun ny cng
c th ly lan vo mu, i n cc khp v da, gy ra bnh lu lan ta.
Cc chng ca N. meningitidis thng thng u nhy cm vi penicillin, v penicillin vn l mt

la chn iu tr loi vi khun ny ( Bng 11-3). Tuy nhin vn khng vi penicillin cng
c bo co, v th s nhy cm ca mt vi chng ring l nn c kim tra. Cephalosporin
th h ba, nh ceftriaxone v cefotaxime, t nng cao dch no ty cho hiu qu rt ton
din vi N. meningitidis. Chloramphenicol cng l mt phng n thay th cho nhng bnh nhn
khng dung np cc khng sinh -lactam. V vim mng no v nhim khun mu gy ra bi vi
khun ny c th dn n t vong rt nhanh, nn cc phng n d phng c hng dn cho
ngi nh bnh nhn ngn nga ly bnh. Ciprofloxacin, rifampin, v ceftriaxone c s
dng vi mc ch ny.
Trc y, nhim khun N. gonorrhoeae cng thng xuyn c iu tr vi penicllin. Tuy

nhin, cng vi s tng ln ca chng vi khun vi c tnh du nhp gen khng lm cho
vic iu tr tr nn khng cn hiu qu trong hu ht cc ca vim phi. Nhng c tnh ny bao
gm nhng plasmid m ha cho men -lactamase, nhng t bin lm tng knh bm thuc ra v
gim s xm nhp thng qua cc porin, s thay i cc protein gn penicillin (penicillin-binding
proteins - PBPs). May thay, nhng c ch ny khng dn n s khng cephalosporin th h ba.
V vy, nhng khuyn co hin hnh trong iu tr bnh lu khng bin chng ngi ln u
khuyn s dng ceftriaxone v cefixime (Bng 11-4). Lu rng bnh lu thng nng n hn
khi ng nhim Chlamydia trachomatis, nn trong thc t iu tr Chlamydia cng c khuyn
co cho bt k bnh nhn vi chn on nhim N. gonorrhoeae.
Bng 11- Cc khng sinh dng trong iu tr nhim khun

3 Neisseria meningitidis

Penicillin t nhin Penicillin G
Cephalosporin th h ba Ceftriaxone, cefotaxime
D phng sau khi tip xc
Rifamycin Rifampin

4 Neisseria gonorrhoeae

Cephalosporin th h ba Ceftriaxone, cefixime
Cu hi
12. La chn iu tr nhim khun Neisseria meningtidis l ______.
13. La chn iu tr nhim khun Neisseria gonorrhoeae khng bin chng ngi ln l
______ hay ______.
14. Bi v thng xuyn ng nhim khun, cc khng sinh dng tr ______ nn c ch nh
cho bt k ai ang iu tr bnh lu.
C THM
Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines,
2006. MMWR Recomm Rep. 2006;55:194.
Deguchi T, Saito I, Tanaka M, et al. Fluoroquinolone treatment failure in gonorrhea. Emergence of
a Neisseria gonorrhoeae strain with enhanced resistance to uoroquinolones. Sex Transm Dis.
1997;24:247250.
Lyss SB, Kamb ML, Peterman TA, et al. Chlamydia trachomatis among patients infected with and
treated for Neisseria gonorrhoeae in sexually transmitted disease clinics in the United States. Ann
Intern Med. 2003;139:178185.
Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial
meningitis. Clin Infect Dis. 2004;39:12671284.
115
Phy khun Gram m
C. jejuni, H. pylori, v Vibrio cholerae u c nhng im chung v hnh thi, chng u l nhng
trc khun gram m hnh cong. Ngoi ra, nhng trc khun ny u xm nhim ng tiu ha
ngi. Tuy nhin, mi loi li khc nhau biu hin bnh v cc phc iu tr chng.
CAMPYLOBACTER JEJUNI
C. jejuni l mt trong nhng nguyn nhn ph bin gy vim rut cp trn th gii. Vi khun ny
cu ng nhiu loi ng vt hoang d v thun ha; con ngi b xm nhp khi n thc n hay
nc ung nhim bn. Biu hin lm sng bao gm tiu chy, st, v au bng (Hnh 11-5).
iu tr khng sinh c ch nh ch mt bt phn nh s bnh nhn b nhim C. jejuni. S ny

bao gm cc bnh nhn biu hin st sao, tiu chy ra mu hay lin tc, cc triu chng ko di,
hay nhng bnh nhn suy gim min dch. Macrolide c u tin hn trong iu tr
(erythromycin, azithromycin, clarithromycin) hoc quinilone (ciprofloxacin), d cho t l
khng vi ciprofloxacin ang gia tng. Cc phng n thay th bao gm tetracycline (tetracylin,
doxycyline), aminoglcoside (gentamicin, tobramycin, amikacin), amoxicillin + acid
clavunanic, hay chloramphenicol (Bng 11-5).

5 Campylobacter Jejuni

La chn iu tr
Macrolide Erythromycin, azithromycin, clarithromycin

La chn thay th
Tetracycline Tetracycline, doxycycline
Aminoglycoside Gentamicin, tobramycin, amikacin
Aminopenicillin + Chn -lactamase Amoxicillin + acid clavunanic
Chloramphenicol
HELICOBACTER PYLORI
Vic khm ph ra vai tr ca H. pylori trong bnh vim lot d dy l mt trong nhng bc ngoc
to ln trong lch s Y hc khi m trc y bnh lot d dy c xem nh l mt bnh t pht.
H. pylori tr ng d dy ngi, ni m n gy ra cc phn ng vim dn n lot d dy (Hnh
11-6). Nu khng iu tr khng sinh, bnh c xu hng ko di trong nhiu nm, i khi l c
i.
Trn in vitro, H. pylori nhy cm vi mt vi khng sinh. S ny bao gm amoxicillin,

clarithromycin, metronidazole, v tetracycline (Bng 11-6). Ngoi ra, bismuth subsalycilate,
c bit rng ri M vi tn Pepto-Bismol, t ra hiu qua vi loi vi khun ny. Thnh phn
bismuth trong ch phm ny lm ri lon thnh t bo H. pylori. Mc d nhy cm trong th
nghim in vitro, H. pylori rt kh b dit hon ton khi iu tr khng sinh. C mt vi yu t khin
n kh dit nh vy. Mt c tnh rt c bit ca vi khun ny khin bnh tr nn mn tnh l n
rt d khng khng sinh. S s dng cng mt khng sinh nhiu ln khin chng H. pylori tr
ng trng din trong d dy quen dn, v mi khi chng tip xc li khng sinh s lm tng
nguy c khng. Ngoi ra, mi trng acid d dy hn ch hiu qu ca mt s khng sinh,
iu cho php H. pylori sng st lu hn trong qu trnh iu tr v khin chng tr nn
khng khng sinh. V vy, khng c g ngc nhin khi n 20-40% chng c lp khng vi
metridazole v 10% khng clarithromycin. khng metronidazole l kt qu t t bin
trong gen nitroreductase, gen m ha cho mt protein c kh nng bt hot metronidazole. Nhng
t bin mt trong cc gen m ha mt phn tiu th robosome 50S ngn cn clrithromycin gn
vo robosme. V nhiu nguyn do, t l dit khun c th bnh c iu tr vi mt khng sinh
kh thp.
i ph vi kh nng khng ca H. pylori, cc phc phi hp c s dng iu tr

loi vi khun ny ( Bng 11-6). Mi mt phc bao gm t nht hai khng sinh kt hp vi mt
khng tit acid. Thnh phn khng tit trong phc lm tng nng pH dch v, gip ti u hiu
qu ca khng sinh v cng hn ch tin trin tn thng m do tip xc vi acid.

6 Helicobacter pylori

Aminopenicillin Amoxicillin
Macrolide Clarithromycin
Metronidazole
Tetracycline Tetracycline
Bismuth subsalicylate
Phc khuyn co
Amoxicillin + clarithromycin + proton pump
inhibitor
117
Metronidazole + clarithromycin + proton pump
inhibitor
Bismuth subsalicylate + metronidazole +
tetracycline + proton pump inhibitor
VIBRIO CHOLERAE
V. cholera hin ang l mi nguy hi ton cu gy nn cc i dch t. Bnh nhn b bnh t

thng tiu chy lin tc v c th dn n t vong trong vi gi do mt nc qu nhiu (Hnh 11-
7). Khng sinh ng vai tr quan trng trong vic gim s ln i ngoi v thi gian tiu chy
nhng bnh nhn ny. Trc y, tetracycline v doxycycline l nhng la chn iu tr bnh t,
tuy nhin khng thuc ngy cng ph bin v xy ra khi cc chng tip nhn cc plasmid trnh
din ng thi cc yu t quyt nh khng a khng sinh. Nhng khng sinh hiu lc khc bao
hm quinolon (ciprofloxacin), macrolide (erythomycin, azithromycin), hay trimethoprim-

sulfamethoxazole (Bng 11-7), mc d trimethoprim-sulfamethoxazole ang dn tr nn b
khng ph bin.

7 Vibrio cholerae

Tc nhn c hiu lc
Macrolide Erythromycin, azithromycin

Sulfa Trimethoprim-sulfamethoxazole
IM QUAN TRNG
Cng vi bnh lot d dy, nhim khun Helicobacter pylori cng c cho l c lin quan
n mt dng ung th d dy, c gi l ung th m lympho lin quan n mng nhy
(mucosa-associated lymphoid tissue (MALT) lymphoma ). ng ch l vic tiu dit H.
pylori c lin quan n s thuyn gim lu di ca nhng ung th ny. iu ny l mt v d
tiu biu cho s thnh cng ca vic s dng khng sinh iu tr ung th.
Cu hi
15. Liu php khng sinh iu tr nhim khun Campylobacter jejuni nn__________c ch
nh cho cc trng hp bnh tiu chy khng bin chng bnh nhn bnh thng.
16. Khng sinh u tay trong iu tr nhim khun C. jejuni bao gm__________v__________.
17. Helocobacter pylori rt d khng khng sinh, nn cc phc iu tr khuyn
co__________ khng sinh kt hp.
18. iu tr nhim khun H. pylori bao hm hai phn: mt __________ v mt__________.
19. Trc y, __________v__________ l nhng khng sinh c la chn tr bnh t,
nhng s khng ang dn tr nn ph bin.
20. Nhng khng sinh khng c dng iu tr bnh t bao
gm__________,__________,__________, v__________.
C THM
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141146. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of
infectious diarrhea. Clin Infect Dis. 2001;32:331351.
Howden CW, Hunt RH. Guidelines for the management of Helicobacter pylori infection. Ad Hoc
Committee on Practice Parameters of the American College of Gastroenterology. Am J
Gastroenterol. 1998;93:23302338.
Lariviere LA, Gaudreau CL, Turgeon FF. Susceptibility of clinical isolates of Campylobacter
jejuni to twenty- ve antimicrobial agents. J Antimicrob Chemother. 1986;18:681685.
Megraud F. Resistance of Helicobacter pylori to antibiotics and its impact on treatment options.
Drug Resist Update. 2001;4:178186.
Walsh JH, Peterson WL. The treatment of Helicobacter pylori infection in the management of
peptic ulcer disease. N Engl J Med. 1995;333:984991.
Yamamoto T, Nair GB, Albert MJ, et al. Survey of in vitro susceptibilities of Vibrio cholerae O1
and O139 to antimicrobial agents. Antimicrob Agents Chemother. 1995;39:241244.
119
Vi khun Gram m khc
Nhiu loi vi khun Gram m khc cng hay gy ra cc nhim trng ngi. y, chng ta s
bn lun bn trong s chng: H. influenzae, B. pertussis, Moraxella catarrhalis, v Acinetobacter
spp.
HAEMOPHILUS INFLUENZAE
H. influenzae l mt trc khun nh Gram m gy ra nhng nhim khun nh v thm ch cng c
th e da tnh mnh. Vi khun ny gy ra vim tai gia, vim xoang, vim phi mc phi ti cng
ng, vim kt mc, vim mng no, vim thng v v vim khp t hoi ( Hnh 11-8). H.
influenzae type B c bit nguy him v trong qu kh l nguyn nhn chnh ca cc nhim khun
nng n nh vim mng no. Tuy nhin, hin nay n tr nn t ph bin vi vic s dng rng ri
vaccine cha khng nguyn v type B.
Ampicillin hay amoxicillin c s dng thng xuyn tr nhim khun gy ra bi H.

influenzae trong nhiu nm. Tuy nhin hin gi, c gn 30% chng du nhp cc plasmid m ha
men -lactamase c th ph hy nhng khng sinh ny. May mn thay, nhng -lactamase ny b
phong b bi clavunate v sulbactam, nn kt hp aminopenicillin/cht c ch -lactamase (
amoxicillin + clavulanate, ampicillin + sulbactam) vn c hiu lc (Bng 11-8). Tng t,
cephalosporin th h hai v ba ( cefuroxime, ceftriaxone, cefotaxime) cng hiu qu vi -
lactamase ny. Nhng khc sinh hiu qu khc bao gm quinolone ( ciprofloxacin, levofloxacin,
moxifloxcin, gemifloxacin), khng sinh ging macrolide (azithromycin, telithromycin),
tetracycline (tetracyclin, doxycycline), v carbapenem (imipenem, meropenem, doripenem,
ertapenem). Trimethoprim-sulfamethoxazole cng hiu qu, mc d ang dn b khng.
Nhng ngi hay tip xc vi bnh nhn nhim H. influenzae serotype B nn c iu tr d
phng vi rifampin.
8 Haemophilus influenzae

La chn iu tr
Aminopenicillin + phong b -lactamase Amoxicillin/clavunate, ampicillin/sulbactam
Cephalosporin th h hai Cefuroxime
Hiu lc tng t
Ging macrolide Azithromycin, telithromycin
Ciprofloxacin, levofloxacin, moxifloxacin,
Quinolone
gemifloxacin
Carbapenem Imipenem, doripenem, meropenem, ertapenem
i khi c hiu lc
D phng serotype B
Rifamycin Rifampin
BORDETELLA PERTUSSIS
B. pertussis hnh cu trc khun rt nh gy bnh ho g (Hnh 11-9). tr em, bnh ny c c
trng bi nhng trng ho ngn v nhanh km theo th ngp, to nn ting whooop. Mc d bnh
thng hay gp tr, ho g ang ngy cng c nhn bit nhiu hn ngi ln nh l nguyn
nhn gy ra cc cn ho ko di vi tun hoc lu hn.
iu tr khng sinh cho bnh ho g vn cn tranh ci nhng thng c khuyn co s dng

trong thi k u ca bnh bi v n c th rt ngn thi gian b bnh v hn ch s ly lan.
Macrolides (azithromycin, clarithromycin, erythromycin) l nhng thuc c la chn cho c
tr em v ngi ln da trn tc dng ca n trn in vitro v c trn cc th nghim lm sng
(Bng 11-9). Nhng khng sinh hiu qu khc bao gm quinolone (ciprofloxacin, levofloxacin,
moxifloxacin), telithromycin, trimethoprim-sulfamethoxazole, v nhm tetracycline
(tetracycline, doxycycline). D phng sau khi tip xc vi mt macrolide nn c cn nhc cho
nhng ngi hay tip xc vi bnh nhn ho g.
MORAXELLA CATARRHALIS
M. catarrhalis l mt song cu Gram m thng gy vim tai gia, vim phi v vim xoang
(Hnh 11-10). Hu ht tt c cc chng ny u sn xut -lactamase khng c amoxicillin v
ampicillin. Khng sinh c hiu lc vi vi khun ny bao gm penicilin ph rng (piperacillin), -
lactam/phong b -lactamase (amoxicillin + clavunanate, ampicillin + sulbactam),
cephalosporin th h hai v th h ba (cefuroxime, ceftriaxone, cefotaxime), aminoglycosise
(gentamicin, tobramcin, amikacin), trimethoprim-sulfamethoxazole, tetracycline
121
(tetracycline, doxycycline), macrolide (azithromycin, chlarithromycin), v quinolone
(ciprofloxacin, levofloxacin, moxifloxacin).

10 Moraxella Catarrhalis

Penicillin ph rng Piperacillin
Quinolone Ciprofloxacin, levofloxacin, moxifloxacin
Macrolide Azithromycin, clarithromycin
ACINETOBACTER
Acninetobacter spp. l nhng trc khun hnh cn cu hay cu trc khun gy ra cc bnh nhim
khun mc phi ti bnh vin v cng ng. Cc bnh ny bao gm vim phi, nhim khun mu,
v nhim trng vt thng (Hnh 11-11). iu tr c th gp kh khn v nhiu chng khng
khng sinh. ng ch l cht phong b -lactamase sulbactam c tc dng dit khun vi vi
khun ny, v khng ngoi mong i, ampicillin-sulbactam c chng minh c hiu qu
trong iu tr nhim khun gy ra bi vi khun ny (Bng 11-11). Tng t, carbapenems
(imipenem, meropenem, doripenm), rifampin, v amikacin cng c th c hiu lc. Tuy nhin,
s khng vi cc khng sinh ny ang gia tng. Colistin v tigecycline thnh thong c dng
iu tr nhng chng khng vi cc khng sinh khc.

11 Acinetobacter Spp.

Rifamycin Rifampin
Aminoglycoside Amikacin
Clistin
Tetracycline Tigecycline
Cu hi
21. Vic s dng ampicillin v amoxicillin trong iu tr nhim khun Haemophilus influenzae
hin nay b hn ch bi sn xut mt___________bi nhiu chng vi khun.
22. Khng sinh c la chn iu tr nhim khun H. influenzae l
___________,___________,___________, hoc___________.
23. Khng sinh c la chn iu tr nhim khun Bordetella pertussis l
___________,___________, v___________.
24. Khng sinh khc cng c hiu lc vi B. pertussis bao gm ___________, ___________,
___________, v ___________.
25. Hu ht cc chun Moraxella catarrhalis u sn xut mt___________lm chng khng
vi -lactam.
26. Cht phong b -lactamase __________c hiu qu vi Acinetobacter baumannii.
C THM
Doern GV, Brueggemann AB, Pierce G, et al. Antibiotic resistance among clinical isolates of
Haemophilus in uenzae in the United States in 1994 and 1995 and detection of beta-
lactamasepositive strains resistant to amoxicillin-clavulanate: results of a national multicenter
surveillance study. Antimicrob Agents Chemother. 1997;41:292297.
Gordon KA, Fusco J, Biedenbach DJ, et al. Antimicrobial susceptibility testing of clinical isolates
of Bordetella pertussis from northern California: report from the SENTRY Antimicrobial
Surveillance Program. Antimicrob Agents Chemother. 2001;45:35993600.
Hewlett EL, Edwards KM. Clinical practice. Pertussisnot just for kids. N Engl J Med. 2005;352:
12151222.
Munoz-Price LS, Weinstein RA. Acinetobacter infection. N Engl J Med. 2008;358:12711281.
Murphy TF. Respiratory infections caused by non-typeable Haemophilus in uenzae. Curr Opin
Infect Dis. 2003;16:129134.
Murphy TF, Parameswaran GI. Moraxella catarrhalis, a human respiratory tract pathogen. Clin
Infect Dis. 2009;49:124131. Verduin CM, Hol C, Fleer A, et al. Moraxella catarrhalis: from
emerging to established pathogen. Clin Microbiol Rev. 2002;15:125144.
Vila J, Pachon J. Therapeutic options for Acinetobacter baumannii infections. Expert
OpinPharmacother. 2008;9:587599.
von Konig CH. Use of antibiotics in the prevention and treatment of pertussis. Pediatr Infect Dis
J. 2005;24:S66S68.
123
Chng 12: Vi khun k kh
SVY6. Hong Th Thu Trang, Hc vin Y Dc hc c truyn Vit Nam

Hiu nh: DS. V Th H
Ta nhng chin binh Trung C s dng my bn v cc v kh t kch cng ph phng

tuyn ca ta thnh ch, rt nhiu vi khun k kh lm tn thng c th ca chng ta bng vic
tit ra cc c t mnh. Vi c t trong s , v d nhng loi do cc chng thuc h Clostridia
sn sinh ra, l nhng c t mnh nht vi khun tng c bit n.
Vi khun k kh l nhng vi khun khng th sinh trng trong mi trng c oxy. Nhiu chng
trong s chng bnh thng c tr trong khoang ming, b my tiu ha, b phn sinh dc n.
Nhim khun thng din ra sau khi b mt nhu m ni tp trung nhiu vi khun b tn thng.
Bacteroides, Porphyromonas, v Prevotella spp. l nhng trc khun gram-m k kh thng gp
trong bnh cnh ny. Nhng vi khun k kh khc c tm thy ngoi t nhin v gy nhim trng
khi tnh c xm nhp vo c th chng ta. Clostridium spp., h vi khun gy cc bnh un vn,
ng c tht v hoi th sinh hi, l v d xc ng cho trng hp ny. Trong chng ny, chng
ta s tho lun v nhng sinh vt k trn, c bit nhn mnh vo hiu qu ca liu php khng
sinh s dng iu tr nhng nhim khun do chng gy ra.
Clostridia
Clostridia spp. l h vi khun Gram-dng, k kh, sinh nha bo. Chng gy nn nhiu bnh ph
bin v nguy him ngi, nh un vn, ng c tht v hoi th sinh hi. Thm vo , mt
chng ca h ny, Clostridium difficile, l nguyn nhn quan trng gy nhim khun tiu ha gy
ra bi dng thuc (iatrogenic gastrointestinal infections). Mc d tng i khc nhau nhng cc
bnh k trn u c im chung l gy nn bi c t v c t mnh.
Clostridium tetani l tc nhn gy Un vn (Hnh 12-1). Bnh ny c trng bi trng thi co cng
c lin tc, thng bao gm cng c nhai (cng hm) v cc c thn mnh. Cc triu chng xut
hin sau nhim nha bo un vn qua cc vt thng su. M hoi t to mi trng k kh thun
li cho s pht trin ca nha bo v gii phng c t un vn. c t ny c vn chuyn n
no v ty sng thng qua cc si trc thn kinh v gy nn co cng c ton thn v ri lon thn
kinh thc vt. Hng iu tr bnh un vn bao gm chm sc h tr tch cc, ch trng vo h h
hp v thn kinh c. S dng thuc khng c t trung ha c t un vn. Metronidazole v
penicilin l hai thuc khng sinh u tay. Vi s liu nghin cu ch ra rng s dng
Metronidazole em li kt qu tt hn (Bng 12-1).
Theo kinh in, bnh nhn b ng c tht khi n phi thc n c nhim nha bo Clostridium
botalinum, mc d nha bo cng c th xm nhp vo c th qua cc vt thng. C.botalinum,
cng nh C.tetani, sn sinh c t hng thn kinh gy cc tc dng ton thn. Tuy nhin c t
ng c tht dn n cc bnh l thn kinh s no v suy nhc hn l co cng c. V th, cc du
hiu v triu chng ca bnh ng c tht khc bit ng k vi un vn. Bnh nhn b Ng c
tht cn c chm sc h tr tch cc v s dng khng c t. Penicilin l thuc u tay v
metronidazole l thuc thay th hu ch (Bng 12-1).
BNG 12-1 Khng sinh trong iu tr nhim

khun do Clostridium spp.
Nhm Khng sinh Khng sinh
Thuc u tay
Penicilin t nhin Penicilin G*
Metronidazole
* Ngoi l: Khng nn dng Penicilin trong iu tr
Clostridium difficile. Nn dng Vancomycin ng
ung hoc metronidazole ng ung.
125
Clostridium perfringensis l nguyn nhn gy hoi th sinh hi, mt nhim khun nguy him, tin
trin nhanh xy ra trn m mm, c, cc t chc su (Hnh 12-1). Hng iu tr bao gm can
thip ngoi khoa ct b t chc cng vi liu php khng sinh. Penicilin phi hp vi mt trong
cc thuc sau: clindamycin, tetracylin hoc metronidazole thng c s dng (Bng 12-1).
Khng nh nhng loi cn li trong h Clostridia, bnh l do C. difficile gy ra khng lin quan
n chn thng hay mc phi do n ung m lin quan n s dng khng sinh. Bnh thng, h
vi khun ch tn ti trong i trng vi s lng ngn cn s xm ln ca C. difficile. Tuy
nhin sau khi s dng khng sinh, nhiu thnh phn ca h ny b tiu dit to iu kin cho s
sinh trng rm r ca C. difficile. Clindamycin l mt trong nhng khng sinh dng nh l vn
gy ra bnh l do C. difficile. Nhim khun do C. difcile s dn ti nhiu hnh thi bnh khc
nhau t tiu chy th nh ti vim i trng gi mc cp tnh v e da tnh mng. Hng iu
tr bao gm: (nu c th) dng khng sinh l cn nguyn ca bnh v s dng khng sinh khng
Clostridium. Metronidazole ng ung l la chn cho th nh n va. Vancomycin ng
ung khng b hp thu ng k vo mu, do t c nng cao ng tiu ha nn c
khuyn co s dng vi th nng (Bng 12-1).
IM QUAN TRNG
S tin trin cc bnh gy ra bi C. diffucile ch yu lin quan n clindamycin, ampicillin v
cephalosphrin. Trong khi ampicillin v cephalosphorin, hai loi khng sinh thng xuyn c ch
nh, l nguyn nhn l gii cho t l ln cc bnh do C. difficile, th mi quan h gia nhng bnh
cnh ny vi clindamycin dng nh c th hn. Nh nhng chng k kh khc, C. difficile v
c bn nhy cm vi clindamycin. Tuy nhin nhng dng C. difficile gy dch tiu chy bnh vin
c xu hng khng khng sinh ny. Bi vy, bn cnh vic c ch h vi khun ch, clindamycin
cn khin C. diffucile nhn ln v gy hi cho i trng.
Johnson S, Samore MH, Farrow KA, et al. Epidemics of diarrhea caused by a clindamycin-
resistant strain of Clostridium diffi cile in four hospitals. N Engl J Med. 1999;341:16451651.
CU HI LNG GI
1. Clostridium spp l trc khun , sinh , gram .
2. Trong phn ln cc nhim khun do Clostridium spp, thuc u tay c s dng l
v .
3. Vim i trng do C. difficile c iu tr bng ng ung v
ng ung.
THAM KHO
Ahmadsyah I, Salim A. Treatment of tetanus: an open study to compare the effi cacy of procaine
penicillin and metronidazole. Br Med J (Clin Res Ed). 1985;291:648650.
Alexander CJ, Citron DM, Brazier JS, et al. Identifi cation and antimicrobial resistance patterns of
clinical isolates of Clostridium clostridioforme, Clostridium innocuum, and Clostridium ramosum
compared with those of clinical isolates of Clostridium perfringens. J Clin Microbiol.
1995;33:32093215.
Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile
infections in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA)
and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol.
2010;31:431455.
Darke SG, King AM, Slack WK. Gas gangrene and related infection: classification, clinical
features and aetiology, management and mortality. A report of 88 cases. Br J Surg. 1977;64:104
112.
Sobel J. Botulism. Clin Infect Dis. 2005;41:11671173.
127
Trc khun Gram m k kh
Nhiu chng Trc khun gram-m k kh c tr vi mt cao trong khoang ming, h tiu ha,
m o ca con ngi, bao gm Bacteroides (quan trng nht l chng Bacteroides fragilis),
Prevotella v Porphyromonas spp. Khi gp iu kin thun li chng s gy nn bnh l nha chu,
vim phi mng phi, vim vng chu, abces bng (Hnh 12-2). c tnh ca chng c gia
tng khi c mt cc chng vi khun khc v v vy nhng sinh vt ny thng lin quan n nhim
a trng.
Trc khun k kh gram-m, c bit l chng B. fragilis, thng tit ra -lactamase phn hy
penicillin v cephalosphorin. Tuy vy, nhm carbapenem v vi cephalosporin (nh cephamycin,
cefotetan v cefoxitin) vn vng bn trc -lactamase. Tng t, cc enzyme -lactamase ny b
kh hot tnh bi cc cht c ch -lactamase.
iu tr nhim khun k kh thng theo kinh nghim v da trn kt qu quan st, rng trc
khun gram m k kh gn nh u nhy cm vi -lactam/hp cht c ch -lactamase
ampicillin-sulbactam, piperacillin- tazobactam, ticarcillin-clavulanate), nhm carbapenem
(imipenem, meropenem, doripenem, ertapenem) v metronidazole (Bng 12-2).
Chloramphenicol cng em li hiu qu iu tr cao, nhng b hn ch s dng bi c tnh ca
thuc. Nhng khng sinh khc cng c tc dng tt tr trc khun gram-m k kh bao gm
clindamycin, piperacillin, tigecycline, cng nh mt vi thuc thuc nhm cephalosporin
(cefotetan, cefoxitin) v nhm quinolone (moxifloxacin).
BNG 12-2 Khng sinh trong iu tr nhim khun do Bacteroides,

Prevotella v Porphyromonas Spp.
Nhm Khng sinh Tn khng sinh
La chn hng u
-lactam/ hp cht c ch -lactamase Ampicillin-sulbactam, piperacillin-tazobactam,
ticarcillin-clavulanate
Carbapenems Imipenem, meropenem, doripenem, ertapenem
Metronidazole
La chn cu cnh
Clindamycin
Cephalosporin th h hai Cefotetan, cefoxitin
Penicilin ph rng Piperacillin
Quinolones Moxifloxacin
Thuc tng t Tetracycline Tetracycline
Chloramphenicol
CU HI LNG GI:
4. , , v spp. l nhng trc khun gram-m k kh
quan trng trn lm sng.
5. Bn loi khng sinh c tc dng vt tri chng li trc khun gram-m k kh l ,
, , v .
6. Nhng khng sinh khc cng c tc dng tt chng li trc khun gram-m k kh bao gm
, , , v . .
TI LIU THAM KHO:

Aldridge KE, Ashcraft D, Cambre K, et al. Multicenter survey of the changing in vitro
antimicrobial susceptibilities of clinical isolates of Bacteroides fragilis group, Prevotella,
Fusobacterium, Porphyromonas, and Peptostreptococcus species. Antimicrob Agents Chemother.
2001;45:12381243.
Snydman DR, Jacobus NV, McDermott LA, et al. National survey on the susceptibility of
Bacteroides fragilis group: report and analysis of trends for 19972000. Clin Infect Dis. 2002;35(
suppl 1):S126S134.
Vedantam G, Hecht DW. Antibiotics and anaerobes of gut origin. Curr Opin Microbiol.
2003;6:457461
129
Chng 13. Vi khun khng in hnh
Ngi dch: Trn Th Hng Ngoan SVD5 - H Dc HN
Hiu nh: DS. V Th H
Nh cp, c nhiu vi khun khng c xp vo nhm vi khun Gram m; Gram dng, vi

khun k kh, xon khun, mycobacteria. Nhng vi khun ny s c tho lun ti chng ny v
c coi l vi khun khng in hnh bi hu ht chng u kh c th pht hin c bng cc
phng php quen thuc nh nhum Gram hay rt kh c th nui cy trong phng th nghim.
Mc d s phn loi ny khng phi l hon ho nhng n cng l mt cch xem xt liu php
khng sinh ph hp i vi nhm vi khun a dng ny. Cc vi khun c tho lun trong nhm
ny bap gm: Clamydia spp, Myclophasma spp, Legionella pneumophila, Brucella spp.,
Francisella tularensis, and Rickettsia spp.
Nhiu vi khun trong nhm ny c th gy tn thng hoc cht cc t bo ca c th ngi bng

chnh cc hot ng sng v s nhn ln ca chng trong cc t bo. Theo cch ny, chng ging
nh nhng ngi cng nhn m Trung c, nhng ngi to ra nhng ng hm pha di
nhng bc tng c phng th kin c thc hin nhng cuc tn cng t bn trong lu i.
Do cc vi khun ny sng trong ni bo, cc khng sinh iu tr trong nhim trng cc vi khun
ny phi c kh nng thm tt vo trong t bo.
1. Clamydia
Vi khun thuc chi clamydia l cc vi khun ni bo bt buc, pht trin tip din ga hai th: th
c bn (elementary body) c th sng st khi b phng thch ra ngoi ngoi bo v th li
(reticulate body) thch hp nhn ln bn trong t bo. Trc y chi chlamydia gm 3 vi khun
quan trng trn lm sng: Chlamydia trachomatis, Chlamydia pneumoniae, v Chlamydia psittaci.
Tuy nhin nhng quan st gn y cho thy 2 loi mi y ca C.trachomatis kh khc bit v h
xp chng vo mt chi ring c gi l Chlamydophila.
Chlamydia trachomatis l mt trong nhng nguyn nhn ch yu gy ra cc bnh ly truyn qua

ng tnh dc v cng l nguyn nhn hng u gy m la mt s ni trn th gii. Chlamydia
pneumoniae l tc nhn ph bin gy vim phi cng ng trong khi Chlamydia psittaci li l
nguyn nhn gy bnh st vt- mt loi vim phi rt him thng xut pht t cc loi chim k
l.
Do Chlamydia and Chlamydophila spp l nhng vi sinh vt ch sng trong ni bo nn cc khng

sinh iu tr cc bnh nhim khun do cc vi khun ny gy ra phi thm c vo ni bo vi t
l cao. Cc nhm khng sinh c c th s dng bao gm: nhm macrolid ( azithromycin,
erythromycin), tetracyclines (doxycycline, tetracycline), v mt s quinolone ( bng 13-1).
Trong khi , ofloxacin v levofloxacin c khuyn co trong iu tr nhim khun do
Chlamydia trachomatis, moxifloxacin v gemifloxacin c tc dng tt nht i vi Chlamydophila
pneumoniae. Telithromycin cng c tc dng vi Chlamydophla pneumonae. Do chlamydia v
Chlamydophila spp khng c peptidoglycan nn cc - lactam thng khng hiu qu, nhng nu
nguyn nhn khng r rng, amoxicillin vn c th c s dng. Do tnh an ton ca n khi s
dng cho ph n c thai, amoxicillin thng c s dng trong nhim khun Chlamydia
trachomatis vi cc bnh nhn ny. Cn lu rng clindamycin c tc dng trn vi khun
Chlamydia trachomatis v c s dng trong mt s phc khng sinh iu tr vim vng chu.
Bng 13-1 Khng sinh iu tr nhim khun do chlamydia v chlamydophila

spp.
Nhm khng Khng sinh
sinh
Tetracylin Tetracycline, doxycycline
Macrolid Azithromycin, erythromycin, telithromycin (Chlamydophila
pneumonia)
Quinolone Ofloxacin (Chlamydia trachomatis), levofloxacin (Chlamydia
trachomatis), moxifloxacin (Chlamydophila pneumoniae),
gemifloxacin (Chlamydophila pneumoniae)
Ph n c thai
Macrolid Azithromycin, erythromycin
Aminopenicillin Amoxicillin
Cu hi:
1) 3 nhm khng sinh c tc dng tt nht trn Chlamydophila trachoatis l: .
2) Chlamydia v Chlamydophila spp khng c peptidoglycan do khng vi nhiu .., mc d
cha c nguyn nhn r rng nhng c mt s tc dng vi Chlamydophila trachoatis.
c thm:
Adimora AA. Treatment of uncomplicated genital Chlamydia trachomatis infections in adults. Clin
Infect Dis. 2002;35(suppl 2):S183S186.
Hammerschlag MR. Pneumonia due to Chlamydia pneumoniae in children: epidemiology,
diagnosis, and treatment. Pediatr Pulmonol. 2003;36:384390.
Kirchner JT. Psittacosis. Is contact with birds causing your patients pneumonia? Postgrad Med.
1997;102:181182, 187188, 193194.
Workowski KA, Berman S, Centers for Disease Control and Prevention. Sexually transmitted
diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59:1110.
131
2. Mychoplasma
Cc vi khun mychoplasma c th coi l vi khun sng t do nh nht. Mc d nhiu chng c
th gy bnh cho ngi nhng Mychoplasma pneumoniae l tc nhn ph bin nht. Nhng vi
khun ny ch pht trin c trong c th vt ch hoc trong cc phng th nghim vi cc iu
kin thch hp l cc nguyn nhn ph bin gy vim phi cng ng. Cc nhm khng sinh iu
tr hiu qu trong trng hp ny bao gm: macrolide ( azithromycin, clarithromycin,
erythromycin), tetracycline (doxycycline, tetracycline) (Bng13-2). Mt s khng sinh khc
cng c hiu qu: quinolones (levofloxacin, moxifloxacin, gemifloxacin) v telithromycin.
Mychoplasma khng c vch t bo nn -lamtam khng c tc dng i vi cc vi khun ny.
Bng 13-2 Khng sinh iu tr nhim khun do mychoplasma
Nhm khng Khng sinh

sinh
Macrolid azithromycin, clarithromycin, erythromycin
Tetracylin Tetracycline, doxycycline
Quinolone levofloxacin, moxifloxacin, gemifloxacin
Cu hi
3) 3 nhm khng sinh c tc dng tt nht i vi Mychoplasma pneumoniae l:..
4) M.pneumoniae khng c vch t bo nn .. khng c tc dng.
c thm:
Mandell LA, Bartlett JG, Dowell SF, et al. Update of practice guidelines for the management of
community-acquired pneumonia in immunocompetent adults. Clin Infect Dis. 2003;37:1405
1433. Taylor-Robinson D, Bbar C. Antibiotic susceptibilities of mycoplasmas and treatment of
mycoplasmal infections. J Antimicrob Chemother. 1997;40:622630. Communityacquired
pneumonia.
3. Legionella
Legionella spp. l cc vi khun sng trong mi trng nc t nhin hoc cc h thng ng ng
nc. Nhiu vi khun thuc chi legionella c th gy bnh cho ngi trong hay gp nht l L.
pneumophila. Nhng vi khun ny gy bnh Legionaires - mt dng vim phi nng hoc st
potiac mt dng bnh nh hn v khng nh hng n chc nng h hp. Legionella c th gy
vim phi cng ng hoc vim phi mc phi ti bnh vin. Ti phi, cc vi khun legionella b
nut vo bn trong cc i thc bo v nhn ln trong . Kt qu l din bin ca bnh thng
nng v thng km theo cc du hiu v triu chng ton thn nh: st cao, n lnh, bun nn,
nn, tiu chy v khng tnh to. Cc nghin cu trong phng th nghim cho thy bng chng
ca suy gim chc nng gan, thn v h Na+ mu. Cc vi khun legionella c tr trong cc i
thc bo v vy cn s dng cc thuc c kh nng thm vo v c tc dng tt trong thc bo nh
macrolid, tetreacyclin, quinolone. Cc khng sinh nn la chon : azithromycin, levofloxacin, v
moxifloxacin (Bng 13-3). Ngoi ra c th s dng cc khng sinh sau: ciprofloxacin,
gemifloxacin, clarithromycin, telithromycin, erythromycin, v doxycycline.
Bng 13-3 Khng sinh iu tr nhim khun do legionella Spp
Nhm khng Khng sinh

sinh
La chn u tay
Macrolid Azithromycin,
Quinolone Levofloxacin, moxifloxacin
La chn thay th
Macrolid Erythromycin, clarithromycin, telithromycin
Quinolone ciprofloxacin, gemifloxacin
Tetracylin Doxycycline
Cu hi:
5) Khng sinh iu tr nhim khun legionella bao gm: ., ., v .
6) Cc vi khun legionella ch yu nm trong , v vy cc khng sinh phi vo c v tiu
dit vi khun.
c thm:
Blzquez Garrido RM, Espinosa Parra FJ, Alemany Francs L, et al. Antimicrobial chemotherapy
for Legionnaires disease: levofl oxacin versus macrolides. Clin Infect Dis. 2005;40:800806.
Roig J, Rello J. Legionnaires disease: a rational approach to therapy. J Antimicrob Chemother.
2003;51:11191129.
Sabri M, Pedro-Botet ML, Gmez J, et al. Fluoroquinolones vs macrolides in the treatment of
Legionnaires disease. Chest. 2005;128:14011405.
Yu VL, Greenberg RN, Zadeikis N, et al. Levofl oxacin effi cacy in the treatment of
communityacquired legionellosis. Chest. 2004;125:21352139.
4. Brucella
Brucella spp. l cc trc khun gram m nh v gy brucellosis, mt bnh trn ng vt v i khi
ly sang ngi. Cc chng hay gy bnh trn ngi nht l Brucella melitensis, Brucella abortus,
Brucella suis, v Brucella canis. Tip xc gn vi ng vt, s dng sa cha tit khun hoc ph
mai l cc yu t nguy c gy bnh. Triu chng ca bnh bao gm: st, v m hi, mt mi, kh
chu v bing n. Brucelsosis thng kh chn on v nu khng iu tr n c th ko di vi
tun hoc vi thng. Nhim khun ko di c th gy cc biu hin ti ch nh: vim khp
133
(osteoarthritis), sacroiliitis (vim khp gia xng chu v t sng), hoc vim mo tinh hon v
tinh hon (epididymo-orchitis).
Cc vi khun Brucella ny sng v nhn ln trong cc t bo thc bo. Do , phc iu tr
brucellosis phi c doxycycline- khng sinh thm tt vo bn trong cc t bo . Phc u tin
l doxycycline kt hp vi rifampicin hoc doxycycline kt hp vi steptomycin hay
gentamycin ( bng 13-4). Cc quinolone (ciprofloxacin, levofloxacin, moxifloxacin) cng c
hiu qu khi s dng kt vi cc khng sinh khc nh rifampicin, tuy nhin kinh nghim cn t.
Trimethoprim-sulfamethoxazole v rifampin c khuyn co cho tr em v trimethoprim-
sulfamethoxazole kt hp rifampin hay rifampin n c c khuyn co dnh cho ph n c
thai- nhng i tng c chng ch nh vi doxycycline. Qu trnh iu tr phi ko di (VD: 6
tun) v bnh nhn c th b ti pht.
Bng 13-4 Khng sinh iu tr nhim khun do Brucella

spp.
La chn u tay
Tertracyclin + rifampicin Doxycycline + rifampicin
Tetracycline + aminoglycosid Doxycycline + gentamycin,
Doxycycline + streptomycin
La chn thay th
Nhm sulfamid Trimethoprim-sulfamethoxazole
Quinolone ciprofloxacin, levofloxacin, moxifloxacin
Lch s:
Brucellosis b xem l nguyn nhn gy ra mt trong nhng thm ha ti t nht ca hi qun trong
thi bnh, cuc va chm gia tu HMS Victoria v HMS Camperdown ngoi khi b bin Syria
nm 1893. Cuc va chm nh chm tu Victoria ca Hm i a Trung Hi Anh lm cht 358
thy th. Mt s nh nghin cu tin rng thuyn trng ca nhng chic tu ny nhim
brucellosis- mt loi c hu mt s vng ca a Trung Hi vo thi im . iu ny lm
gim bn n ca h vi s vic ny.
Cu hi:
7) 4 khng sinh thng s dng nht trong iu tr brucellosis l:
8) Phc kt hp thng c dng iu tr brucellosis. 3 phc thng gp nht l :
Doxycycline + , Doxycycline + ., Doxycycline +
9) Do Doxycycline v quinolone khng c khuyn co cho ph n c thai, c s dng cho
cc bnh nhn ny khi h mc brucellosis.
c thm:
Ariza J, Gudiol F, Pallares R, et al. Treatment of human brucellosis with doxycycline plus
rifampin or doxycycline plus streptomycin. A randomized, double-blind study. Ann Intern
Med. 1992;117:2530.
Franco MP, Mulder M, Gilman RH, et al. Human brucellosis. Lancet Infect Dis. 2007;7:775786.
Pappas G, Akritidis N, Bosilkovski M, et al. Brucellosis. N Engl J Med. 2005;352:2325 2336.
5. Francisella tularensis
Francisella tularensis, trc khun gram m ch yu gy nhim trng ng vt, l nguyn nhn
gy tularemia. Francisella c th ly lan bng nhiu cch nh nhim trc tip do tip xc vi hoc
n tht ng vt nhim khun hoc gin tip qua cc vt cn ca cn trng, phi nhim vi nc
hay bn nhim khun, hoc do ht phi tc nhn. Ht phi F. tularensis c th gy ra bnh nng do
n c phn loi nh mt v kh sinh hc. Nhim tularemia bao gm cc th: th lot da
(ulceroglandular), th da khng lot (glandular), th mt (oculoglandular), th hu
hng(oropharyngeal), th thng hn (typhoidal), th phi (pneumoic). th lot da, bnh nhn

thng c tn thng da ti v tr ly nhim ( VD: vt cn ca cn trng) v lot cc hch xung
quanh. Th da khng lot tng t th lot da nhng khng c du hiu lot. Bnh nhn th
thng hn thng st cao v nhim trng mu. Nhng bnh nhn th phi c du hiu v triu
chng ca vim phi. cc bnh nhn th hu hng thng c vim hu hng v sng cc hch
bch huyt. Th hch mt xut hin khi vi khun qua nim mc mt, gy vim kt mc. Mc d
F.tularensis l mt vi khun ni bo khng bt buc nhng streptomycin vn l khng sinh hiu
qu nht (Bng 13-5). L do s dng streptomycin vn cha r rng nhng c th l do ch cn
tiu dit cc vi khun ngoi bo cng iu tr bnh. Gentamycin cng thng c s dng
thay th cho streptomycin v n c sn mc d hiu qu thp hn. Tetracyclin, doxycyclin vad
chloramphenicol cng c th dng thay th.
Bng 13-5 Khng sinh iu tr nhim khun do F.tularensis

La chn u tay
Aminoglycosid streptomycin
La chn thay th
Aminoglycosid Gentamycin
Tetracyclin Tetracycline, doxycycline, cloramphenicol
Cu hi:
10) Khng sinh c la chon iu tr tularemia l :
11) Do tnh c sn, thng c s dng thay th cho streptomycin trong iu tr tularemia.
12) Cc khc sinh khc c s dng trong iu tr tularemia bao gm:
c thm:
Ellis J, Oyston PC, Green M, et al. Tularemia. Clin Microbiol Rev. 2002;15:631646.
Enderlin G, Morales L, Jacobs RF, et al. Streptomycin and alternative agents for the treatment of
tularemia: review of the literature. Clin Infect Dis. 1994;19:4247.
Evans ME, Gregory DW, Schaffner W, et al. Tularemia: a 30-year experience with 88 cases.
Medicine (Baltimore). 1985;64:251269.
6. Rickettsia
C nhiu loi vi khun Rickettsia c th gy bnh cho ngi. Cc vi khun ny nh, c cu trc v
t bo ging nh vi khun gram m v sng ni bo bt buc. Cc triu chng ph bin ca nhim
khun rickettsial l : st, au u v pht ban. Bnh thng ly lan qua cc vt ch trung gian l
cc ng vt chn t. Cc th bnh bao gm: st ni mn ni (Rickettsia rickettsii), st ni
mn a Trung Hi (Rickettsia conorii), rickettsialpox (Rickettsia akari), st ban chy rn
(Rickettsia prowazekii), st ban b chut (Rickettsia typhi) v st do m (gy ra bi cc vi khun
c lin quan cht ch n Orientia tsutsugamushi).
Hu ht cc bnh gy ra do rickettsial c iu tr bng doxycyclin- khng sinh c kh nng

thm tt vo ni bo ( bng 13-6). Doxycyclin cn c khuyn co cho tr em vi mt s th ca
rickettsial do qu trnh iu tr ngn nn khng gy ra tc dng bt li trn xng v rng.
Tetracyclin cng thng c s dng. Mc d khng hiu qu bng tetracycline,
cloramphenicol cng c th s dng thay th cho ph n c thai. Ciprofloxacin cng c th s
dng iu tr st ni mn ni , st ni mn a Trung Hi v rickettsialpox.
135
Lch s:
Bnh rickettsial chy rn c cho l nguyn nhn khin i qun ca Napoleon suy yu khi rt
qun khi Nga. Gn y, cc nh nghin cu xc minh c vic ny nh pht hin ra DNA
ca Rickettsia prowazekii trong ty rng thi th ca qun lnh c chn Lithiania
Bng 13-6 Khng sinh iu tr nhim khun do
Rickettsia prowazekii
La chn u tay
Tetracycline Doxycycline, tetrecycline
La chn thay th
Cloramphenicol
Cu hi:
13) Thuc c la chn iu tr rickettsial:
14) Cc khng sinh khc cng c th tiu dit rickettsial: , . v .
c thm:
Maender JL, Tyring SK. Treatment and prevention of rickettsial and ehrlichial infections.
Dermatol Ther. 2004;17:499504.Parola P, Paddock CD, Raoult D.
Tick-borne rickettsioses around the world: emerging diseases challenging old concepts. Clin
Microbiol Rev. 2005;18:719756.
Chng 14: Xon khun

Dch: Hong Th Hng Thanh, SV D5, H Dc H Ni
Mail: thanhhongdkh@gmail.com
Hiu nh: DS. V Th H
Xon khun l vi khun hnh xon hoc xon c. Mt s loi vi khun trong nhm ny rt quan
trng v mt y hc, nhng hai vi khun ni ring thng gp bi cc bc s. Chng l Treponema
pallidum, nguyn nhn ca bnh giang mai ly qua ng tnh dc, v Borrelia burgdorferi, cn
nguyn ca bnh Lyme. Leptospira interrogans gy ra mt bnh t gp nhng nghim trng gi l
trng xon mc cu. Trong phn ny, cc vi khun v iu tr khng sinh ca cc bnh nhim
trng do chng gy ra s c tho lun.
Treponema pallidum
Giang mai l mt bnh ly truyn qua ng tnh dc do xon khun Treponema pallidum.
Nhim trng cp tnh, c gi l giang mai s cp, thng c biu hin bng s hin din ca
mt sng ch nhim (Hnh 14-1). Cc sng t cha lnh, nhng vi tun sau , cc du hiu v
triu chng ca bnh giang mai th cp c th tin trin. Chng bao gm pht ban da, cc mng
nhy, st, kh chu v ni hch. Cc biu hin ca bnh giang mai th cp thng c gii quyt
nhng d b ti pht. Tuy nhin, ti mt s im, cc c th thng bc vo giai on bnh c
gi l giang mai tim n, trong khng c bng chng r rng ca nhim trng. Giang mai tim
n c chia thnh hai loi: giang mai giai on sm, c nh ngha l nhim trng xy ra
trong nhng nm trc , v giang mai giai on mun, c nh ngha l giang mai tim n
trong nhim trng xut hin lu hn 1 nm. S khc bit ny l quan trng bi v phc
iu tr khng sinh khc nhau cho hai giai on ca bnh. Mt thi gian sau khi nhim bnh ln
u tin, mt s c nhn s pht trin bnh cnh lm sng th hin bnh mn tnh nng dn ln v
c gi l giang mai mun hoc giang mai cp ba. Giang mai cp ba thng c biu hin nh
bt thng v tim mch hoc s hnh thnh giang mai trong da hoc c quan ni tng. lm cho
vn thm phc tp, cuc xm chim h thng thn kinh trung ng ca T. pallidum c th xy
ra trong bt k giai on no ca bnh giang mai. Kt qu ny trong giang mai thn kinh, c th c
dng ca bnh mng no hoc bnh mch mu mng no, c lin quan n mt, bnh lit ni
chung, bnh ng mch lng, hoc bnh h thng thn kinh trung ng.
137
Bnh l h thng thn kinh
trung ng
(giang mai thn kinh)
Pht ban & hch Bnh tim mch

(giang mai th cp) (giang mai cp ba)
S hnh thnh giang mai

(giang mai cp ba)
(giang mai cp ba) Sng sinh dc
(giang mai chnh)
HNH 14.1. Cc v tr nhim trng gy ra bi Treponema pallidum.

V T. pallidum khng th c nui cy trong ng nghim, hu ht nhng g c bit v n l
nhy cm vi khng sinh da trn th nghim ngi. iu ny ch ra rng penicillin kh hiu
qu i vi sinh vt ny (Bng 14-1). Cc ng dng thuc v thi gian iu tr thay i theo giai
on v loi bnh giang mai cng nh cc yu t vt ch. V d giang mai s cp, th cp, v thi
k u bnh giang mai tim n c iu tr bng mt liu tim bp benzathine penicillin (xem
bng "IM QUAN TRNG"). Ngc li, giang mai giai on mun v giang mai cp ba c
iu tr bng ba mi tim benzathine penicillin c a ra trong khong 1 tun. Giang mai thn
kinh c iu tr vi 10 n 14 ngy tim tnh mch penicillin G. La chn thay th cho cc bnh
nhn b d ng vi penicillin bao gm tetracycline, doxycycline, hoc ceftriaxone. D liu h tr
cho vic s dng cc thuc thay th l thiu i vi mt s tnh hung lm sng c th; do , gy
t v iu tr tip theo vi penicillin l liu php ti u c xem xt trong mt s bnh nhn d
ng vi penicillin, nh ph n c thai.
Bng 14-1 Cc tc nhn khng sinh iu tr cc nhim trng gy ra bi
Treponema pallidum
Loi khng sinh Khng sinh
Tc nhn la chn
Penicillins t nhin Penicillin G (bao gm benzathine penicillin)
La chn thay th Tetracycline, doxycycline
Tetracyclines
Cephalosporin th h ba Ceftriaxone
IM QUAN TRNG
Benzathine Penicillin l mt dng tr penicillin bao gm cc mui benzathine tetrahydrat ca
penicillin G. Trong c th, cc hp cht c thy phn t t gii phng penicilin G. Nh

vy, nng thp nhng lu di ca penicillin c th t c sau mt liu tim bp duy nht.
Ty thuc vo liu lng, nng c th c pht hin t 1 n 4 tun sau khi tim. Nh vy,
dng penicillin ny hu ch trong vic iu tr vi khun cc k nhy cm vi penicillin (ngha l,
c nng c ch ti thiu thp) nhng cn phi tip xc ko di. Treponema pallidum l mt v
d ca mt sinh vt nh vy.
CU HI
1. Khng sinh c la chn cho giang mai l ____________.
2. ng dng v thi gian iu tr cho bnh giang mai ph thuc vo ____________ ca bnh.
3. Tim bp ____________ ____________ cho php gii phng chm Penicillin vo vng tun
hon trong vi ngy.
C THM
Centers for Disease Control and Prevention, Workowski KA, Berman JM. Sexually transmitted
diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006;55:194.
Golden MR, Marra CM, Holmes KK. Update on syphilis: resurgence of an old problem. JAMA.
2003;290:15101514.
Borrelia burgdorferi
Borrelia burgdorferi gy ra bnh Lyme, bnh truyn qua vector ph bin nht Hoa K v Chu
u. Tng t nh bnh giang mai, bnh Lyme din ra trong nhiu giai on. Giai on 1ca bnh
xy ra ngay sau khi gy nhim vi khun vo vt ch thng qua mt vt cn. iu ny dn n pht
ban da hnh khuyn c trng c gi l ban migrans, xy ra ti v tr vt cn (Hnh 14-2).
Giai on 2 ca bnh xy ra vi ngy n vi tun sau , khi cc sinh vt c lan ta. Bnh
nhn c th c pht ban da th cp, hch to, vim mng no v nhng pht hin v thn kinh, hoc
bng chng v tn thng tim. Vi thng n vi nm sau , bnh nhn c th pht trin bnh
giai on 3, c c trng bi vim khp hoc bt thng thn kinh mn tnh nh suy gim nhn
thc.
Cc la chn iu tr cho hu ht cc biu hin ca bnh Lyme ngi 8 tui tr ln v ph
n khng mang thai l doxycycline ng ung (Bng 14-2). Tc nhn thay th tt nht c
nghin cu l amoxicillin. La chn thay th khc bao gm cefuroxime ng ung hoc
erythromycin ng ung. C th vi tn thng thn kinh hoc tn thng tim nghim trng
nn c iu tr bng khng sinh tim tnh mch nh ceftriaxone hoc penicilin G. Cc quan st
trong ng nghim v trong c th sng ch ra rng rifampin, quinolones, aminoglycosides, v
cephalosporin th h u tin khng c hiu qu chng li cc sinh vt ny.
CU HI
4. Khng sinh c la chn bnh Lyme l ____________.
5. Cc khng sinh khc c s dng iu tr giai on 1 ca bnh Lyme bao gm
____________, ____________ v ____________.
6. Bnh Lyme vi tn thng thn kinh hoc tn thng tim nghim trng cn c iu tr vi
tim tnh mch ____________ hoc ____________.
139
Bnh h thng thn
kinh trung ng
Bnh tim
Pht ban
Vim khp
HNH 14.2. Cc v tr nhim trng gy ra bi Borrelia burgdorferi.

Borrelia burgdorferi
Tc nhn u tin
Tetracyclines Doxycycline
Tc nhn th hai
Aminopenicillins Amoxicillin
Thay th
Macrolide Erythromycin
Bt thng v thn kinh v tn thng tim nghim trng
C THM
Steere AC. Lyme disease. N Engl J Med. 2001;345:115125.
Wormser GP, Nadelman RB, Dattwyler RJ, et al. Practice guidelines for the treatment of Lyme
disease. The Infectious Diseases Society of America. Clin Infect Dis. 2000;31(suppl 1):114.
Leptospira interrogans
Leptospira interrogans l mt xon khun mng gy ra bnh nhim trng do leptospira ly t

ng vt sang. Vi khun ny c thi ra trong nc tiu ca nhiu loi vt nui v hoang d; thu
nhn bi nhng ngi sau khi tip xc trc tip hoc gin tip vi nc b nhim, bn, hoc m
ng vt. C th vi bnh do leptospira c th c s hin din vi mc bnh nghim trng khc
nhau, t bnh cn lm sng n suy a ph tng dn n t vong. Nhng ci vi bnh nng
thng c hai giai on bnh gm st ban u, au u, chy mu kt mc, v au c sau h st v
ti pht sau vi tn thng gan, thn, hoc mng no (Hnh 14-3).
Leptospirosis nh thng c iu tr bng khng sinh ng ung, nh doxycycline hoc
amoxicillin. Bnh va hoc nng c iu tr bng thuc tim tnh mch nh penicillin G,
ceftriaxone hoc ampicillin (Bng 14-3).
Leptospira interrogans
Bnh nh
Tetracyclines Doxycycline
Aminopenicillins Amoxicillin
Bnh trung bnh v nng
Aminopenicillins Ampicillin
CU HI
7. Nh cc xon khun khc, Leptospira interrogans nhy cm vi penicillin /
amoxicillin v ____________.
8. ____________ v ____________ l tc nhn c la chn cho leptospirosis nh.
9. Vi leptospirosis nng, tim tnh mch ____________, ____________ hoc ____________
c khuyn co.
C THM
Bharti AR, Nally JE, Ricaldi JN, et al. Leptospirosis: a zoonotic disease of global importance.
Lancet Infect Dis. 2003;3:757771.
Levett PN. Leptospirosis. Clin Microbiol Rev. 2001;14:296326.
141
St
Vim mng no
Vim gan
Suy thn
HNH 14.3. Cc v tr nhim trng gy ra bi Leptospira interrogans.

PHN IV. IU TR KINH NGHIM
Chng 15: Mycobacteria

Dch: L V K Nam, BV Nng
Hiu nh: DS. V Th H
Nhn chung, cc loi vi khun Mycobacterium, l cc loi vi sinh vt sinh trng chm v
gy nn cc bnh mn tnh. Thng thng, bnh nhn b nh hng bi nhim trng vi khun
Mycobacteria do c th ngy cng yu t v hao mn do qu trnh nhim khun xy ra mt cch
chm chp v t t tin trin v kt qu l c th bnh nhn tr nn suy nhc v hc hc.
phng din ny, cc bnh nhim khun Mycobacteria ging nh l mt cuc vy hm ngy cng
c m rng trong c th hn l mt cuc tn cng tng lc tn ph ton b h thng phng
th ca c th.
Cc vi khun Mycobacteria l mt nhm vi khun c kh nng to thnh t bo giu lipids v acid

bo. Mt loi acid bo l mycolic acid c bit phong ph v chim khong 60% khi lng mng
t bo ca vi khun. Mc d cc vi khun Mycobacteria c cu trc mng t bo Gram dng,
lng lipid cao trong mng t bo ngn nga s xm nhp ca thuc nhum Gram, v do k
thut nhum Gram khng cho php quan st c hnh nh ca vi khun di knh hin vi. Mt k
thut khc c tn gi nhum acid-fast phi c s dng pht hin cc loi vi khun ny.
Trong chng ny, chng ta s tho lun v vi khun Mycobacterium tuberculosis, vi khun gy
bnh lao; Mycobacterium avium complex (MAC), vi khun thng gy cc th bnh lan ta bnh
nhn mc AIDS; v Mycobacterium leprae, vi khun cn nguyn ca bnh phong. Mc d cu trc
mng t bo c o vi hm lng lipid cao cho php cc vi khun ny gy ra nhng bnh tt
nghim trng, chng cng l gt chn Achilles ca nhm vi khun ny khi mt s khng sinh nh
isoniazid hay pyrazinamide c th tn cng vo cc phn t ny. V vy, cc thuc ny c tnh c
hiu ch ring vi cc loi vi khun Mycobacteria. Mt s loi thuc khc iu tr nhim khun
Mycobacteria, nh rifampin hay streptomycin, c c ch khng khun chung hn v cng c th
s dng iu tr cc bnh nhim khun gy ra bi cc loi vi khun khc.
Mycobacterium tuberculosis
Mycobacterium tuberculosis l vi khun cn nguyn gy bnh lao, l bnh truyn nhim
gy ra ch bi mt loi vi khun nhng gy t vong th hai ch sau bnh AIDS trn ton th gii.
Vic ht phi vi khun ny c th gy bnh tim n trong c th, v thng bnh nhn s mc th
bnh lao tim n, trong ngi bnh s khng c bt c triu chng no nhng vn mang vi
khun Mycobacteria trong c th. th nhim tim n, vi khun c th ph v c h thng bo
v ca vt ch v dn n s kch hot bnh. Thi im pht bnh ph bin nht l sau hai nm k
t khi b nhim khun hoc khi h min dch ca vt ch b suy yu do tui cao hoc do cc
nguyn nhn gy c ch min dch khc. Bnh lao khi c kch hot ch yu nh hng n
phi, tuy nhin chng c th nh hng n gn nh l tt c cc c quan khc trong c th (Hnh
15-1). bnh lao phi, nh phi thng b nh hng, v s to thnh cc hang lao l rt ph
bin. Cc bnh lao ngoi phi c th nh hng n cc hch bch huyt, mng phi, xng, h
sinh dc - tit niu, v h thn kinh trung ng. Bnh lao lan ta, hay cn c bit ti vi tn
bnh lao qun i (miliary tuberculosis) cng c th xut hin. Bt k xut hin b phn
143
no, bnh lao thng l bnh mn tnh, lm suy nhc c th, v c lin quan n s to thnh
cc u ht hoi t (nang lao).
Mycoplasma tuberculosis c pht trin cc c ch khng vi cc thuc khng khun. Do ,

cc liu php iu tr thng s dng nhiu loi thuc khng sinh khc nhau.
Tr liu khi u thng bao gm isoniazid, rifampin, pyrazinamide, v ethambutol (bng 15-
1). Vic s dng c bn loi thuc ko di trong vng hai thng, sau tr liu c thu hp li
vi vic ch s dng isoniazid v rifampin, nu chng vi khun vn cn nhy cm vi cc loi
thuc ny. Vic s dng isoniazide v rifampin c tip tc 4 thng hon thnh t tr liu.
Rifepentine thng c s dng thay th cho ripamficin trong pha iu tr lin tc ca tr liu
cho bnh nhn suy gim min dch bi v loi thuc ny c s dng mt tun mi ln thay v s
dng hng ngy. Rifabutin thng c thay th cho rifampin nhng bnh nhn ang c iu
tr HIV bi loi thuc ny s t tng tc vi cc qu trnh chuyn ha ca cc loi thuc khng
retrovirus (antiviral drugs).
Nu chng vi khun lao khng vi isoniazid v rifampin, bnh nhn s b mc phi lao
a khng thuc (multidrug-resistant tuberculosis). Vic iu tr lao khng thuc thng rt kh
khn v i hi vic s dng mt s loi thuc d phng thay th nh streptomycin, amikacin,
cycloserine, ethionamide, capreomycin, p-aminosalicylic acid, hay quinolone. Nhng thuc khng
khun ny thng t hiu qu hn cc tr liu c u tin v vic s dng chng c lin quan n
vic tng tn sut xut hin cc phn ng c hi. Cc khuyn co hin ti cho vic iu tr lao a
khng thuc thng khuyn vic thc thi tr liu vi t nht ba loi thuc khng sinh cha tng s
dng cho ngi bnh v cc loi khng sinh ny nhy cm vi chng Mycobacteria gy bnh
mi trng in vitro. Tr liu ny phi c ko di t nht l trong 18 ngy lin tc.
Vi nhng ngi bnh mc phi dng nhim lao m (tri vi th lao hot ng) c ti
lng vi khun thp hn, v kh nng xut hin cc t bin t nhin dn n s khng khng
sinh l thp hn rt nhiu. Do , ngi bnh vi th lao ny c th c cha tr vi n tr liu,

thng thng l isoniazid trong vng 9 thng. Ngi bnh nghi ng mc phi cc th bnh tim n
gy ra bi cc chng khun lao khng isoniazid c th c iu tr vi rifampin trong vng 4
thng.
Bng 15 -1 : Cc loi thuc khng khun c s dng trong vic iu tr nhim
Mycobacterium tuberculosis
Th bnh hot ng
(Isoniazid + rifampin + pyrazinamide + ethambutol) x 2 thng, sau (isoniazid + rifampin)

x 4 thng
Th bnh m
Isoniazid x 9 thng
LCH S
Lao l mt bnh tt rt lu i. Phn ng khuch i chui gene bng polymerase trn cc mu m
t cc xc p xc nhn s tn ti ca bnh lao Ai Cp c i v chu M thi k trc
Columbus khm ph chu M.
Mackowiak PA, Blos VT, Aguilar M, et al. On the origin of American tuberculosis. Clin Infect
Dis. 2005;41:515518.Zink AR, Sola C, Reischl U, et al. Characterization of Mycobacterium
tuberculosis complex DNAs from Egyptian mummies by spoligotyping. J Clin Microbiol.
2003;41:359367.
CU HI N TP:
Bi v vi khun Mycobacterium tuberculosis c th pht trin cc c ch khng cc loi thuc
khng sinh, hu ht cc tr liu u tin cho th lao hot ng thng bao gm ________
Liu php khng sinh ph bin nht dng iu tr th lao hot ng bao gm _________,
_________, _________, v _________.
Cc khng sinh d phng thay th cho vic cha tr lao bao gm _________, _________,
_________, _________, _________, _________, v _________.
Bnh nhn mc phi bnh lao tim n thng ch cn c iu tr vi mt mnh _________.
TI LIU C THM:
Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease
Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J
Respir Crit Care Med. 2003;167:603662.
Di Perri G, Bonora S. Which agents should we use for the treatment of multidrug-resistant
Mycobacterium tuberculosis? J Antimicrob Chemother. 2004;54:593602.
Espinal MA, Laszlo A, Simonsen L, et al. Global trends in resistance to antituberculosis drugs.
World Health Organization-International Union against Tuberculosis and Lung Disease Working
Group on Anti-Tuberculosis Drug Resistance Surveillance. N Engl J Med. 2001;344:12941303.
145
Jasmer RM, Nahid P, Hopewell PC. Clinical practice. Latent tuberculosis infection. N Engl J Med.
2002;347:18601866
CHNG
Chng 16. Vim Phi

SVD4. Nguyn Phi Ton, H Dc HN
Hiu nh: DS. V Th H
Trong cuc chin gia cc vi khun v c th ngi, phi l mt chin trng ph

bin. Vi khun xm nhp thng xuyn t vng hu hng v mi hng c to
iu kin bi cc ng dn thng, ngn, thng thong ca kh qun v ph qun. May
mn thay, nhiu vi khun xm nhp thnh cng vo phi li b tiu dit mt cch
nhanh chng v thm lng. Tuy nhin, v tt c qu thng xuyn, cc c ch bo v
ng h hp b qu ti, v cc du hiu ca vim phi tr nn r rng. Bnh nhn
b st, n lnh, rt run, ho, vim mng phi, v, i khi, kh th. Thm khm lm
sng thy nhp tim nhanh, th nhanh, v nghe c bt thng trn ngc. Bt
thng trong xt nghim bao gm s lng bch cu mu ngoi vi cao, thng l
bch cu trung tnh. X-quang phi cho thy phi b thm nhim.
Vim phi xy ra hai hnh thc chnh: vim phi mc phi cng ng (CAP)
v vim phi mc phi bnh vin (HAP). ng nh theo tn gi, hai loi
vim phi ny c nh ngha bi ni nhim tc nhn gy bnh. Trong khi,
CAP thng xy ra nhng ngi c tr trong nh ca h, HAP lm nng
thm vi nhng ngi ang trong bnh vin. Tm quan trng ca s khc
bit ny l cc trng hp m vim phi mc cho thy mt phm vi ln cc
loi mm bnh c th gy ra n v, do , vic iu tr theo kinh nghim l
thch hp nht. Lu rng mt s lng ngy cng ln ca cc bnh nhn nm
ngoi hai loi ny; h c tr ti nh dng lo hoc cc c s chm sc di
hn, hoc l h thng xuyn tip xc vi nhn vin y t hoc cc thit b y t
nh ti cc trung tm lc mu. Khi nhng c nhn ny b vim phi, h s
c phn loi l vim phi lin quan chm sc y t (health careassociated
pneumonia - HCAP) v cn c x tr tng t vi nhng ngi c HAP.
VIM PHI MC PHI TI CNG NG

CAP cp tnh c chia thnh hai loi: in hnh v khng in hnh. Mc d
cch phn loi rt hu ch trong vic tm hiu nguyn nhn ca vim phi, vn c
nhng phn cha c hiu, v cc biu hin lm sng ca vim phi in hnh v
vim phi khng in hnh khng khc bit c th hu ch trong cc quyt
nh v iu tr.
Vim phi in hnh thng c xut hin t ngt nhng cn st, rt run, au ton
b ngc, v ho nhiu. Hay gp bnh nhn hn 50 tui. X-quang cho thy hnh nh
147
thm nhin thy phi v phn on. Nguyn nhn c nghi ngh trong CAP in
hnh thng l Streptococcus pneumoniae and Haemophilus inuenzae (Bng16-1).
Nhng vi khun hiu kh gram dng v Staphylococcus aureus th t gp hn.
Bng 16-1 Vi khun gy CAP
Tn vi khun T l
Streptococcus pneumoniae 42%
Mycoplasma pneumoniae 19%
Chlamydophila pneumoniae 10%
Haemophilus inuenzae
Gram dng hiu kh khc 7%
9%
Legionella spp. 4%
Ngc li, CAP khng in hnh thng xy ra sau mt ln mc nhng bnh h hp

nh nh vim hng v s mi. Mc vim phi thng nh v khng gy ho
nhiu. Bnh nhn c tui thp hn so vi ngi mc CAP in hnh, v X-quang c
th thyhnh nh thm nhim khe k thay v hnh nh thm nhim thy hoc khc
on. Legionella spp., Mycoplasma pneumoniae, v Chlamydophila pneumoniae l
nhng vi khun thng gy ra vim phi khng in hnh (Bng 16.1). Nhim virus
nh virus cm cng l mt trong nhng nguyn nhn dn n vim phi khng in
hnh.
iu tr CAP theo kinh nghim mt cch ti u cn nhiu tranh ci nhng hu ht cc ca

u phi da trn vi khun gy bnh ph bin nht, yu t c nhn dn n, v mc
nng ca bnh. (Hnh 16-1 v Bng 16-2).
Bng 16-2 iu tr khng sinh theo kinh nghim cho CAP
Nhm khng sinh Tn khng sinh

Trng hp nh (iu tr ngoi tr)
Khe mnh trc (khng c yu t nguy c khng penicillin Streptococcus
Macrolide ng ung
pneumoniae) Azithromycin, clarithromycin, erythromycin
hoc
Tetracycline ng ung Doxycycline
C yu t nguy c Streptococcus pneumoniae khng penicillin
Quinolone ng ung Moxioxacin, levooxacin, gemioxacin
hoc
Betalactam ng ung liu cao Amoxicillin, amoxicillin/clavulanate,
cefuroxime
phi hp
Macrolide ng ung Azithromycin, clarithromycin, erythromycin
Trng hp trung bnh (bnh nhn di s gim st ca nhn vin y t)
Quinolone Moxioxacin, levooxacin
hoc
Macrolide Azithromycin, clarithromycin, erythromycin
phi hp
Betalactam Cefotaxime, ceftriaxone, liu cao ampicillin
Trng hp nng (bnh nhn trong khoa hi sc tch cc)
Betalactam Cefotaxime, ceftriaxone, liu cao
ampicillin/sulbactam
phi hp vi
Macrolide Azithromycin
hoc
Quinolone khng t cu Moxioxacin, levooxacin
Nu n gh i n gh c Pseudomonas aeruginosa, phi hp thm:
2 ch phm khng Pseudomonas aeruginosa
Nu nghi ngh c methicillin-resistant Staphylococcus aureus ( M R S A ) , phi hp thm:
Glycopeptide Vancomycin
hoc
Linezolid
Vi nhng bnh nhn nh c th iu tr ngoi tr, cc chuyn gia khuyn
co s dng mt loi marcrolide ng ung (azithromycin,
clarithromycin, erythromycin) hoc doxycycline tr khi bnh nhn c cc
bnh i km hoc l nu khng c nguy c nhim vi S. pneumoniae khng
penicillin. Trong trng hp ny, vic iu tr nn c vi (1) mt
149
quinolone khng t cu ng ung (moxioxacin, levooxacin,
gemifloxacin)
hoc mt ch phm betalactam ng ung (amoxicillin, amoxicillin/clavulanate,
cefuroxime) liu cao v mt macrolide (azithromycin, clarithromycin,
erythromycin). Cc macrolide v doxycycline c hiu qu tt vi nhng nguyn nhn
gy vim phi khng in hnh, H. inuenzae, v mt vi chng S. pneumoniae. Ngc
li, cc beta-lactam c hiu qu tt trn S. pneumoniae. Khi dng vi liu cao beta-lactam
c th dit c hu ht cc chng S. pneumoniae tr nhng chng khng thuc mnh.
Amoxicillin/clavulanate v cefuroxime cng c tc dng rt tt trn H. inuenzae. Vi
s b sung ph tc dng cho nhau, cc chuyn gia cm thy rng cn phi phi hp cc
loi khng sinh ny s dng cng nhau iu tr CAP nhng bnh nhn c nguy c
khng penicillin S. pneumoniae. Quinolone khng t cu ng ung c hiu qu cao trn
MRSA, H. influenzae, v cc mm bnh khng in hnh v cng iu tr CAP trong
iu tr ngoi tr nu c nghi ngh n t cu khng penicillin S. pneumoniae. R rng,
quinolone v doxycycline nn trnh tr nh.
Vi nhng trng hp c mc trung bnh cn nhp vin, ng tim tnh mch thng
c s dng. Bnh nhn c iu tr hoc (1) mt liu php phi hp ca mt
macrolide (azithromycin, clarithromycin, erythromycin) v mt betalactam
(cefotaxime, ceftriaxone, liu cao ampicillin) hoc (2) n tr liu bng mt quinolone
khng t cu (moxifloxacin, levofloxacin). C hai liu php ny u c hiu qu trn S.
pneumoniae (bao gm c chng khng penicillin), H. influenzae, Legionella spp., v mt
s nguyn nhn khng in hnh khc.
Bnh nhn vi CAP nng cn phi nhp vin khoa hi sc tch cc s c iu tr bng
mt betalactam (cefotaxime, ceftriaxone, ampicillin / sulbactam) cng vi hoc
azithromycin hoc mt quinolone khng t cu (moxifloxacin, levofloxacin). Nu cc
yu t nguy c nhim Pseudomonas aeruginosa c xut hin (v d, tin s gin ph
qun, s dng steroid, hoc iu tr khng sinh ph rng), phc nn bao gm hai
ch phm khng Pseudomonas aeruginosa. Tng t nh vy, nu cc yu t nguy c
mc CAP do MRSA, c mt, cn thm vo phc mt ch phm khng t cu thch hp
(vancomycin, linezolid).
VIM PHI MC PHI BNH VIN
HAP c chia thnh khi pht sm (xy ra trong vng 5 ngy u tin sau nhp vin)
v khi pht mun (xy ra sau 5 ngy nhp vin). HAP khi pht sm thng ging
CAP c im nguyn nhn gy bnh mc phi cng ng. Nhng tc nhn gy
bnh l vi khun Streptococcus pneumoniae, H. influenzae, MRSA, v nhng vi khun
gram m ng rut cn nhy vi khng sinh (Bng 16-3). Ngc li, HAP khi pht
mun l do mc phi vi khun bnh vin, nh P. aeruginosa, Acinetobacter spp., trc
khun gram m ng rut khng khng sinh, v MRSA. Trong mt s bnh vin,
Legionella pneumophila cng l nguyn nhn chnh gy bnh. Vi khun mc phi
151
bnh vin thng khng vi nhiu khng sinh v iu ny cng th hin nhng kt
qu lm sng xu nhng bnh nhn mc HAP. V nhng l do trn, cc phng php
iu tr ca HAP khi pht sm v khi pht mun khc nhau.
Ngoi l v s khc bit gia HAP khi pht sm v khi pht mun l nhng bnh
nhn c khi pht sm HAP (hoc CAP) nhng c nhp vin gn y (trong
vng 3 thng), ngi c tr trong mt nh dng lo hoc mt c s chm sc di hn
, hoc nhng ngi c tip xc vi mi trng y t hoc nhng ngi c iu tr
khng sinh ko di. Nhng c nhn ny c th b HCAP v thng b nhim vi khun
khng khng sinh v phi c iu tr nh trng hp HAP khi pht mun.
Table 16- Bacterial Causes of Hospital-Acquired Pneumonia

3 (HAP)
Bacteria
Incidence
Early-onset HAP (without risk factors for multidrug-resistant
organisms)
Methicillin-sensitive Staphylococcus aureus 29%
Haemophilus inuenzae
35% 23%
33%
Enterobacteriaceae 5%
25%
Streptococcus pneumoniae 7%
23%
Late-onset HAP (or HAP with risk factors for multidrug-
resistant
Pseudomonasorganisms)
aeruginosa 39%
64%
Acinetobacter spp. 6%
26%
Enterobacteriaceae 16%
31%
Methicillin-resistant Staphylococcus aureus 0%
20%
S la chn iu tr theo kinh nghim ban u cho HAP l c bit quan
trng bi v nhng phc iu tr khng thch hp (v d, thuc khng
sinh khng c hiu qu chng li cc vi khun gy bnh) c lin quan vi t
l t vong tng ln, ngay c khi sau c iu chnh li sau khi c d liu
nui cy vi sinh. R rng, mt yu t nguy c i vi iu tr khng sinh
khng thch hp l nhim mt vi sinh vt a khng do cc vi sinh vt ny c
nhiu kh nng khng vi phc iu tr theo kinh nghim.
Bi v cc vi khun gy HAP khi pht sm cng tng t nh nhng

vi khun gy ra CAP (Bng 16-3), cc liu php iu tr khng sinh cho
hai hi chng ny l tng t. iu tr khng sinh theo kinh nghim cho
HAP khi pht sm (khng c yu t nguy c nhim vi sinh vt a khng)
gm ceftriaxone, quinolone (levofloxacin, moxifloxacin, ciprofloxacin),
ampicillin / sulbactam, hoc ertapenem (Bng 16-4 v Hnh. 16-2). iu
tr HAP khi pht mun hoc vim phi bnh nhn c cc yu t nguy
c nhim vi sinh vt a khng l phc tp hn. ti a ha kh nng cho
t nht mt thuc c hiu qu chng li cc vi khun khng thuc cao m
gy ra loi bnh vim phi, kt hp iu tr bng thuc khng sinh t t
nht hai loi khng sinh khc nhau c khuyn khch. Ngoi ra, nhng
thuc ny nn c ph gm P. aeruginosa, mt trong nhng nguyn nhn
ph bin nht ca HAP khi pht mun. Phc hu ch bao gm
cephalosporin khng P. aeruginosa (ceftazidime, cefepime), carbapenem
(imipenem, meropenem) hoc piperacillin / tazobactam kt hp mt vi
quinolone (ciprofloxacin, levofloxacin), hoc aminoglycoside
(gentamicin, tobramycin, amikacin) (Bng 16-4 v Hnh 16-3).
nhng bnh nhn c nghi ng nhim MRSA, linezolid hoc vancomycin nn c

thm vo. Nhng bnh nhn ny c th nhim cu khun gram dng v nn nui cy
bnh phm dch kh qun hoc l nhng bnh nhn ang trong khoa hi sc tch cc vi
t l cao nhim MRSA.
Mt s vn cn c lu khi la chn khng sinh t danh sch ny cho bnh nhn.

u tin, tt nht khng s dng cc thuc m bnh nhn c s dng gn y bi v
lm tng nguy c khng thuc. Th hai, d liu khng thuc a phng nn c s
dng hng dn vic la chn mt thuc. Cui cng, thuc khng sinh nn c la
chn gim thiu nguy c phn ng c hi ca thuc. V d, nu c th, vic s dng
ko di ca aminoglycosides cn trnh bnh nhn ln tui v nhng ngi c bnh thn
mn v nguy c nhim c thn.
153
Bng 16- iu tr khng sinh theo kinh nghim cho HAP
4
HAP khi pht sm (khng c yu t nguy c nhim vi khun a
Cephalosporin
khng) Ceftriaxone
Hoc
Quinolone Levooxacin, moxioxacin, ciprooxacin
Hoc
Aminopenicillin/ betalactamase Ampicillin/sulbactam
Hoc
Carbapenem Ertapenem
HAP khi pht mun (or HAP c yu t nguy c nhim vi khun
a khng)
Cephalosporin khng pseudomonas Ceftazidime, cefepime
Hoc
Carbapenem Imipenem, meropenem
Hoc
Penicillin ph rng/Khng betalactamase Piperacillin/tazobactam
Phi hp
Quinolone Ciprooxacin, levooxacin
Hoc
Nu nghi ng nhim MRSA, thm vo:
Hoc
Linezolid
155
Cu hi
1. Vi khun gy vim phi mc phi cng ng khng in hnh bao gm
, , v .
2 . Ba nhm thuc c s dng ph bin nht iu tr CAP l
, , v .
3. iu tr theo kinh nghim cho CAP nng l cng vi

hoc mt .
3. V i khun gy HAP c th c chia thnh 2 nhm: (a) vi khun gy HAP
and (b) vi khun gy HAP hoc HAP
vi bnh nhn c nguy c nhim vi sinh vt a khng thuc.
5. iu tr cho bnh nhn HAP khi pht sm (khng c yu t nguy c nhim vi

khun a khng) l : , ,
, hoc
.
6. iu tr HAP bnh nhn c nguy c nhim vi sinh vt a khng thuc bao
gm 1 thuc t 2 nhm sau: (group 1) mt thuc khng pseudomonas
, mt vi ph cha Pseudomonas, hoc
; cng vi (nhm 2) mt hoc mt
. Nu nghi ng nhim MRSA, hoc
nn c thm vo.
C THM
Chastre J, Fagon JY. Ventilator-associated pneumonia. Am J Respir Crit
Care Med. 2002;165:
867903.
Halm EA, Teirstein AS. Clinical practice. Management of community-
acquired pneumonia. N Engl
J Med. 2002;347:20392045.
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society
of America/American Thoracic Society consensus guidelines on the
management of community-acquired pneumonia. Clin Infect Dis.
2007;44(suppl 2):S27S72.
Niederman MS, Craven DE, Bonten MJ, et al. Guidelines for the
management of adults with hospital-acquired, ventilator-associated, and
healthcare-associated pneumonia. Am J Respir Crit Care Med.
2005;171:388416.
Waterer GW, Rello J, Wunderink RG. Management of community-acquired
pneumonia in adults.
Am J Respir Crit Care Med. 2011;183:157164.
Chng 17 Nhim trng ng tit niu
Ngi dch: SVD5. L Th Tho, i Hc Y Dc Tp. HCM.
Ngi hiu nh: DS. V Th H
H thng tit niu l mt ca ngngn gia mi trng bn ngoi v bn trong ca c th v cc vi

khun gy bnh thng li dng ca ng ny gy nhim trng. C th con ngi khng c
bo v ca ng ny minh chng bi t l mc cc bnh nhim khun tit niu (NKTN) c tnh
khong 10% ph n mi nm. Cc bnh nhim trng c th tng i lnh tnh, ch lin quan n
nhim trng niu o v bng quang, trong trng hp ny c gi l vim bng quang cp tnh.
Ngoi ra, bnh c th nng hn v lin quan n thn trong cc trng hp vim b thn. Cc c
nhn b vim bng quang cp do vi khun thng c cc triu chng kh tiu, tiu lt nht v
tiu mu. Cc triu chng khc nh st, n lnh, bun nn, nn, v au mn sn gi vim
b thn. Xt nghim cho thy c m, mu v vi khun trong nc tiu.
Nhim khun ng tit niu NKTNc phn loi thnh NKTN khng bin chng v NKTN
bin chng . NKTN khng bin chng thng NKTN xy ra ngi tr, khe mnh, ph n
khng mang thai; NKTN bin chng gm tt c cc NKTN khc. NKTN bin chng in hnh l
mt nhim trng mt ngi ph n mc bnh tiu ng hoc c mt cu trc bt thng ca
h thng tit niu hoc NKTN mc phi trong bnh vin. Vic phn bit NKTN bin chng v
NKTN khng bin chng l rt quan trng v n nh hng n ph ca cc vi khun lin quan v
thi gian iu tr khng sinh.
Trong vim b thn v vim bng quang cp tnh khng bin chng, vi khun gy bnh c th d
on trc. Trong hu ht cc trng hp, Escherichia coli s c coi l cc sinh vt gy bnh
(Bng 17-1 v Hnh 17-1 v 17-2). Staphylococcus saprophyticus, Proteus mirabilis, Klebsiella
spp., v cc vi khun khc h Enterobacteriaceae khc i khi cng c pht hin khi nui cy.
Khng ging nh cc vi khun mc phi bnh vin, cc vi khun mc phi cng ng thng
nhy cm vi hu ht cc khng sinh. Trong NKTN c bin chng, vi khun thng l cc vi
khun khng khng sinh nh Pseudomonas aeruginosa, Enterobacter spp., Serratia spp.,
Citrobacter spp., v Staphylococcus aureus, hoc vi khun c kh nng khng cao hn nh cu
khun rut enterococci (Bng 17-1 v Hnh 17-3).
Khuyn co iu tr kinh nghim vim bng quang cp tnh khng bin chng l mt phc
vi 5 ngy nitrofurantoin (Bng 17-2). Phc iu tr 3 ngy vi trimethoprim-
sulfamethoxazol ng ung l la chn iu tr trc y, nhng v gia tng s khng, hin
nay ch c khuyn co nu t l khng ca tc nhn gy bnh ng tiu ti a phng
khng vt qu 20% v phc ny khng c s dng iu tr BN c tin s nhim
trng tiu 3 thng trc. C nitrofurantoin v trimethoprim-sulfamethoxazole u c hiu qu
chng li vi khun E. coli, cc vi khun h Enterobacteriaceae khc, v cc chng S. saprophyticus
gy ra cc bnh nhim trng.
Cng loi vi khun gy vim bng quang khng bin chng cng c th gy vim b thn khng
bin chng (Hnh 17-2). Cc khuyn co iu tr, tuy nhin c s khc nhau v nitrofurantoin
157
khng t c nng cao cn thit iu tr nhim khun huyt lin quan n vim b thn v
v hu qu nghim trng ca vic iu tr khng ph hp do cc vi khun khng mnh hn vi
trimethoprim-sulfamethoxazol khi vim b thn. Phc iu tr khuyn co ph thuc vo mc
nghim trng ca bnh, vi thuc ung c s dng cho bnh nh v truyn tnh mch cho
bnh nng (Bng 17-2). i vi bnh nh, quinolon ung (ciprofloxacin, levofloxacin) thng
c s dng theo kinh nghim. Phc iu tr bnh vim b thn nng: quinolon tim
(ciprofloxacin, levofloxacin); aminoglycoside (gentamycin, tobramycin, amikacin), c hoc
khng phi hp vi ampicillin; penicilin ph rng (piperacillin, ticarcillin), c hoc khng phi
hp vi mt thuc aminoglycosid; cephalosporin th h th ba (ceftriaxone, cefotaxime), c hoc
khng phi hp vi mt thuc aminoglycosid; carbapenem (imipenem, meropenem, doripenem,
ertapenem). iu tr thuc khng sinh i vi vim b thn nn c lin tip trong 7-14 ngy.
Lu rng moxifloxacin khng c chp thun cho s dng trong iu tr NKTN.
iu tr khng sinh i vi NKTN c bin chng phi c hiu qu chng li cc vi khun khng
i khi gy ra cc bnh nhim trng (Hnh 17-3 v Bng 17-2). Phc in hnh bao gm mt
quinolon (ciprofloxacin, levofloxacin), cefepim, carbapenem (imipenem, meropenem,
doripenem, ertapenem), hoc Penicillin ph rng/kt hp cht c ch beta-lactamase
(piperacillin/tazobactam, ticarcillin/clavulanat). Nu vi khun Gram dng c tm thy trn
vt nhum Gram ca nc tiu (gi s hin din ca vi khun cu khun rut enterococci),
ampicillin hoc amoxicillin cn c b sung. iu tr thng c duy tr trong 7-14 ngy hoc
lu hn.
Bng 17-1. Cc vi khun gy nhim trng ng tit niu
Vi khun T l mc
NKTN khng bin chng
Escherichia coli 53%79%
Proteus mirabilis 4%5%
Staphylococcus saprophyticus 3%
Klebsiella spp. 2%3%
Other Enterobacteriaceae 3%
NKTN bin chng
E. coli 26%29%
Enterococci 13%17%
Pseudomonas aeruginosa 9%16%
Klebsiella spp. 8%10%
Other Enterobacteriaceae 9%11%
Bng 17-2. Khng sinh iu tr NKTN theo kinh nghim
H khng sinh Khng sinh
Vim bng quang cp tnh khng bin chng
Nitrofurantoin
Trimethoprim-sulfamethoxazole
Vim b thn cp tnh khng bin chng
Quinolon Ciprofloxacin, levofloxacin

Aminoglycosides ampicillin Gentamicin, tobramycin, amikacin
Penicillin ph rng aminoglycoside Piperacillin
Cephalosporin th h 3 aminoglycoside Ceftriaxon, cefotaxim
Nhim trng ng tit niu c bin chng
Quinolon Ciprofloxacin, levofloxacin

Cephalosporin th h 4 Cefepim
Penicillin ph rng/ -lactamase Piperacillin/tazobactam,
ticarcillin/clavulanate
Nu vi khun gram dng c pht hin trong nc tiu, phi hp thm:
Aminopenicillin Ampicillin, amoxicillin
Hnh 17-1. Cc tc nhn s dng iu tr vim bng quang cp khng bin chng
Hnh 17-2. Cc tc nhn s dng iu tr vim b thn khng bin chng.
159
Hnh 17-3. Cc tc nhn c s dng iu tr nhim trng tiu bin chng.
Cu hi
1. Nguyn nhn ph bin nht ca vim bng quang cp tnh khng bin chng l
2. Khuyn co iu tr khng sinh theo kinh nghim i vi vim bng quang cp tnh mt ngi
ph n tr, khe mnh, khng mang thai l .. hoc
3. Nu vi khun Gram dng c pht hin trong nc tiu ca mt bnh nhn b nhim trng
ng tit niu c bin chng, ngi ta phi quan tm n .. nh cc sinh vt gy
bnh.
4. Bnh nhn b i tho ng, c cc bt thng v cu trc ca h thng tit niu, nhim vi
khun mc phi ti bnh vin, hoc nhng ngi c kh nng mc phi nhng vi khun ph rng,
c cho l nhim trng ng tit niu
5. Khng sinh iu tr NKTN c bin chng l .., ,
, hoc .
Chng 18. Bnh vim vng chu
Ngi dch: SVD5. L Th Tho, i Hc Y Dc Tp. HCM.
Ngi hiu nh: DS. V Th H
Bnh vim vng chu (VVC) l hu qu ng tic do cc hng ro lin tip bo v ca h thng
sinh dc n khng pht hin c s xm nhp ca cc vi khun ly truyn qua ng tnh dc.
Trong VVC, vi khun di chuyn t c t cung vo trong t cung v sau n ng dn trng,
bung trng, v khoang phc mc. Tnh trng vim dai dng c th dn n hnh thnh p xe v
so nhng t chc ny, dn n v sinh v mang thai ngoi t cung.
Cc bnh nhn mc VVC thng c biu hin chy mu bt thng, au khi giao hp, c dch
tit m o, au bng di, st v n lnh. Khm thc th thng ng ch l st, bt thng
c t cung hoc m m o, au v nhy cm t cung hoc phn ph ca t cung, v s chuyn
ng nhy cm ca c t cung. Xt nghim c th cho thy s lng t bo bch cu ngoi vi tng,
s hin din ca cc t bo bch cu trong dch tit m o, v tc mu lng v protein C phn
ng (CRP) tng.
C ch sinh bnh hc ca VVC lin quan n mt s tng tc phc tp gia cc vi khun ly

truyn qua ng tnh dc v h vi khun ch m o, c bit l vi khun k kh (Bng 18-1 v
Hnh 18-1). Nh vy, y l mt bnh nhim trng a khun. Cc vi khun ly truyn qua ng
tnh dc thng lin quan nht l Neisseria gonorrhoeae v Chlamydia trachomatis. Cc thnh
phn ca h khun ch m o thng c phn lp t cc tn thng VVC bao gm Bacteroides
k kh v Peptostreptococcus spp. cng nh vi khun k kh tu nh Escherichia coli,
Gardnerella vaginalis, Haemophilus influenzae, v lin cu streptococci nhm B. Hin nay, mc
v vai tr ca mi chng vi khun trn dn n s tin trin ca VVC vn cha r.
iu tr VVC theo kinh nghim phi da vo ph ca cc sinh vt c kh nng gy bnh ny cng

nh mc nghim trng ca bnh (Bng 18-2 v Hnh18-1). Tt c cc phc nn c hiu qu
chng li N. gonorrhoeae v C. trachomatis. Hin nay, vai tr ca vi khun k kh trong VVC cn
gy tranh ci, nhng mt s chuyn gia cm thy rng liu php iu tr cng cn chng li nhng
sinh vt ny. C nhn c mc bnh nh n trung bnh nn c iu tr ngoi tr vi khng
sinh ng ung. Phc khuyn co bao gm mt liu cephalosporin tim bp duy nht (v d,
ceftriaxon, cefoxitin + probenecid, cefotaxim) phi hp vi 14 ngy iu tr vi docyxyclin
ng ung, c hoc khng phi hp vi metronidazol. (Dng ng thi probenecid vi cefoxitin
lm chm s o thi ca cefoxitin, ko di nng tr liu.) Nhng ngi ang b bnh nng nn
c nhp vin v iu tr ban u vi cc thuc truyn tnh mch. Phc ban u thng gp
bao gm (1) mt cephalosporin c tc ng trn vi khun k kh (v d, cefotetan, cefoxitin) phi
hp vi doxycyclin hoc (2) clindamycin phi hp vi gentamicin. Phc th hai hiu qu hn
v gentamicin l hiu qu chng li vi khun gram m N. gonorrhoeae v clindamycin c tc ng
chng li C. trachomatis cng nh chng li nhiu vi khun k kh. Khng sinh tim tnh mch c
th c ngng 24 gi sau khi bnh nhn thy c ci thin lm sng, v hon thnh iu tr 14
ngy vi doxycyclin ung hoc clindamycin ung.
161
Bng 18-1. Mt s vi khun gy bnh vim vng chu
Vi khun T l mc
Neisseria gonorrhoeae 27%56%
Chlamydia trachomatis 22%31%
Vi khun k kh ty 20%78%
Hnh 18-1. Cc tc nhn c s dng iu tr bnh vim vng chu.

Bng 18-2. Phc iu tr bnh vim vng chu theo kinh nghim
Mc bnh nh ti trung bnh
Cephalosporin tim bp liu duy Ceftriaxon, cefoxitin + probenecid, cefotaxim
nht
+ doxycyclin ung
metronidazol ung
Mc bnh nng
Cephalosporin Cefotetan, cefoxitin
+ doxycycline
Hoc
Clindamycin
+ Aminoglycosid Gentamicin
Cu hi
1. Khng sinh iu tr bnh vim vng chu nn bao gm cc cht c hot tnh chng vi khun ly
truyn qua ng tnh dc nh . v . v c th l vi khun
2. Phc iu tr bnh vim vng chu mc nh l mt liu tim bp duy nht

phi hp vi ................................. c hoc khng phi hp ...
3. Hai phc iu tr bnh vim vng chu nng l (1) c tc ng chng vi
khun k kh phi hp vi v (2) . phi hp vi
4. Trong phc khng sinh bnh vim vng chu bao gm cefotetan cng vi doxycyclin,
cefotetan c hiu qu chng li cng nh trong khi
doxycyclin c hiu qu chng li
163
Chng 19: Vim mng no
L V K Nam-BV Nng
Kh nng gy bnh mnh m ca cc loi vi khun th hin r nht bnh l vim mng
no cp tnh. Bnh l ny thng tin trin rt nhanh v s dn n t vong nu khng c iu
tr bng liu php khng sinh. Mc d y hc hin i c nhng k thut chn on phc tp v
nhiu loi khng sinh c hiu lc cao, vn c xp x 1 trong 4 bnh nhn ngi ln b vim mng
no cp t vong. Hin nhin, c t bin sai s khi la chn khng sinh thch hp iu tr bnh
l ny.
Ngi bnh b vim mng no cp tnh gy ra bi vi khun thng c triu chng au
u, st, cng c, thay i trng thi tm thn, s nh sng, bun nn, nn ma v co git.
Thm khm thc th thng cho thy du hiu cng gy v i lc l suy gim chc nng thn
kinh. Mt trong nhng phng php chn on quan trng l vic xt nghim dch no ty. Dch
no ty ca ngi bnh vim mng no thng cho thy s tng s lng bch cu v nng
protein, nhng li suy gim nng glucose. Hn na, Phng php nhum Gram trn dch no
ty cng c th cho thy r hnh th vi khun gy bnh.
Cc vi khun gy bnh vim mng no thng c s khc nhau r rt theo tui (Bng
19-1). tr s sinh, Streptococcus agalactiae v Escherichia coli l cc vi khun chim u th.
Hin nay, vi vic s dng rng ri vaccine phng nga Haemophilus influenza type B th
Streptococcus pneumoniae v Neisseria meningitidis l cc loi vi khun ph bin phn lp c
bnh nhn tr nh. Neisseria meningitidis l cn nguyn ph bin gy bnh vim mng no
nhng tr em c tui ln hn v ngi mi ln, v Streptococcus pneumoniae l vi khun tm thy
nhiu nht bnh nhn ngi ln. mt thiu s bnh nhn c tui i rt nh hoc c tui cao,
v nhng bnh nhn b c ch min dch, Listeria monocytogenes thng c xc nh l cn
nguyn gy bnh vim mng no cp. Cc loi trc khun Gram m cng l loi vi khun cn
c quan tm nhng bnh nhn cao tui.
S hiu r c ch sinh bnh hc ca bnh l vim mng no cp tnh do vi khun c th
gip rt nhiu trong vic chn la cc tr liu thch hp. bnh l ny, vi khun thng phn
chia trong dch no ty, ni t c khng th v b th t h min dch. Do ni y thiu trm trng
cc phn ng phng th t h min dch ca c th, nn cc loi thuc khng sinh m ch c tc
dng c ch s pht trin ca vi khun (khng sinh km khun) l khng cho vic tr bnh dt
im. Cc loi khng sinh s dng phi c kh nng tiu dit vi khun (khng sinh dit khun)
trit tiu ton b vi khun trong dch no ty. Hn na, cc khng sinh ny phi thm nhp c
hng ro mu no vi mt lng t c nng cn thit dit khun. Do , rt nhiu
khng sinh c s dng vi liu cao hn khi iu tr bnh nhn vim mng no, so vi khi s
dng iu tr cc bnh l nhim khun khc. Cui cng, mt lng ln cc tn thng m c
lin quan n bnh l vim mng no do vi khun c cho l kt qu ca cc phn ng vim gy
ra bi mt s lng ln vi khun trong dch no ty v mng no; cc phn ng vim ny c th
tng ln bi hin tng v mng t bo ca vi khun t ngt khi vi khun tip xc ln u vi
thuc khng sinh dit khun. V l do ny, mt s chuyn gia khuyn co nn s dng km nhm
corticosteroid vi cc loi thuc khng sinh trong mt s tnh hung lm sng.
Bng 19-1 : Vi khun cn nguyn gy vim mng no
Tui Vi khun
Streptococcus agalactiae
0 3 thng Escherichia coli
Neisseria meningitidis
3 thng 18 tui Streptococcus pneumoniae
Haemophilus influenza
Streptococcus pneumoniae
18 50 tui
Neisseria meningiditis
> 50 tui Listeria monocytogenes
Trc khun Gram m
Nu khng c kt qu xt nghim nhum Gram ca dch no ty, liu php khng sinh cho
vim mng no cp do vi khun phi l liu php theo kinh nghim (Bng 19-2 v Hnh 19-1).
Cephalosporin th h III (cefotaxime, ceftriaxone) l xng sng ca hu ht mi tr liu khng
sinh theo kinh nghim bi v chng c tnh cht dit khun, c kh nng xm nhp vo dch no
ty kh tt, v hiu qu trong vic chng li hu ht cc chng khun S. pneumoniae, N.
menigitidis, v H. influenza. Tuy nhin, t l cc chng S. pneumoniae khng cephalosporin ang
tng ln nhiu ni trn th gii. Mc d cephalosporin c th t c nng cao phi v l
liu php khng sinh hiu qu trong vic iu tr vim phi gy ra bi hu ht cc chng vi khun
S. pneumoniae, ch tr cc chng vi khun khng thuc rt mnh. Tuy nhin, cc khng sinh ny
thng tht bi trong vic t c nng cn thit trong dch no ty tiu dit cc chng
khun khng thuc mc trung bnh. Do , cc khuyn co hin nay u khuyn tr liu
khng sinh kinh nghim cho vim mng no cp tnh do vi khun nn s dng km vancomycin
vi cephalosporin. Ampicillin nn c s dng cho tr nh di 3 thng hoc bnh nhn tui
i trn 50 c th m rng ph hot ng khng sinh sang vi khun Listeria monocytogenes v
Streptococcus agalactiae. (Cn lu rng L. monocytogenes l mt trong nhng vi khun Gram
dng him hoi m vic s dng vancomycin s khng c hiu qu - do , cn phi c thm
ampiciliin trong tr liu khng sinh) . nhng bnh nhn b c ch min dch sau khi c phu
thut thn kinh hoc nhng bnh nhn c t shunt dn lu dch no ty, hoc bnh nhn ang s
dng nhm steroid liu cao, iu tr khng sinh nn c m rng c th ph ph khng sinh
ln cc loi vi khun Staphylococcus spp. v trc khun Gram m khng thuc khng sinh.
165
Bng 19-2: Liu php khng sinh theo kinh nghim cho vim mng no cp tnh
(Khi khng c kt qu nhum Gram cho dch no ty c gi tr chn on)
Cephalosporin th h III Cefotaxime, ceftriaxone
cng vi
Vancomycin
Glycopeptide
Nu bnh nhn < 3 thng hoc > 50 tui

Thm Aminopenicillin Ampicillin
Nu bnh nhn suy gim min dch
cng vi
Ceftazidime
Cephalosporin
cng vi hoc khng Ampicillin
Aminopeniciillin
Hnh 19-1: Ph khng khun ca cc loi khng sinh ph bin c s dng iu tr vim
mng no cp tnh do vi khun
Vi tr c tui nh hn 3 thng tui, kt qu nhum Gram ca dch no ty thng

khng c gi tr chn on, v tt c cc bnh nhn nn c iu tr vi cephalosporin th h III
v vancomycin cho n khi nhn c kt qu nui cy vi sinh. Tuy nhin, bnh nhn ngi ln,
kt qu nhum Gram dch no ty nn c s dng trong vic chn la tr liu khng sinh ban
u cho bnh nhn vim mng no cp tnh do vi khun. Do cc khng sinh phi p ng yu cu
l c kh nng dit khun v c thm vo dch no ty cao, nn ch c mt s t cc khng sinh
l thch hp dng trong iu tr bnh vim mng no (Bng 19-3). Song cu Gram dng trn
hnh nh nhum Gram dng thng l chng c khng nh nhim khun S. pneumoniae, v
bnh nhn nn c iu tr vi cephalosporin th h III (cefotaxime, ceftriaxone) cng vi
vancomycin, c th chng li cc chng khun khng penicillin. Tuy nhin, hnh nh cu khun
Gram dng nhng mu bnh ca tr nh hn 3 thng tui thng l du hiu ca s nhim
khun S. agalactiae, v bnh nhn nn c iu tr vi ampicillin v gentamicin. Hnh nh song
cu gram m thng khng nh N. meningitidis l cn nguyn gy bnh, v bnh nhn nn c
iu tr vi Penicillin G hoc ampicillin. Hnh nh trc khun Gram m nh, a hnh thi thng
ph hp vi nhim khun H. influenza, v bnh nhn nn c iu tr vi cephalosporin th h III
(ceftriaxone, cefotaxime). Hnh nh trc khun Gram m kch thc ln hn, c bit tr nh,
thng khng nh s nhim khun E. coli, v bnh nhn phi c iu tr vi cephalosporin th
h III (cefotaxime, ceftriaxone). Hnh nh trc khun Gram dng cho thy L. monocytogenes l
vi khun gy bnh v bnh nhn cn c s dng penicillin G hoc ampicillin. Mt s chuyn gia
cn s dng thm gentamicin t c c ch dit khun cng hip lc. Nhng trong tt c mi
trng hp, liu php khng sinh phi c iu chnh ph hp khi nhn c kt qu xt nghim
nh gi nhy cm khng sinh vi vi khun.
Bng 19-3: Liu php khng sinh c hiu cho vim mng no cp tnh do vi khun
(Da vo kt qu nhum Gram ca dch no ty)
Cephalosporin th h III
Cefotaxime hoc ceftriaxone
cng vi
Neisseria meningitidis
Penicillin t nhin
Penicillin G
hoc
Aminopenicillin Ampicillin
Haemophilus influenza
Penicillin t nhin
hoc Penicillin G
Aminopenicillin
Ampicillin
cng vi hoc khng
Gentamicin
Aminoglycoside
Streptococcus agalactiae
Aminopenicillin
Ampicillin
cng vi
Aminoglycoside Gentamicin
167
Escherichia coli
CU HI N TP:
nhng bnh nhn ngi ln, vi khun gy bnh vim mng no cp tnh ph bin nht l
_______________, _______________, v _______________
Liu php khng sinh ph hp cho mt bnh nhn 65 tui b vim mng no cp tnh v cha c
c kt qu nhum Gram c ngha v mt lm sng l _______________ cng vi
_______________ cng vi _______________.
Liu php khng sinh thch hp dnh cho mt sinh vin 19 tui mc phi vim mng no cp tnh
v hnh nh nhum Gram cho kt qu song cu Gram m l _______________ hoc
_______________.
Liu php khng sinh thch hp dnh cho mt em b 2 thng tui m vic nui cy dch no ty
phn lp c Streptococcus agalactiae l _______________ cng vi _______________
TI LIU C THM:
Brouwer MC, McIntyre P, de Gans J, et al. Corticosteroids for acute bacterial meningitis.
Cochrane Database Syst Rev. 2010:CD004405.
Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment
of acute bacterial meningitis. Clin Microbiol Rev. 2010;23:467492.
Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial
meningitis. Clin Infect Dis. 2004;39:12671284.
van de Beek D, de Gans J, Tunkel AR, et al. Community-acquired bacterial meningitis in adults. N
Engl J Med. 2006;354:4453.
Chng 20. Vim m t bo
Dch: BS. L Th Lin
Hiu nh: DS. V Th H
Ging nh nhng lu i thi trung c c thit k bc tng thnh kin c trnh nhng k
tn cng, th c th chng ta cng c bao ph mt lp da bo v, c hiu qu khng ng trong
vic ngn chn vi khun c kh nng thm nhp lm tn thng lp m su. D l mi trng y
cc vi sinh vt nhng c th vn c gi an ton nh c hng ro ny, iu chng minh mc
nhim trng lin quan n nhng l hng trn da, nh l bng hay vt m.Vim m t bo l
mt trong nhng bnh l nhim khun thng xy ra khi vi khun xm nhp vo lp trung b v h
b.
Vim m t bo (VMTB) thng c st v nhng triu chng ti ch, nh l nhy cm, nng, ,
sng, da ph n cng, thng quanh vt thng hay vt try da c vai tr nh l ng xm nhp
vo c th. Trong mt vi trng hp, bnh c th tin trin nng n, v xut hin triu chng
nhim c ton thn gm mch nhanh, h huyt p.
Vi khun gy VMTB ph thuc vo v tr nhim trng v mt vi bt k phi nhim c bit vi

nguyn nhn gy bnh. V d, VMTB xy ra sau khi mt vt thng tip xc vi nc bin th gi
Vibrio vulnifcus l nguyn nhn. VMTB lin quan n vt lot chn trn bnh nhn i tho
ng th b gy ra bi vi khun gram dng hiu kh, vi khun gram m hiu kh v vi khun k
kh. Tuy nhin, hu ht VMTB bnh nhn c h min dch bnh thng th nguyn nhn n t
s xm nhp ca sinh vt trn da qua l hng hay gin on ca thng b. Do , VMTB khng
bin chng, c a bnh thng, khng c tip xc g khc thng trc th thng nguyn
nhn l Staphylococcus aureus, Streptococcus pyogenes hoc lin cu khc (Bng 20-1).
V kh c th xc nh vi khun c hiu gy bnh, nn iu tr thng da vo kinh nghim v

gm cc thuc c ph khng khun trn vi khun gram dng (Bng 20-2 v Hnh 20.1) . Tuy
nhin, Staphylococcus aureus v Streptococcus pyogenes ngy cng tng sc khng vi khng
sinh, iu ny lm phc tp la chn iu tr. Nhn chung, nhim trng nng nn c iu tr ni
tr bng khng sinh tim, tri li vi th nh v va th c th dng ng ung cho bnh ngoi
tr. nhng vng m t cu khng methicillin (MRSA) l ph bin hay khi c cc yu t thun
li khin MRSA hin din (nh l bnh nhn c tin s nhim MRSA, tng dng liu trnh
khng sinh gn y), cc la chn ng tim nn dng vo gm glycopeptide (vancomycin,
telavancin), linezolide, daptomycin, tigecyline v ceftaroline. Doxycycline, trimethoprime-
sulfamethazole, linezolide v clindamycin ng ung c th c s dng. Nu kh nng
nhim MRSA l thp, la chn thch hp cho ng tim gm peniciline khng t cu
(nafacilline, oxacillin), cephalosporin th h 1 (cefazoline) hoc clindamycin. Thuc ung gm
dicloxacillin, cephalosporin th h 1 dng ung (cephalexin, cefadroxil), clindamycin hoc
macrolide (azithromycine, clarithromycine, erythromycin). Trong mi trng hp, la chn
thc t nn da vo c im khng ti a phng.
169
Bng 20-1 Vi khun gy vim m t bo
Vi khun T l gy bnh
Staphylococcus aureus 13-37%
Streptococcus pyogenes 4-17%
Lin cu khc 1-8%
Bng 20-2 iu tr khng sinh theo kinh nghim trong vim m t bo

Nu nghi ng l t cu vng khng methicillin
Bnh nh n trung bnh (ng ung)
Tetracycline Doxycycline
Clindamycin
Sulfamid Trimethoprime-sulfamethoxazole
Linezolid
Bnh nng (ng tim)
Glycopeptide Vancomycine, televancin
Linezolide
Daptomycine
Tetracycline Tigecycline, doxycycline
Cephalosporin th h 5 Ceftaroline
Nu khng nghi ng l t cu vng khng methicillin
Bnh nh n trung bnh (ng ung)
Penicillin khng t cu Dicloxacillin
Cephalosporin th h 1 Cephalexin, cefadroxil
Clindamycin
Macrolide Azithromycin, clarithromycin, erythromycin.
Bnh nng (ng tim)
Penicillin khng t cu Nafcillin, oxacillin
Cephalosporin th h 1 Cefazolin
Clindamycin
Hnh 20-1. Hot tnh ca cc khng sinh dng iu tr vim m t bo
Cu hi:
1. Trn bnh nhn min dch bnh thng, khng c tip xc bt thng, nguyn nhn ph
bin nht gy VMTB l,., v . khc.
2. iu tr theo kinh nghim thch hp bng ng ung cho mt ngi th lp nh khe
mnh 48 tui, b bnh vim m t bo ti vt try trn cnh tay, tin trin khng nng n v
c nguy c MRSA thp s l., ., cephasporin th h ,
hoc.
3. bnh nhn nguy c MRSA thp, iu tr bng ng tim thch hp cho VMTB
l..,.,. hoc..
4. Mt ph n 72 tui cy vi khun pht hin nhim t cu khng methicillin MRSA , hin ti
huyt p thp v xut hin vim m t bo trn chn tri ti v tr m trc vi nm
ct b tnh mch hin th iu tr thch hp l., ..,
.., , hoc ..
171
Chng 21: Vim tai gia
Trong cc bnh tr em M, vim tai gia cp l bnh thng c k khng sinh. Sinh l bnh
ca nhim khun ny th hin s lin tc ca tai gia vi ng h hp trn thng qua ng Ot-tat
(Eustachian tube). in hnh nh, khi c bt k mt bt thng no ng h hp trn nh
nhim trng hay d ng gy sung huyt nim mc h hp v tt ngn ng Ot-tat. Kt qu l dch b
li ng tai gia, v b nhim trng do cc vi khun ng h hp trn xm nhp vo.
Tr em b vim tai gia cp tnh c th c cc biu hin nh au tai, nghe km, d cu knh, bing
n, th , st, sng ty xung quanh tai, chy dch nc tai, kim tra tai th thy c dch trong ng
tai gia v cc du hiu vim.
Bi v dch ca ng tai gia c to ra t cc vi khun ca ng h hp trn nn cc chng vi

khun ca thng gy vim tai gia bao gm Streptococcus pneumoniae, Haemophilus influenzae,
and Moraxella catarrhalis. Cc vi khun ny u c c ch khng penicillin, nh Streptococcus
pneumoniae thay i protein gn kt vi penicillin (PBPs), lm penicillin khng gn c vi vi
khun, c khong 1/3 n chng vi khun H.infuenzae, M. catarrhalis sn xut ra -lactamase,
men ly gii cc khng sinh -lactam. Do nhng iu ny phi c cn nhc n khi iu tr
vim tai gia cp.
Hin nay vn c nhiu tranh ci v vic c nn dng khng sinh cho tt c tr em b vim tai gia
cp tnh hay khng. Mt s chuyn gia cho rng i vi tr t 2 tui tr ln, khng c biu hin
bnh nghim trng th c th iu tr triu chng trong 48-72 gi, nu tnh trng c ci thin,
nhng tr ny c th khng cn phi s dng khng sinh. Nhng chuyn gia khc li cho rng tt
c tr em b vim tai gia nn c iu tr bng khng sinh, trong trng hp ny a s cc ch
nh l iu tr theo kinh nghim v vic nui cy vi khun t dch tai gia trong cc ca vim tai
cp khng phc tp t khi c thc hin.
Bng 1. Cc vi khun gy ra vim tai gia

Vi khun T l
Streptococcus Pneumoniae 25-50%
Haemophilus influenzae 15-30%
Moraxella catarrhalis 3-20%
Bng 2. iu tr khng sinh theo kinh nghim
iu tr u tay
aminopenicillin Amoxicillin liu cao
C yu t nguy c
khng amoxcillin Amoxicillin/ acid clavulanic
Aminopenicillin/ c ch -lactam
D ng nh vi penicillin
Cephalosporin dng ung Cefdinir, cefpodoxime, cefuroxime
D ng penicillin type 1
Macrolid Azithromycin, clarithromycin
Amoxicillin liu cao l la chn u tay trong iu tr vim tai gia cp tnh. Thot nhn, vic la
chn tc nhn ny ging nh khng ph hp vi tnh trng nhim khun thng c gy ra bi
cc vi khun khng penicillin. Tuy nhin khi c s dng liu cao, nng ca Amoxicillin
trong dch mng nhy tai gia vt ngng nng c ch ti thiu (MIC) ca tt c cc chng vi
khun tr chng S. pneumoniae khng cao. i vi bnh nhn c yu t nguy c nhim vi
khun khng amoxicillin nh tr va mi c iu tr bng -lactam, tr vim kt mc c m
do H. influenzae nn c iu tr vi amoxicillin/acid clavulanic. i vi tr d ng nh vi
penicillin (khng phi d ng type 1), c th chuyn sang s dng cephalosporin dng ung nh
cefdinir, cefpodoxime, cefuroxime. Trong trng hp, tr b d ng type 1 vi penicillin (phn ng
nga, phn ng qu mn), macrolid (azithromycin, clarithromycin) c khuyn co.
173
Chng 22: Vim ni tm mc nhim khun
SVY6. Hong Th Thu Trang, Hc vin Y Dc hc c truyn Vit Nam
Hiu nh: DS. V Th H
T lu tim c coi l c quan quan trng nht trong c th ngi. Ngn ng ca chng ta
khng thiu nhng thnh ng khun so minh ha cho nhn nh ny, nh tm s thn mt
(heart-to-heart talk), i thng vo trng tm vn (get to the heart of the matter). Nu tim chm
hot ng d ch trong giy lt cng c th gy nguy hi n tnh mng. V l do ny, cc vi
sinh vt tn cng vo tim s gy ra hu qu v cng nghim trng. Mt trong s l vim ni
tm mc nhim khun, mt nhim khun mng trong tim, c bit l cc van tim.
Bnh nguyn ca vim ni tm mc nhim khun kh r rng. in hnh, vi khun xm nhp vo

mu theo nhiu c ch, bao gm thng qua cc th thut nha khoa, qua t catherer tnh mch
hoc tim chch ma ty. Sau , vi khun s gn vo b mt van tim, thng l nhng vng ni
tm mc khng ton vn do bt thng dng mu chy qua. Nhng bt thng dng ny thng l
hu qu ca bt thng van tim gy ra bi thp tim hoc khuyt tt bm sinh. Nt si - to bi t
huyt, tiu cu v vi khun bm vo ni tm mc thng hnh thnh nhng v tr b nhim
khun v to nn mi trng c tr an ton vi khun tn ti v nhn ln. Hu qu l cc van tim
s dn dn b hy hoi.
Mc d c cng nhn l mt bnh thc th t nhng nm 1500, chn on vim ni tm mc

nhim khun ti nay vn gp nhiu kh khn. Bnh nhn than phin v mt mi, kh chu, suy
nhc, st, n lnh, m hi v m v kh th khi gng sc. Cc triu chng lm sng c th
khng r rng km theo st v tiu ra mu. Cc du hiu gi nhiu n vim ni tm mc nhim
khun nh cc nt Osler, tn thng Janeway, m Roth, v xut huyt mnh vn t gp hn.
Tuy nhin, mt gi r rng cho s hin din ca vim ni tm mc l ting thi tim l(new heart
murmur), nhng bc s lm sng cn trng s da vo y gi chn on. nh lng trong
phng xt nghim c th cho bit tc lng hng cu tng (ESR) v nng protein-C phn ng
tng (CRP), thiu mu nh, cng nh cc kt qu xt nghim nc tiu bt thng, i mu, i
m v protein niu.
Yu t bnh nguyn ch yu ca vim ni tm mc nhim khun c khc nhau i cht gia cc

nhm i tng dn c c nghin cu, tuy nhin, nhn chung lin cu nhm viridans (viridans
group streptococci), Staphylococcus aureus, v cu khun ng rut enterococci ch yu gy
bnh vim ni tm mc van tim t nhin. Trong khi , t cu khng sinh men coagulase
(coagulase-negative staphylococci - CNS) v t cu vng (Staphylococcus aureus) l nguyn
nhn chnh gy bnh vim ni tm mc vi van tim nhn to (Bng 22-1). Trong s lin cu
viridans, cc chng Streptococcus sanguinis, Streptococcus mutans, and Streptococcus mitis l
ph bin nht. Mt t l nh cc ca vim ni tm mc nhim khun c gy ra bi mt nhm trc
khun gram m vit tt l HACEK: Haemophilus parainfluenzae, Aggregatibacter aphrophilus,
Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, v
Kingella kingae.
Bng 22-1 Nguyn nhn gy vim ni tm mc nhim khun
Vi khun T l
Lin cu viridans 18% - 48%
Staphylococcus aureus 22% 32%
Enterococci 7% 11%
T cu khng sinh men coagulase 7% 11%
Nhm HACEK 2% 7%
HACEK gm Haemophilus parainfluenzae, Aggregatibacter aphrophilus,
Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella
corrodens, v Kingella kingae.
Mi trng bo v nhng nt si khin cc vi khun gy vim ni tm mch rt kh iu tr.

Khng sinh dit khun, ch khng phi km khun, c ch nh vi liu cao, s dng trong thi
gian di. Do nguyn nhn ch yu gy vim ni tm mc l trc khun gram dng nn nhm
-lactam thng c s dng phi hp vi gentamycin nhm tng hiu qu dit khun. D vy,
iu tr tch cc th khng phi lc no cng v can thip ngoi khoa thng c ch nh, nn
trong qun l bnh nhn vim ni tm mc nhim khun nn bao gm hi chn ngoi. Vi c
im iu tr vim ni tm mc nhim khun l kh khn, li phi ch nh khng sinh trong thi
gian di nn xc nh chng sinh vt gy bnh bng cy mu nhiu ln l vic lm quan trng
a ra liu php iu tr ti u.
Khng him trng hp bnh nhn vim ni tm mc nhim khun c kt qu cy mu m tnh do

dng khng sinh trc . Trong bnh cnh ny, vancomycin v gentamicin liu phi hp
hip ng c khuyn co s dng song hnh vi ciprofloxacin iu tr khng sinh theo kinh
nghim cho nhng bnh nhn vim ni tm mc trn van tim t nhin (Bng 22-1 v Hnh 22-1).
Vancomycin c hiu qu trong iu tr S. aureus v lin cu viridans ng thi cng l khng sinh
dit khun vi phn ln cc chng Enterococcus khi s dng phi hp cng gentamicin.
Ciprofloxacin c tc dng chng li cc vi khun HACEK. iu tr khng sinh theo kinh nghim
trn bnh nhn vim ni tm mc nhim khun thay van tim nhn to tng i phc tp,
thng bao gm vancomycin vi liu phi hp hip ng gentamicin v rifampin bao ph ti
u vi chng staphylococci. Rifampin c thm vo v n lm tng thi loi staphylococci khi
van tim nhn to. Mt s chuyn gia khuyn co s dng thm ciprofloxacin t c hiu qu
iu tr cao hn vi nhng vi khun khc, nh nhm HACEK.
Bng 22-2 S dng khng sinh theo kinh nghim trong iu

tr vim ni tm mc nhim khun
Trn van t nhin
Vancomycin
cng
Gentamicin
cng
175
Ciprofloxacin
Trn van nhn to
Vancomycin
cng
Gentamicin
cng
Rifampin hoc ciprofloxacin
Hnh 22-1 Hot ng ca cc khng sinh c s dng

trong iu tr vim ni tm mc nhim khun
L tng nht l cy mu s xc nh c loi vi khun gy bnh t ra hng iu tr tp

trung vi nguyn nhn gy vim ni tm mc nhim khun. Cc phc khng sinh iu tr gii
thiu y ph hp vi nhng kin thc bit v tnh nhy cm ca vi khun gy bnh, ng
thi cng chng minh tnh hiu qu qua nhiu th nghim lm sng.
iu tr vim ni tm mc nhim khun gy ra bi lin cu viridans trn bnh nhn van tim t
nhin ph thuc vo nhy cm ca dng vi khun vi nhm penicillin (Bng 22-3 v Hnh
22-1). Nhng chng nhy cm cao vi nhm penicillin (Nng c ch ti thiu [MIC] 0.12
g/mL) nn c iu tr bng penicillin G hoc ceftriaxone trong vng 4 tun. Liu trnh c th
rt ngn cn 2 tun nu phi hp gentamycin vi mt trong 2 loi thuc k trn do phi hp thuc
lm hip ng tc dng dit khun. Nn ch nh penicillin G hoc ceftriaxone cho nhng chng
lin cu viridans nhy cm trung bnh vi penicillin (MIC 0.12 g/mL v 0.5 g/mL) trong
vng 4 tun, phi hp cng gentamycin trong 2 tun u tin. Nhng chng khng cao vi
penicillin (MIC 0.5 g/mL) c th c iu tr bng penicillin G hoc ampicillin t 4 n 6
tun, phi hp cng gentamycin trong sut liu trnh. iu tr tn gc vi khun trn bnh nhn c
van nhn to kh hn trn van t nhin, bi vy vi nhng bnh nhn b vim ni tm mc nhim
khun thay van nhn to, penicillin G v ceftriaxone c ch nh ti 6 tun thay v 4 tun.
Gentamycin cng c k trong vng 6 tun, tr trng hp chng vi khun nhy cm hon ton
vi penicillin (MIC 0.12 g/mL). Khi , gentamycin c th c s dng trong vng 2 tun
hoc khng s dng gentamycin.
Bng 22 3 S dng khng sinh c hiu trong iu tr vim ni tm mc nhim
khun do lin cu viridans
Khng sinh Thi gian
Van t nhin
Nhng dng nhy cm cao vi penicillin (MIC 0.12 g/mL)
Penicillin G hoc ceftriaxone 4 tun
+ Gentamycin 2 tun
Nhng dng nhy cm trung bnh vi penicillin (MIC > 0.12 g/mL v 0.5 g/mL)
+ Gentamycin 2 tun
Nhng dng khng cao vi penicillin (MIC > 0.5 g/mL)
Penicillin G hoc ampicillin 4 6 tun
+ Gentamycin 4 6 tun
Van nhn to
Nhng dng nhy cm cao vi penicillin (MIC 0.12 g/mL)
Penicillin G hoc cefrtixone 6 tun
Gentamycin 2 tun
Nhng dng nhy cm trung bnh hoc khng cao vi penicillin (MIC > 012 g/mL)
+ Gentamycin 6 tun
Vim ni tm mc nhim khun do cc enterococcus nhy cm vi penicillin, trn bnh nhn van
t nhin/ van nhn c iu tr tng t nh vi cc lin cu viridian khng cao (Bng 22-4
v Hnh 22-1). Penicillin G hoc ampicillin c s dng cng vi gentamycin trong vng 4 n
6 tun. Gentamycin hip ng tc dng vi cc khng sinh khc ph v mng t bo cc vi khun
enterococcus v kt qu l khin vi khun b tiu dit. Nhng nhim khun gy ra bi cc
enterococcus khng penicillin c iu tr bng vancomycin phi hp gentamycin trong vng 6
tun. Vi nhng dng vi khun khng gentamycin nhng nhy cm vi streptomycin, c th
dng thuc sau thay th cho thuc u trong liu trnh iu tr. Vi cc trng hp vim ni tm
mc nhim khun gy ra bi nhng dng vi khun khng ton b aminoglycoside, hoc c
penicillin v vancomycin, vic iu tr vn cn nhiu tranh ci v nn tham vn chuyn gia.
Vim ni tm mc nhim khun do S. aureus gy ra trn bnh nhn van t nhin c iu tr
bng nafcilin hoc oxacillin trong vng 6 tun (Bng 22-5 v Hnh 22-1). C th s dng
gentamycin liu phi hp trong 3 n 5 ngy u tin; hip ng tc dng gia thuc ny vi
nhm penicillin c tc dng trn t cu lm tng o thi nhanh vi khun khi mu. Vi nhng
nhim khun do S. aureus khng methicillin (methicillin-resistant S. aureus - MRSA) gy ra,
vancomycin c s dng thay cho mt penicillin c tc dng tr t cu.
177
Bng 22-4 S dng khng sinh c hiu trong vim ni tm mc nhim khun do
Enterococci
Khng sinh Thi gian
Van t nhin
Nhng dng nhy cm vi penicillin v aminoglycoside
Penicillin G hoc ampicillin 4 6 tun
+ Gentamycin 4 6 tun
Nhng dng khng Penicillin v nhy cm vi aminoglycoside
Vancomycin 6 tun
+ Gentamycin 6 tun
Van nhn to
Nhng dng nhy cm vi c Penicillin v aminoglycoside
Penicillin G hoc ampicillin 6 tun
+ Gentamycin 6 tun
Nhng dng khng Penicillin v nhy cm vi aminoglycoside
Vancomycin 6 tun
+ Gentamycin 6 tun
Khi iu tr nhng nhim khun gy ra bi cc dng khng cao vi aminoglycoside nn
tham kho kin chuyn gia.
Staphylococci
Khng sinh Thi gian
Van t nhin
Nhng dng nhy cm vi Methicillin
Nafcillin hoc oxacillin 6 tun
Gentamycin 3 5 ngy
Nhng dng khng Methicillin
Vancomycin 6 tun
Van nhn to
Nhng dng nhy cm vi Methicillin
Nafcillin hoc oxacillin 6 tun
+ Rifampin 6 tun
+ Gentamycin 2 tun
Nhng dng khng Methicillin
Vancomycin 6 tun
+ Rifampin 6 tun
+ Gentamycin 2 tun
Vim ni tm mc trn van tim nhn to do S. aureus hoc Staphylococcus epidermidis gy ra,
phc iu tr bao gm nafcillin hoc oxacillin phi hp cng gentamycin v rifampin i vi
nhng dng vi khun nhy cm vi methicillin. Gentamycin phi hp lm tng kh nng dit
khun, rifampicin to iu kin thun li o thi cc t cu ny khi van nhn to. Vi nhng
nhim khun gy ra bi cc chng vi khun khng li nhm penicillin tr t cu, vancomycin l
la chn thay th cho nafcillin hay oxacillin. Nafcillin, oxacillin hoc vancomycin c duy tr
trong vng 6 tun hoc lu hn nu cn. Rifampicin c duy tr trong vng 6 tun v gentamycin
ch c s dng trong 2 tun u tin.
Vim ni tm mc nhim khun do nhm HACEK trn van t nhin hay van nhn to c iu
tr bng ceftriaxone hoc ampicillin-sulbactam hoc ciprofloxacin trong vng 4 n 6 tun
(Bng 22-6 v Hnh 22-1)
nhm HACEK
Khng sinh Thi gian
Van t nhin
Ceftriaxone 4 tun
Ampicillin-sulbactam 4 tun
Ciprofloxacin 4 tun
Van nhn to
Ceftriaxone 6 tun
Ampicillin-sulbactam 6 tun
Ciprofloxacin 6 tun
LCH S
D iu tr khng sinh ph hp, t l t vong lin quan n vin ni tm mc nhim khun vn
mc cao (20 n 25%). Tuy vy, y l mt bc tin ng k so vi thi k tin khng sinh,
khi m chn on vim ni tm mc nhim khun ng ngha vi t vong. Chuyn bun di y
c ghi nhn vo nm 1931 bi Alfred S. Reinhart, mt sinh vin y khoa Harvard b h van ng
mch ch sau thp tim thu nh. Mt m n, Reinhart pht hin nhng m xut huyt trn tay
tri v ngay lp tc t chn on mnh b vim ni tm mc nhim khun.
Ngay khi va ci b tay o tri ca chic o khoc, ti thy mt trong c tay mnh du hiu m
n tn khi la i ti cng khng th no qun. Trong tm mt ti l mi lm, hai chc m xut
huyt ti, ng knh 1mm, n knh khng mt, chng c tr l nh th dm thch thc
c nhng v thn trn nh Olympus Ti lic nhn m y mt ln na ri quay sang ch du
ng ng bn cnh, bnh tnh m rng: Em s cht trong vng su thng na.
CU HI:
1. Ba loi vi khun thng gp nht gy vim ni tm mc nhim khun l ,
, v khc.
2. Hai vi khun thng gp nht gy vim ni tm mc nhim khun trn bnh nhn thay
van nhn to l v .
179
3. Khng sinh c s dng trong iu tr vim ni tm mch nhim khun do lin cu
viridans gy ra vi dng khng trung bnh vi penicillin bao gm
hoc v phi hp vi .
4. Khng sinh c s dng trong iu tr vim ni tm mc do enterococci khng penicillin
l v .
5. Khng sinh c s dng trong iu tr vim ni tm mc nhim khun do Staphylococcus
epidermidis khng methicillin trn bnh nhn thay van nhn to l
thm , thm .
6. Khng sinh c s dng trong iu tr vim ni tm mc nhim khun do Staphylococcus
aureus nhy cm methicillin trn bnh nhn van tim t nhin l hoc
s dng hoc khng liu ngn ngy. .
7. Khng sinh c s dng trong iu tr vim ni tm mc nhim khun do Eikenella
corrodens l hoc hoc .
THAM KHO
Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial
therapy, and management of complications: a statement for healthcare professionals from the
Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular
Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular
Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society
of America. Circulation. 2005;111:e394e434.
Chopra T, Kaatz GW. Treatment strategies for infective endocarditis. Expert Opin Pharmacother.
2010;11:345360.
Horstkotte D, Follath F, Gutschik E, et al. Guidelines on prevention, diagnosis and treatment of
infective endocarditis executive summary; the Task Force on Infective Endocarditis of the
European Society of Cardiology. Eur Heart J. 2004;25:267276.
Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med. 2001;345:1318
1330.
Chng 23. Nhim khun lin quan n catheter trong lng mch
Th.S.DS. Lng Th Hi Vn-Khoa Dc - BV Nhn Dn Gia nh Tp H Ch Minh
Nu ln da ging nh bc tng thnh ca c th con ngi th cc catheter trong lng mch nh

nhng chic xe ph thnh lm ph v s bo v , cho php vi khun xm nhp vo dng mu
nm di d b tn thng. V cc catheter trong lng mch l thnh phn thit yu trong chm sc
bnh vin hin i nn cc nhim trng lin quan n catheter kh ph bin, xy ra vi t l
200.000 ca/nm ti Hoa K. R rng l vic nhn bit v iu tr ph hp nhng nhim khun ny
rt quan trng.
Vic chn on cc nhim trng lin quan n catheter trong lng mch cn nhiu kh khn do
vic xc nhn thng i hi vic rt hoc cy catheter. Tuy nhin, nhng nhim khun ny nn
c nghi ng bt k ai c catheter trong lng mch v st khng r nguyn nhn. S vim
nhim hoc tnh trng c m ch li ra ca catherter l c trng nhng khng chnh xc vi cc
nhim trng catheter. S tng trng ca vi khun t nui cy mu lm gia tng s nghi ng vi
cc nhim trng ny,
Hu ht cc nhim trng lin quan n catheter trong lng mch c gy ra bi h vi khun trn
da nhim vo catheter trong qu trnh t hoc di chuyn sau khi t. V th, khng c g l khi
coagulase-negative staphylococci (nht l Staphylococcus epidermidis) v Staphylococcus aureus
l cc tc nhn gy bnh thng lin quan n cc nhim trng catheter (Bng 23-1). nhng
bnh nhn suy gim min dch hoc bnh nng, trc khun gram m hiu kh cng gy ra nhng
nhim trng ny mt t l ng k.
Bng 23-1: Vi khun gy vim phi mc phi cng ng

Vi khun T l mc
Coagulase-negative staphylococci 32-41%
Staphylococcus aureus 5-14%
Trc khun gram m ng rut 5-11%
Pseudomonas aeruginosa 4-7%
181
Bng 23-2: Tr liu khng sinh theo kinh nghim trong nhim trng lin quan n
catheter trong lng mch
Khng methicillin khng ph bin
Penicillin khng t cu Nafcillin, oxacillin
Khng methicillin ph bin
Bnh nhn suy gim min dch hoc bnh nng
Thm cephalosporin Ceftazidime, cefepime
iu tr theo kinh nghim cc nhim trng lin quan n catheter trong lng mch tp trung vo t
cu. Vancomycin tr thnh tc nhn c la chn trong rt nhiu v tr (Bng 23-2 v Hnh
23-1). nhiu vng v bnh vin ni chng t cu khng methicillin him gp, oxacillin hoc
nafcillin c th c s dng. bnh nhn bnh nng hoc suy gim min dch, nhm
cephalosporin th h 3 hoc 4 (ceftazidime, cefepime) nn c thm vo bao ph trc khun
gram m ng rut v Pseudomonas aeruginosa. Mt khi vi khun gy bnh c nh danh t
cy mu hoc t chnh catheter, ch tr liu bng khng sinh nn tp trung vo vi khun c
nh danh. Tuy nhin, trong hu ht trng hp tr liu khng sinh n c l cha ; thng cn
phi loi b catheter.
Hnh 23-1: Tc ng ca cc tc nhn c dng trong iu tr cc nhim trng lin quan n

catheter trong lng mch
CU HI
1. ____________________________ Cc tc nhn vi khun in hnh gy ra cc nhim
trng lin quan n catheter trong lng mch l _____ , ___________________ v .
2. _____________ Trong trng hp ni m chng t cu khng methicillin khng ph bin,
______________v ____________l la chn khng sinh theo kinh nghim i vi
nhng nhim trng ny.
3. ______________________________________________________________ Tron
g trng hp ni m chng t cu khng methicillin ph bin, __________________ l
la chn khng sinh theo kinh nghim i vi nhng nhim trng ny.
4. ____________________ bnh nhn suy gim min dch hoc bnh nng, ___ hoc
______________________ nn c thm vo ch iu tr theo khng sinh i vi cc
nhim trng lin quan n catheter trong lng mch bao ph trc khun gram m ng
rut v Pseudomonas aeruginosa.
C THM
Ftkenheuer G, Cornely O, Seifert H. Clinical management of catheter-related infections. Clin
Microbiol Infect. 2002;8:545550.
Mermel LA, Farr BM, Sherertz RJ, et al. Guidelines for the management of intravascular
catheterrelated infections. Clin Infect Dis. 2001;32:12491272.
183
Chng 24: Nhim trng bng
Dch: DS. Dng Th Thanh, BV HNK Ngh An
Hiu nh: DS. V Th H
Nhim trng bng bao gm vim phc mc, nhim trng ng mt, p xe lch, vim rut tha,
vim ti tha v nhim trng sau khi mt tnh ton vn rut do chn thng hoc phu thut. Hu
ht cc hi chng thng thng l nhim trng ti v tr v trng ca bng do h vi khun ti
ng rut. V vy, chng thng l vi khun hn hp trong t nhin gy ra bi vi khun hiu kh,
trc khun ty kh gram m, trc khun k kh, cu khun hiu kh gram dng (Bng 24.1).
Nhng nhim khun ny c th kh nghim trng, thng xuyn gy nhim khun huyt v t
vong bnh nhn.
Bng 24.1 Cc vi khun gy nhim trng bng phc tp
Vi khun % bnh nhn
Escherichia coli 71
Klebsiella spp. 14
Pseudomonas aeruginosa 14
Proteus mirabilis 5
Enterobacter spp. 5
Vi khun k kh
Bacteroides fragilis 35
Bacteroides spp khc 71
Clostridium spp. 29
Peptostreptococcus spp. 17
Eubacterium spp. 17
Prevotella spp. 12
Fusobacterium spp. 9
Cu khun hiu kh gram dng
Streptococcus spp. 38
Enterococcus faecalis 12
Enterococcus faecium 3
Enterococcus spp. khc 8
Staphylococcus aureus 4
Triu chng ca nhim trng bng rt a dng ty thuc vo v tr v loi nhim trng bng.
Thng thng cc triu chng bao gm au bng, st, n lnh, bun nn v nn. Xt ngim cn
lm sng cho thy bch cu ngoi vi tng. Siu m bng cho thy bng chng ca tc rut, tc
nghn, p xe bng hoc c dch trong bng.
Nh cp, cc vi khun thng gy nhim khun bng l h vi khun ng rut. H vi

khun ny a dng ty thuc vo dch t bnh tt cng ng v cc chm sc y t lin quan. i
vi nhim trng bng mc phi ti cng ng, tc nhn gy bnh ch yu l trc khun rut
gram m hiu kh/ty kh, cu khun gram dng, trc khun k kh. La chn khng sinh iu tr
ty thuc vo mc nghim trng ca nhim khun. Khng sinh c th s dng n c hoc
c phi hp (Hnh 24.1 v Bng 24.2). Cc khng sinh c la chn bao gm nhm
carbapenem (ertapenem, imipenem, meropenem, doripenem), lactam/cht c ch lactamase
(ticarcillin/clavulanate, piperacillin/tazobactam), nhm cephalosporins (cefazolin, cefoxitin,
cefuroxime, ceftriaxone, cefotaxime, ceftazidime, cefepime), nhm quinolone (ciprofloxacin,
levofl oxacin, moxifloxacin), tigecycline, v metronidazole.
i vi nhim khun bng mc phi ti cc c s y t, nguyn nhn do vi khun khng thuc rt

ph bin, bao gm Pseudomonas aeruginosa, cu khun rut khng penicillin hoc khng
vancomycin, Staphylococcus aureus khng methicillin. Cc la chn khng sinh iu tr bao gm:
piperacillin/tazobactam mt mnh, mt loi carbapenem (imipenem, meropenem, doripenem),
hoc mt cephalosporin (ceftazidim, cefepime) phi hp vi metronidazole (Bng 24-2). Khi
nghi ng c t cu vng khng methicillin, phi hp thm vancomycin. Nhm aminoglycoside
(gentamicin, tobramycin, amikacin) nn c phi hp nu nghi ng c trc khun gram m
hiu kh/ty kh khng thuc.
Bng 24.2 Khng sinh kinh nghim iu tr nhim khun bng

Mc phi ti cng ng
i vi nhim khun nh v trung bnh
Cefoxitin, ertapenem, moxifl oxacin, tigecycline, ticarcillin/clavulanate hoc
(cefazolin, cefuroxime, ceftriaxone, cefotaxime, ciprofl oxacin, or levofloxacin) + metronidazole
i vi nhim khun nng
Imipenem, meropenem, doripenem, piperacillin/tazobactam hoc
(cefepime, ceftazidime, ciprofl oxacin, or levofloxacin) + metronidazole
Nhim khun do mc phi ti bnh vin
Lactam/-lactamase inhibitor combination Piperacillin/tazobactam
Hoc
Hoc
185
Cephalosporin th h 3 hoc 4 + Metronidazol Ceftazidime, cefepime
Cu hi:
1. Nhim trng bng do vi khun hn hp v ch yu gy ra bi 3 nhm vi khun c tm thy
ng rut bao gm: , . v..
2. Trc khun ty kh gram m thng gp trong nhim trng bng bao gm:..
3. Nhm khng sinh c s dng n c iu tr nhim trng bng nghim trng bi v
chng c ph tc dng trn 3 nhm vi khun khc nhau gy ra nhim trng bng l: . v
4. Nhim trng bng do mc phi ti bnh vin c th iu tr bng ceftazidim hoc cefepim,
nhng do cc khng sinh ny khng tc ng ln vi khun k kh, v vy khuyn co nn phi hp
cc khng sinh ny vi .
TI LIU C THM
Blot S, De Waele JJ. Critical issues in the clinical management of complicated intra-abdominal
infections. Drugs. 2005;65:16111620.
Montravers P, Gauzit R, Muller C, et al. Emergence of antibiotic-resistant bacteria in cases of
peritonitis after intraabdominal surgery affects the effi cacy of empirical antimicrobial therapy.
Clin Infect Dis. 1996;23:486494.
Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated
intraabdominal infection in adults and children: guidelines by the Surgical Infection Society and
the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:133164.
PHN V. CA LM SNG
Dch: BS. L Th Lin
DS. Nguyn Quang Vit, Cu sinh vin dc H Dc HN
Hiu nh: DS. V Th H
t c bt k k nng no cng i hi phi thc hnh v khng ngoi tr vic k n khng

sinh hp l. Trong phn ny, trnh by mt lot cc ca lm sng gip bn tip thu cc thng tin
t cc phn trc. Tr li cho cc cu hi v ca lm sng xem cui ca phn ny.
Ca lm sng 1
Mt ngi n ng 62 tui b st, n lnh, mt mi v ho ra m c m. ng y cng ni rng ng
y au ngc phi khi ho hoc ht th su. Mc d b bnh, kh nng hp thu thuc theo ng
ung ca ng y gn nh bnh thng. im ng ch trong bnh s v phu thut ca ng y l
cao huyt p v phu thut ni soi khp u gi tri 10 nm trc. ng y khng nhp vin ln
no khc k t khi phu thut u gi tri. Thuc duy nht ng y s dng l lisinopril. ng y
khng s dng bt k loi khng sinh no trong vng 3 thng qua. ng y l mt k ton, c s
dng bia/ru v khng ht thuc. ng y cng khng i du lch hoc tip xc vi cc loi chim
hoc ng vt khc ngoi ch ch cnh ca mnh.
Bnh nhn ny l mt ngi n ng hi bo ph vi thn nhit 38,5 C, huyt p 152/84, mch

74, nhp th 16, v bo ha oxy 98% iu kin phng. im ng ch khc sau khi thm
khm l ting c khi g thnh ngc, m th ph qun, khuynh hng bt ng ngc phi. D
dng c ng c v khng c ting thi ca tim. Xt nghim cho thy im ng ch l s lng
bch cu mu ngoi vi l 16.600 t bo/mm3 vi 75% bch cu trung tnh v 10% dng khc. Cht
in gii nm trong gii hn bnh thng v Glucose 155 mg/dL. X-quang lng ngc cho thy
vim phi thy v nghi vn trn dch phi phi.
Cu hi:
a. Chn on ca bn l g?
b. Nhng loi vi khun no thng gy nn triu chng ny?
c. Khng sinh no nn c s dng iu tr cho bnh nhn ny?
d. Loi khng sinh no bn s la chn iu tr cho bnh nhn ny nu ng y gim oxy
khng kh th vo v yu cu phi c nhp vin?
e. Loi khng sinh no bn s la chn iu tr cho bnh nhn ny nu ng y h huyt p,
cn h tr vn mch v c chuyn vo n v chm sc tch cc?
f. Loi khng sinh no bn s la chn iu tr cho bnh nhn ny nu sau mu mu c
s xut hin ca Streptococcus pneumoniae?
g. Loi khng sinh no bn s la chn iu tr cho bnh nhn ny nu kt qu xt nghim
mu nc tiu dng tnh vi Legionella pneumophila?
Ca lm sng 1
a. Bnh nhn ny b vim phi, bng chng l mi khi pht st, n lnh, ho c m, s
lng bch cu mu ngoi vi tng cao v thm nhim trn X-quang lng ngc. Vim phi
187
c phn loi l vim phi mc phi ti cng ng do bnh nhn gn y khng nhp
vin hoc tip xc vi mi trng chm sc sc khe hay khng s dng khng sinh.
b. Vi khun ph bin nht gy nn vim phi mc phi ti cng ng ngi ln l
Streptococcus pneumoniae, Haemophilus in uenzae, Legionella spp., Mycoplasma
pneumoniae, vi khun Gram m hiu kh khc, Chlamydophila pneumoniae, v
Staphylococcus aureus. Tui ca bnh nhn, ho c m v vim phi thy l mt trng
hp in hnh, tri ngc vi trng hp khng in hnh. Tuy nhin, nhng khc bit
lm sng c chng minh l khng ng tin cy v s la chn iu tr khng nn da
vo chng.
c. Vim phi bnh nhn ny nh v c th c iu tr ngoi tr. ng y khng c nguy
c nhim S. pneumoniae khng penicillin. La chn khng sinh thch hp l mt macrolid
ng ung (azithromycin, clarithromycin, erythromycin) hoc doxycycline.
d. Nu vim phi bnh nhn ny l nghim trng phi nhp vin iu tr, bnh nhn
nn c tim truyn tnh mch bao gm c mt khng sinh nhm macrolide
(azithromycin, clarithromycin, erythromycin) v mt khng sinh nhm -lactam
(cefotaxime, ceftriaxone, ampicillin liu cao). Mt quinolone tim truyn tnh mch vi
hot tnh khng lin cu (moxifloxacin, levofloxacin) cng s l mt la chn thch hp.
e. Nu bnh ca bnh nhn l nghim trng v yu cu iu tr mt n v chm sc tch
cc, bnh nhn s c tim truyn tnh mch -lactam (cefotaxime, ceftriaxone, liu cao
ampicillin/sulbactam) kt hp vi mt nhm macrolide (azithromycin) hoc quinolone vi
hot tnh khng lin cu (moxifloxacin, levofloxacin). Lu rng bnh nhn ny khng c
yu t nguy c b Pseudomonas aeruginosa hoc nhim trng MRSA, do khng sinh
khng MRSA v khng trc khun m xanh khng c ch nh.
f. S xut hin ca S.pneumoniae trong mu ca bnh nhn cho thy vim phi ca bnh
nhn ny l do vi khun ny. Trong trng hp ny, phc iu tr c th c thu hp
v tp trung vo tc nhn gy bnh ny. iu tr khng sinh thch hp s l liu cao
penicilin G. Cephalosporin th h 2 hoc th h 3 cng s thch hp. Lu rng mt vi
bo co cho thy rng nhng bnh nhn b vim phi do ph cu trong mu c kt qu tt
hn vi phc phi hp mt -lactam vi mt khng sinh nhm macrolide
(azithromycin) so vi ch s dng -lactam, v vy iu tr kt hp c th c xem xt.
g. Nu xt nghim chn on cho thy vim phi ca bnh nhn ny l do Legionella spp.,
iu tr s nhm mc tiu chng li vi khun ny. Khng sinh thch hp s l azithromycin
hoc quinolone (levofloxacin hoc moxifloxacin).
Ca lm sng 2
Mt ph n 68 tui c nhp vin lm phu thut ct b rut kt sau khi c chn on ung
th i trng khng di cn. Cuc phu thut c thc hin vo ngy hm sau. Sau phu thut tnh
trng sc khe ca c y tr nn phc tp v chc nng h hp km do bnh phi tc nghn mn
tnh. Kt qu l c y vn phi th my. Vo ngy hu phu th 6, c y st, m v dch tit ng
h hp tng ng k. Kim tra ng h hp ng ch l c ran ngy 2 bn. S lng bch cu
ngoi vi tng ln n 18.200 t bo/mm3 vi 81% bch cu trung tnh. X quang lng ngc cho thy
s pht trin ca cc vt thm nhim loang l 2 bn. Kim tra s b mu dch kh qun cho thy
nhiu bch cu trung tnh v trc khun Gram m.
Cu hi:
b. Nhng loi vi khun no thng gy nn triu chng ny?
c. Loi khng sinh no nn c s dng iu tr cho bnh nhn ny?
d. Loi khng sinh no nn c s dng iu tr cho bnh nhn ny nu dch kh qun c
c trc khun Gram m v cu khun Gram dng?
e. Loi khng sinh no nn c s dng iu tr cho bnh nhn ny nu sau khi nui cy
thy s xut hin ca Pseudomonas aeruginosa?
f. Loi khng sinh no nn c s dng iu tr cho bnh nhn ny nu sau khi nui cy
thy s xut hin ca Staphylococcus aureus?
Tr li
a. Bnh nhn ny mc vim phi, bng chng l s khi u st, tng sn xut dch tit m
ng h hp, s lng bch cu mu ngoi vi cao v vt thm nhim trn X quang lng
ngc. Bnh vim phi phn loi l vim phi mc phi ti bnh vin v triu chng xut
hin sau khi bnh nhn bnh vin.
b. Vim phi ca bnh nhn ny xut hin sau khi c iu tr ti bnh vin trong 8 ngy.
Do y l bnh vim phi mc phi ti bnh vin khi pht mun. Vi mt bnh nhn
nh vy, ngi ta phi c bit quan tm n Pseudomonas aeruginosa, Acinetobacter
spp., trc khun gram m ng rut khng khng sinh v MRSA. S xut hin ca nhiu
trc khun gram m trong dch kh qun cho thy c P. aeruginosa hoc trc khun gram
m ng rut khng khng sinh.
c. Phc iu tr thch hp s bao gm mt i din t mt trong hai nhm thuc khng
sinh. Nhm 1 gm cc cephalosporin khng trc khun m xanh (ceftazidime, cefepime),
cc carbapenem (imipenem, meropenem) v penicillin ph rng/kt hp thuc c ch -
lactamase (piperacillin/tazobactam). Nhm 2 gm cc quinolone (ciprofloxacin,
levofloxacin) v cc aminoglycoside (gentamycin, tobramycin, amikacin).
d. S xut hin ca cu khun gram dng trong dch kh qun cho thy c Staphylococcus
aureus. Bi v t l MRSA cao mt n v chm sc tch cc, thuc khng sinh c hiu
qu chng li cc sinh vt ny nn c la chn. V vy, mt phc thch hp s l s
kt hp ca cc loi thuc khng sinh c m t trong cu "c" vi s b sung ca
linezolid hoc vancomycin.
e. S pht trin ca P.aeruginosa t dch kh qun cho thy vi khun ny l nguyn nhn ca
bnh vim phi. Phc iu tr thch hp s bao gm hai i din vi hot tnh khng trc
189
khun m xanh, chng hn nh mt cephalosporin khng TKMX (ceftazidime, cefepime)
hoc piperacillin phi hp vi ciprofloxacin hoc aminoglycoside (gentamycin,
tobramycin, amikacin). La chn thc t nn da vo thng tin khng thuc ti a phng
v s phi nhim vi khng sinh trc ca bnh nhn ny. Lu piperacillin s c s
dng thay cho phi hp piperacillin/tazobactam v tazobactam khng c hot tnh chng li
cc -lactamase ca P. aeruginosa. Ngoi ra, cn nh l ciprofloxacin c hot tnh khng
TKMX tt nht ca cc quinolone.
f. S pht trin ca S. aureus t dch kh qun cho thy rng vi khun ny l nguyn nhn ca
bnh vim phi. Phc iu tr thch hp s l linezolid hoc vancomycin.
Ca lm sng 3
Mt ngi ph n 23 tui c i sng quan h tnh dc tch cc ni rng hin c y b kh tiu,
thng xuyn v tiu mu c 3 ngy. Khng c du hiu ca st, n lnh, bun nn, nn
ma hoc au mn sn v c y chc chn rng c y khng mang thai. im ng ch trong
bnh s ca c y l vim bng quang 1 nm trc. Thm khm cho thy khng st hoc au
nhc ni gc sn v ct sng. Que th nc tiu dng tnh vi leukocyte esterase.
Cu hi:
b. y l nhim trng phc tp hay khng c bin chng?
c. Bn s s dng khng sinh no iu tr cho bnh nhn ny?
d. Loi khng sinh no nn c s dng iu tr cho bnh nhn ny nu c y sng ti 1
khu vc m 40% cng ng mc Escherichia coli khng vi trimethoprim-
sulfamethoxazole?
e. Loi khng sinh no nn c s dng iu tr cho bnh nhn ny nu c y b tiu
ng v nhum Gram nc tiu cho thy nhiu trc khun Gram m?
Ca lm sng 3
a. Bnh nhn ny b vim bng quang cp tnh, bng chng l cc triu chng ca tiu kh,
thng xuyn v que th nc tiu dng tnh. S vng mt ca st, n lnh, bun nn,
nn, au mn sn cho thy c y khng c du hiu ca vim b thn.
b. Nhim trng ng tit niu ny s c phn loi l vim bng quang cp tnh "khng c
bin chng" v bnh nhn tr, khe mnh, khng mang thai, khng phi nhp vin v
khng c bng chng v cu trc bt thng ca ng tit niu.
c. Phc iu tr thch hp cho bnh nhn ny l mt liu trnh 5 ngy ca nitrofurantoin
hoc c th l mt t 3 ngy ca trimethoprim-sulfamethoxazole ng ung nu c sng
trong mt khu vc, trong t l khng ca cc tc nhn trong nc tiu vi thuc ny
thp hn 20%.
d. Nu bnh nhn ny sng ti mt khu vc m t l khng trimethoprim- sulfamethoxazole
l ph bin, nitrofurantoin s l la chn iu tr thch hp.
e. Nu bnh nhn c chn on trc mc bnh tiu ng, bnh nhn c xu hng b
nhim trng bi nhiu loi vi khun v c th gy ra nhim trng ng tit niu, do
bnh nhn s b phn loi l mt vim bng quang cp tnh "phc tp". Bi v nhim trng
nh, c c th c iu tr bng khng sinh ung. Ciprofloxacin s l mt la chn tt v
n c hiu qu chng li nhiu loi trc khun gram m c th gy nhim trng ny, k c
Pseudomonas aeruginosa v nhiu loi Enterobacteriaceae.
191
Ca lm sng 4
Mt ngi ph n 26 tui c i sng quan h tnh dc tch cc ni rng hin c y b st, n lnh,
kh tiu, thng xuyn v au mn sn t 6 ngy nay. C y cng bo rng bun nn v nn
nhiu ln v khng th duy tr ung thuc c. im ng ch trong bnh s ca c y l c y
thng (khng m) con gi hin 3 tui. C y ni rng hin c y hin khng mang thai.
Cc ch s cn quan tm nh sau: thn nhit 38,7C, huyt p t th nm 98/66 v mch 88, huyt
p t th ng 88/55 v mch 101, nhp th 13. im ng ch ca khm lm sng l au nhc
ni gc sn v ct sng khi thm khm pha bn tri. Phn tch phng th nghim cho thy s
lng bch cu trong mu ngoi vi 26.200 t bo/mm3 vi 82% bch cu trung tnh v 15% dng
khc. Cht in gii trong gii hn bnh thng v Glucose 93 mg/dL. Mu nc tiu ch ra rng
i m v >100.000 vi khun.
Cu hi:
b. y l nhim trng phc tp hay khng c bin chng?
c. Loi khng sinh m bn la chn iu tr cho bnh nhn ny?
Ca lm sng 4
a. Bnh nhn ny b vim b thn cp tnh, bng chng l cc triu chng st, n lnh,
kh tiu, thng xuyn v au mn sn.
b. Trng hp ny, vim b thn cp tnh s c phn loi l khng c bin chng v
bnh nhn l tr, khe mnh, khng mang thai, khng phi nhp vin v khng c bng
chng v cu trc bt thng ca ng tit niu.
c. Bi v bnh nhn ny mt nc v khng th s dng thuc ng ung, c y cn
c nhp vin v tim truyn tnh mch khng sinh cng nh b nc. Da trn kinh
nghim, phc iu tr khng sinh thch hp l mt quinolone (ciprofloxacin,
levofloxacin); aminoglycoside (gentamycin, tobramycin, amikacin) c hoc khng c
ampicillin; mt penicilin ph rng (piperacillin) c hoc khng c mt aminoglycoside;
cephalosporin th h 3 (ceftriaxone, cefotaxime) c hoc khng c mt
aminoglycoside; hoc mt carbapenem (imipenem, meropenem, doripenem, ertapenem
Ca lm sng 5
Mt ph n 17 tui c i sng quan h tnh dc tch cc ni rng hin c y b st, n lnh, au
bng di v c dch tit m o sut 1 tun nay. Khng c du hiu bun nn, nn ma v tiu
chy. iu ng ch trong bnh s ca c y l 2 ln nhim Chlamydia trong vng 2 nm qua.
Cc ch s cn quan tm nh sau: thn nhit 37,4C, huyt p 126/78, mch 72 v nhp th l 11.
im ng ch ca khm lm sng l au bng di 2 bn m khng au ton b. Thm khm
ph khoa, au lc lay ng c t cung, au phn ph 2 bn, tit dch do vim c t cung nhy m
c ghi nhn. Xt nghim cho thy mt lng ln bch cu mu ngoi vi 8.300 t bo/mm 3 vi
60% bch cu trung tnh v khng xut hin dng khc. Glucose v cc cht in gii nm trong
gii hn bnh thng.
Cu hi:
b. Nhng nguyn nhn c th gy nn nhim trng bnh nhn ny?
c. Bn s s dng khng sinh no iu tr cho bnh nhn ny?
d. Nu bn tnh ca c y sau c pht hin nhim Chlamydia trachomatis, loi khng
sinh no nn c s dng iu tr cho anh ta?
e. Nu bn tnh ca c y sau c pht hin nhim Neisseria gonorrhoeae, loi khng
sinh no nn c s dng iu tr cho anh ta?
193
Tr li Ca lm sng 5
a. Bnh nhn ny b vim vng chu (VVC), bng chng l cc triu chng st, n lnh, au
bng di v au lc lay ng c t cung, au phn ph 2 bn, tit dch do vim c t cung
nhy m.
b. Cc vi khun thng ly truyn qua ng tnh dc nht l Neisseria gonorrhoeae v
Chlamydia trachomatis. Nhiu vi khun khc thng xuyn c phn lp t cc tn
thng VVC, k c Bacteroides v Peptostreptococcus spp. nh Escherichia coli,
Gardnerella vaginalis, Haemophilus influenzae v nhm lin cu nhm B. Trong s ny, vi
khun k kh c nhiu kh nng ng mt vai tr trng yu trong sinh bnh hc ca VVC,
v nhiu chuyn gia ngh rng khng sinh c hiu qu chng li cc vi khun k kh nn
c dng trong cc phc iu tr VVC.
c. Bi v bnh ca bnh nhn ny tng i nh, c c th iu tr ngoi tr. Mt phc
khng sinh thch hp s l mt liu tim bp duy nht ca mt cephalosporin (ceftriaxone,
cefotaxime, cefoxitin + probenecid) cng vi doxycycline ng ung. Vic b sung
metronidazole ng ung cng l la chn hp l.
d. Vim niu o do C. trachomatis khng bin chng c iu tr bng doxycyclin,
azithromycin, ofloxacin hoc levofloxacin.
e. Bnh lu c iu tr bng ceftriaxone hoc cefixime. Tt c cc bnh nhn b bnh lu
cng nn c iu tr Chlamydia.
Ca lm sng 6
Mt ngi n ng than phin v cc triu chng st, n lnh, bun nn, nn ma, bn chn v
cng c trong 24 gi qua. ng y ni rng ng y b nght mi v ho trong 1 tun trc v
khi. iu ng ch trong bnh s ca ng y l cao huyt p v nghin ru. Qua thm
khm thy thn nhit 38,7C, au np gp ca c, nghi vn ph gai th, v c th nh hng bn
thn v v tr nhng khng nhn bit thi gian trong nm. Do lo ngi v cc vn h thn kinh
trung ng, quyt nh chp ct lp u (chp CT) s c thc hin trc khi chc d ty sng.
Cu hi:
a. Bn nn quan tm n loi nhim trng no?
b. Loi vi khun no thng gy nn nhim trng ny?
c. C nn cho bnh nhn ung khng sinh trc khi thc hin chp CT u?
d. Nu quyt nh dng khng sinh l ph hp, loi khng sinh no nn c s dng?
Chp CT u c thc hin v cho thy khng c bng chng ca tn thng h thn kinh trung
ng. Chc d ty sng cng c thc hin, trong dch no ty vi cc thng s sau: bch
cu 412 t bo/mm3 (96% bch cu trung tnh); protein 110 mg/dL; glucose 23 mg/dL (ng thi
glucose huyt thanh l 98 mg/dL). Nhum Gram kim tra thy xut hin cu khun Gram dng.
e. Nhng vi khun no c th gy nn triu chng ca bnh nhn ny?
f. Nhng thay i no bn s thc hin trong phc iu tr ca bnh nhn ny?
Vi ngy sau , phng kim nghim vi sinh bo co rng S. pneumoniae nhy cm vi penicillin
c pht trin t dch no ty.
g. Nhng thay i no bn s thc hin trong phc iu tr ca bnh nhn ny?
h. Nhng loi khng sinh no bn s chn cho bnh nhn ny nu kt qu nhum Gram xut
hin nhng cp cu khun Gram m.
i. Nhng loi khng sinh no bn s chn cho bnh nhn ny nu kt qu nhum Gram xut
hin trc khun Gram dng.
Tr li Ca lm sng 6
a. Bnh nhn ny c th c vim mng no cp do vi khun, bng chng l s khi pht cp
tnh ca st, n lnh, bun nn, nn ma, nhc u, bn chn, cng c. Kim tra dch no
ty l cn thit chc chn vic chn on.
b. i vi bnh nhn trng thnh, bnh vim mng no cp tnh thng c gy ra bi
Streptococcus pneumoniae hoc Neisseria meningitidis. i vi bnh nhn cao tui nh
bnh nhn ny, Listeria monocytogenes v trc khun gram m hiu kh cng l mt mi
quan tm.
c. Ngay c s chm tr vi gi iu tr c th c mt tc ng bt li n kt qu iu tr ca
cc bnh nhn b vim mng no cp do vi khun. V l do ny, iu tr khng sinh khng
nn ch i cc kt qu ca hnh nh thn kinh m nn bt u sm. Lu rng hu ht
cc chuyn gia cng s bt u iu tr steroid trc hoc cng lc bt u dng khng
sinh.
d. Da trn kinh nghim, iu tr bnh nhn ny s bao gm mt cephalosporin th h ba
(ceftriaxone hoc cefotaxime) iu tr N. meningitidis v hu ht cc chng S.
pneumoniae, cng nh trc khun gram m hiu kh. Vancomycin nn c thm vo
iu tr cc chng S. Pneumoniae khng penicillin mnh. Bi v bnh nhn ny trn 50
tui, ampicillin cng nn c ch nh iu tr L. monocytogenes.
e. Kt qu chc d ty sng chn on vim mng no cp do vi khun. Cc cp cu khun
Gram dng xut hin khi nhum dch no ty cho thy nguyn nhn c kh nng l S.
pneumoniae. Nu bnh nhn l tr s sinh, phi cn quan tm n Streptococcus
agalactiae, nhng vim mng no m gy nn bi vi khun ny him gp ngi ln.
f. Vim mng no do S. pneumoniae c iu tr bng cephalosporin th h ba v
vancomycin, do ampicillin nn ngng s dng.
g. Vim mng no gy ra bi S.pneumoniae nhy cm penicillin c th c iu tr bng
penicillin hoc cephalosporin th h ba.
h. Dch no ty cha cp cu khun Gram m ch ra rng N. meningitidis l nguyn nhn gy
bnh vim mng no. Bnh nhn nn c iu tr bng penicillin G hoc cephalosporin
th h ba (ceftriaxone, cefotaxime).
i. Dch no ty c trc khun Gram dng cho thy L. monocytogenes l nguyn nhn gy
nn bnh vim mng no. Bnh nhn nn c iu tr bng ampicillin kt hp vi
gentamicin.
Ca lm sng 7
Ngi bnh n 56 tui than phin nhng m mn nh gy au trn chn phi. Nm ngy trc,
mt vt gip da xut hin trn bn chn ngi bnh sau khi i i giy mi. Ba hm trc, vng
da quanh ch gip b nh. Nhng ngy sau, vng mn lan rng, lan n hu ht bn chn v
mt c chn ngi bnh, n bnh nhn kh khn ng trn i chn v au. Ngi bnh cng
ghi nhn b st, n lnh v rt run trong 24 gi qua. Ngi bnh c tin s bnh tng huyt p
195
ng k, lipid mu cao v suy tuyn gip. Ngi bnh c k cc thuc hydrochloro-thiazide,
lovastatin v levothyroxine. Thnh ph ngi bnh sng c mt t l cao nhim khun mc phi
trong cng ng i vi Staphylococcus aureus (MRSA) khng methicillin. Du hiu sinh tn (cc
ch s sinh l chnh ca ngi bnh): nhit , 39,1 C; mch 96 nhp mi pht; nhp th 16
nhp mi pht; huyt p, 123/74 mm Hg. Khm thc th thy ban , nng, hi mm, chn phi
ngi bnh b sng v lan rng ln lng chng bp chn. Khng c bng nc. ng mach mu
bn chn nguyn vn, dng nh c cm gic trn vng pht ban. Ngi bnh th i li khng kh
khn.
CU HI
b. Nhng vi khun no thng gy nhim khun ny?
c. Nhng khng sinh no, theo kinh nghim bn s s dng iu tr bnh ny?
d. Nu nui cy mu sau mc vi khun Streptococcus pyogenes, bn s s dng khng sinh no
iu tr cho ngi bnh ny?
e. Nu nui cy mu sau mc vi khun S. aureus nhy cm vi methicillin, bn s s dng
khng sinh no iu tr cho ngi bnh ny?
Ca lm sng 8
Mt ngi m a con gi 5 tui i khm tai phi b au qua 72 gi. Mt ng nghip ca bn
khm cho bnh nhi 2 ngy trc v chn on chu b b vim tai gia cp tnh ti thi im
. ng ni vi m c b cn thn theo di v khm li nu triu chng khng sau 2 ngy
ti. T , bnh nhi au tai ko di hin ti b st. Bnh s 24 thng trc bnh nhi b nhim
khun tai trc r rt. Khm bnh thy nhit chu b 38,8 C; Du hiu sinh tn (cc ch s
sinh l chnh ca ngi bnh) trong gii hn bnh thng. Mng nh phi xng v vim. Khng c
bng chng vim kt mc.
CU HI
b. Nhng vi khun no thng gy nhim khun ny?
c. Nhng khng sinh no, theo kinh nghim bn s s dng iu tr bnh ny?
Khi hi thm, ngi m cho bit ngi bnh gy y c dng amoxicillin iu tr nhim
khun tai, nhng b ni pht ban ngay sau dng thuc. Ngi m ni vi bc s pht ban khng
nga, bc s khm v kt lun khng phi l pht ban.
CU HI
d. Khng sinh no bn s s dng iu tr cho bnh nhi ny?
e. Khng sinh no bn s s dng nu bnh nhi c tin s pht ban (m ay) lin qua ti vi
amoxicillin?
Ca lm sng 9
Ngi bnh n 38 tui biu hin bnh s st 2 tun, n lnh v mt mi. Tin s bnh qu kh
rng mc khng u, nn phi nh mt s rng 6 tun trc khi nhp vin v st do vim khp tr
em, mc d ngi bnh khng tun th iu tr khng sinh d phng trc khi lm cc th tc.
Ngi bnh lm k ton v i khi ung ru ngoi qun, khng ht thuc hoc dng cc thuc
gy nghin hoc ph thuc.
Ngi bnh gy, thn nhit 38,2 C, huyt p 122/54, mch 83 v mnh v nhp th 12
ln/pht. Khm thy khng r ting thi tm trng rt sm pha trn ra xng c III/VI khng
xut hin trong ln khm trc. Ghi nhn xut huyt kt mc. nh gi xt nghim c bch cu
mu ngoi vi 10.600 t bo/mm t l 65% bch cu trung tnh v c hemoglobin 12 g/dL. Cht
in gii trong gii hn bnh thng v glucose 95 mg/dL. Phn tch nc c huyt niu. Siu m
tim thy tro ngc ng mch ch c si mt l van ng mch ch.
CU HI
b. Nhng vi khun no ph bin nht gy ra hi chng ny l g?
c. Nui cy mu v quyt nh iu tr theo kinh nghim cho ngi bnh trong khi ch i kt qu
nui cy. Nhng khng sinh no theo kinh nghim bn s s dng iu tr cho ngi bnh ny?
d. Nu cy mu sau pht hin nhm viridans streptococci nhy cm hon ton vi penicillin
(nng c ch ti thiu 0,12 g/mL), nhng khng sinh no bn s s dng iu tr cho ngi
bnh ny?
e. Nu cy mu sau pht hin S. aureus khng methicillin, nhng khng sinh no bn s s
dng iu tr cho ngi bnh ny?
f. Nu cy mu sau pht hin vi khun nhy cm vi penicillin v aminoglycosid, nhng khng
sinh no bn s s dng iu tr cho ngi bnh ny?
Ca lm sng 10
Ngi bnh nam 74 tui biu hin bnh s st 1 tun, n lnh v ang gia tng kh th. Tin s
bnh qu kh thy r thay van hai l nhn to 5 thng trc khi nhp vin. ng l nhn vin qun
l ngn hng v hu. ng tha nhn ung ru va phi v ht mt gi thuc l mi ngy. Du
hiu sinh tn (cc ch s sinh l chnh ca ngi bnh): thn nhit 38,4 C, huyt p 122/75,
mch 92 v nhp th 19 ln/pht. Khm thy phng tnh mch mch cnh khng r rng, ting ran
khng lin tc hai y phi v ting thi tm trng c mun.
nh gi xt nghim c bch cu mu ngoi vi 12.400 t bo/mm t l 70% bch cu trung tnh
v c hemoglobin 13,2 g/dL. Cht in gii trong gii hn bnh thng v glucose 89 mg/dL. Siu
m tim thy thiu nng ng mch ch c cc ch si.
CU HI
c. Nui cy mu v quyt nh iu tr theo kinh nghim cho ngi bnh trong khi ch i kt qu
nui cy. Nhng khng sinh no theo kinh nghim bn s s dng iu tr cho ngi bnh ny?
d. Nu cy mu sau pht hin nhm Staphylococcus epidermidis khng vi methicillin, nhng
khng sinh no bn s s dng iu tr cho ngi bnh ny?
e. Nu cy mu sau pht hin S. aureus nhy cm vi methicillin, nhng khng sinh no bn s
s dng iu tr cho ngi bnh ny?
197
f. Nu cy mu sau pht hin Haemophilus aphrophilus, nhng khng sinh no bn s s dng
Ca lm sng 11
Ngi bnh n 85 tui trong phng hi sc cp cu sau phu thut ct i trng do ung th rut
kt. Sau phu thut 3 ngy bn c yu cu khm cho b v b st.
Ngi bnh c th my v dng thuc an thn. Thn nhit 38,6 C, huyt p 128/75 v mch
96. B ang nhn c h tr h hp ti thiu v iu dng bo co dch tit ng h hp phi
ht khng nhiu. Khm thy phi sch v bng ngi bnh mm. Cc vt thng phu thut ch
hng ti thiu m khng c m xng hoc chy dch v phn c trong ti hu mn nhn to.
ng thng Foley c t. Ngi bnh khng b sng, nhng c thot m t cc im xut pht
ng thng xng i triple-lumen. nh gi xt nghim c bch cu mu ngoi vi 12.400 t
bo/mm t l 70% bch cu trung tnh. Cht in gii, glucose, nc tiu trong gii hn bnh
thng. X quang ngc cho thy khng c bng chng v s thm nhim.
CU HI
c. Bn yu cu cy mu thu c t cc ng thng c g b v cc u ng thng c gi nui
cy. Trong khi ch i kt qu nui cy. Nhng khng sinh no theo kinh nghim bn s s dng
d. Sau khi xem xt thm cc biu ca ngi bnh, bn thy ngi bnh c tin s h thng
bnh lupus ban v iu tr liu cao corticoid mt thi gian. Nhng khng sinh no bn s s
dng iu tr theo kinh nghim cho ngi bnh ny?
e. Nu cy mu sau pht hin S. aureus nhy cm vi methicillin, nhng khng sinh no bn s
s dng iu tr cho ngi bnh ny?
f. Nu cy mu sau pht hin S. aureus nhy cm vi methicillin, nhng ngi bnh c tin s
phn ng phn v amoxicilin, nhng khng sinh no bn s s dng iu tr cho ngi bnh ny?
Ca lm sng 12
Ngi bnh nam 21 tui biu hin bnh s 4 ngy au bng d di m ban u tp trung gc
phn t pha di bn phi, nhng hin ti au lan ta hn. Anh cng ghi nhn c st, n lnh,
bun nn v nn. Tin s bnh qu kh ca mnh l khng r rng v anh khng c dng bt c
loi thuc no.
Thn nhit 38,5 C, huyt p 90/53 v mch 121. Khm thy thc th thy ngi bnh au bng
lan ta r rng vi bng gng cng. Khng nghe c nhu ng rut. nh gi xt nghim thy
c bch cu mu ngoi vi 23.100 t bo/mm vi 95% bch cu trung tnh. Cht in gii, glucose,
nc tiu trong gii hn bnh thng. X quang bng cho thy tc rut mc kh trong cht
lng, bng kh t do. Siu m kim tra ph hp vi vim rut tha b v. Ngi bnh c chun
b ngay cho phu thut.
CU HI
a. Ngi bnh hin b vim phc mc th pht v v rut tha. Cc vi khun ph bin nht gy ra
hi chng ny l g?
b. Nhng khng sinh no theo kinh nghim bn s s dng iu tr cho ngi bnh ny?
c. Nu ngi bnh ny b bnh x nang v gn y c nhp vin v trong qu kh iu tr
khng sinh nhim khun ng h hp nhiu t, nhng khng sinh no bn s s dng iu tr
cho ng?
199
PHN VI. HI V TR LI
SVD. Nguyn L Khuynh Trng H Y Dc Hu
Hiu nh: DS. V Th H
1. Khng sinh no sau y khng thuc nhm -lactam
a. Ampicillin
b. Meropenem
c. Ceftriaxone
d. Vancomycin
e. Aztreonam
2. Khng sinh no di y t tc ng ln vi khun k kh
a. Imipenem
b. Metronidazole
c. Ceftriaxone
d. Clindamycin
e. Amoxicillin/clavulanate
3. Khng sinh no sau y c th s dng ngi c tin s d ng penicilline
a. Aztreonam
b. Ertapenem
c. Cefazolin
d. Piperacillin/tazobactam
e. Cefotetan
4. Khng sinh no sau y khng hu dng iu tr nhim khun ng rut
a. Penicillin
b. Cefazolin
c. Ampicillin
d. Gentamicin
e. Vancomycin
5. Khng sinh quinolone no sau y hu dng nht khi chng li Pseudomonas aeruginosa?
a. Levofloxacin
b. Moxifloxacin
c. Gatifloxacin
d. Gemifloxacin
e. Ciprofloxacin
6. Rifapin hu dng trong d phng v iu tr cc loi vi khun sau ngoi tr
a. Staphylococcus aureus
b. Staphylococcus epidermidis
c. Bacteroides fragilis
d. Neisseria meningitidis
e. Mycobacterium tuberculosis
201
7. Nhim khun nghim trng c gy bi loi vi khun no sau y thng c iu tr bi mt
khng sinh duy nht
a. Treponema pallidum
b. Brucella melitensis
c. Pseudomonas aeruginosa
d. Mycobacterium tuberculosis
e. Helicobacter pylori
8. Khng sinh no sau y khng hu dng trong iu tr nhim khun do
Mycobacterium avium
a. Clarithromycin
b. Isoniazid
c. Ethambutol
d. Rifabutin
e. Ciprofloxacin
9. Khng sinh no sau u hu dng khi iu tr nhim khun bi Clostridium difficile?
a. Clindamycin
b. Imipenem
c. Penicillin
d. Metronidazole
e. Piperacillin/tazobactam
10. Khng sinh no sau y hu dng khi iu tr nhim khun do Escherichia coli
loi tit ra -lactam ph rng?
a. Ceftriaxone
b. Ceftazidime
c. Meropenem
d. Aztreonam
e. Piperacillin
11. Khng sinh no sau y khng ngn chn s hnh thnh mng t bo vi khun?
a. Gentamicin
b. Aztreonam
c. Imipenem
d. Vancomycin
e. Ampicillin
12. Penicillin vn thng c dng chng li nhng vi khun sau y NGOI TR
a. Treponema pallidum
b. Streptococcus pyogenes
c. Clostridium perfringens
d. Neisseria meningitidis
e. Staphylococcus aureus
13. Vi khun no sau y nhy cm vi vancomycin?
a. Bordetella pertussis
b. Clostridium difficile
c. Pseudomonas aeruginosa
d. Haemophilus influenzae
e. Enterobacter aerogenes
14. Tt c cc tc nhn di y iu u hu hiu chng li Haemophilus influenzae NGOI

TR:
a. amoxicillin/clavulanate
b. cefuroxime
c. ampicillin
d. doxycycline
e. cefotaxime
15. Khng sinh no sau y an ton cho tr em
a. ciprofloxacin
b. azithromycin
c. tetracycline
d. gemifloxacin
e. doxycycline
16. Tt c cc phn ng c hi sau y u lin quan n khng sinh nhm aminoglycoside ngoi
tr:
a. Suy gim thnh gic
b. Gy c cho cc tiu th thn (c cho thn)
c. c tnh ln tin nh
d. Tc mt
e. Suy gim chc nng thn
17. Pyrazinamide hu dng trong iu tr nhim khun?
a. Mycobacterium tuberculosis
b. Mycobacterium avium phc hp
c. Mycobacterium leprae
d. Rickettsia rickettsii
e. Legionella pneumophila
18. Cc bnh ly qua ng tnh dc bi chlamydia c th iu tr bi cc khng sinh sau NGOI
TR ?
a. Doxycycline
b. Azithromycin
c. Ofloxacin
d. Levofloxacin
e. Ceftriaxone
19. Cc ch nh theo kinh nghim (Empiric use) ca vancomycin cho bnh nhn vim ni tm mc
nhim khun s tht bi khi c s xut hin ca vi khun no sau y?
203
c. Lin cu khun nhm viridans
d. Vi khun ng rut (Enterococci)
e. Vi khun HACEK
20. Khng sinh no sau y tc ng ln ribosome ca vi khun?
a. isoniazid
b. vancomycin
c. tetracycline
d. levofloxacin
e. trimethoprim+sulfamethoxazole
21. Khng sinh no sau y khng c s dng trong iu tr nhim khun do Borrelia
burgdorferi?
a. doxycycline
b. clindamycin
c. amoxicillin
d. cefuroxime
e. ceftriaxone
22. Doxycycline hu dng khi iu tr nhim cc loi vi khun di y NGOI TR
a. Leptospira interrogans
b. Brucella abortus
c. Chlamydia trachomatis
d. Pseudomonas aeruginosa
e. Rickettsia rickettsii
23. Khng sinh no sau y tc ng ln RNA polymerase ca vi khun?
a. Cefotetan
b. Amikacin
c. Rifampin
d. Azithromycin
e. Daptomycin
24. Khng sinh no sau y khng hiu qu khi chng li Enterococcus
faecium khng vancomyciin?
a. Quinupristin/dalfopristin
b. Linezolid
c. Daptomycin
d. Tigecycline
e. Vancomycin
25. Phc khng sinh no c s dng cho bnh nhn nhim khun nng do Pseudomonas
aeruginosa?
a. Ceftazidime + tobramycin
b. Ceftriaxone + gentamicin
c. Piperacillin + rifampin
d. Ertapenem + amikacin
e. Ampicillin + tobramycin
26. Vancomycin c cho km vi ceftriaxone (trong iu tr theo kinh nghim (in the empiric
treatment of ) vim mng no do vi khun cp mc phi ti cng ng (community-acquired acute
bacterial meningitis) no trong cc vi khun sau
a. Neisseria meningitidis
b. Streptococcus pneumoniae
c. Staphylococcus aureus
e. Enterococcus faecium
27. Vi khun no sau y khng tt c cc khng sinh nhm -lactam bng cch sn xut ra mt
protein c bit l penicillin-binding protein lm cho tt c cc khng sinh -lactam khng gn
c trn chng.
a. Cc vi khun ng rut khng vancomycine (vancomycin-resistant enterococci)
b. Chng Escherichia coli sn xut -lactamase ph rng
c. Chng Enterobacter aerogenes sn xut
d. AmpC -lactamase
e. Staphylococcus aureus khng methicilline
f. Pseudomonas aeruginosa a khng thuc
28. Cc cht c ch -lactamase clavulanate, sulbactam, v tazobactam
c hiu qu c ch rt nhiu -lactamase ca cc nhm vi khun NGOI TR:
a. Pseudomonas aeruginosa
b. Bacteroides fragilis
c. Staphylococcus aureus
e. Proteus mirabilis
29. Ch iu tr c chp nhn cho ngi nhim Helicobacter pylori c th gm rt nhiu tc
nhn NGOI TR
a. Amoxicillin
b. Clarithromycin
c. Cefotaxime
d. Metronidazole
e. Bismuth subsalicylate
30. Tc nhn no sau y c hiu lc chng li vi khun gy ra vim phi khng in hnh?
a. Amoxicillin
b. Amoxicillin/clavulanate
c. Cefotaxime
d. Vancomycin
e. Azithromycin
205
31. Streptomycin c dng trong iu tr nhim khun c gy ra bi cc loi vi khun sau
NGOI TR
a. Enterococcus faecalis
b. Borrelia burgdorferi
c. Francisella tularensis
d. Mycobacterium tuberculosis
e. Brucella abortus
32. Vi khun no trong cc vi khun sau thng thay i kt cu chui peptide bn ca
peptidoglycan (the peptide side chain of peptidoglycan) khng li vancomycin ?
c. Enterococcus faecium
d. Streptococcus pneumoniae
e. Enterobacter aerogenes
33. Tt c cc tc nhn sau y c dng iu tr bnh nhn nhim lao NGOI TR:
a. pyrazinamide
b. isoniazid
c. rifampin
d. dapsone
e. ethambutol
34. Tc nhn no sau y c nh gi cao trong iu tr trong liu php iu tr nhim khun
ng tit niu khng bin chng cp tnh (an acute uncomplicated urinary tract
infection?)
a. Nitrofurantoin
b. Amoxicillin
c. Ampicillin
d. Ceftriaxone
e. Meropenem
35. Khng sinh no sau y hiu qu trong iu tr Helicobacter pylori,
Mycobacterium avium complex, Bordetella pertussis, mt s chng
Staphylococcus aureus v Streptococcus
pneumoniae?
a. Amoxicillin
b. Amoxicillin/clavulanate
c. Ceftriaxone
d. Doxycycline
e. Clarithromycin
36. Khng sinh no sau y khng thuc nhm aminoglycoside?
a. Streptomycin
b. Gentamicin
c. Tobramycin
d. Erythromycin
e. Amikacin
37. Tt c cc kt hp sau l ph hp vi vic iu tr vim phi bnh vin khi pht mun ngoi
tr
a. Cefepime + levofloxacin
b. Piperacillin/tazobactam + ceftazidime
c. Imipenem + ciprofl oxacin
d. Ceftazidime + tobramycin
e. Piperacillin/tazobactam + amikacin
38. Khng sinh no sau y c nh gi cao trong liu php iu tr nhim khun do Leptospira
interrogans?
a. Amoxicillin
b. Vancomycin
c. Linezolid
d. Streptomycin
e. Metronidazole
39. Cc phn ng bt li ph bin lin quan n penicilline bao gm nhng phn ng sau NGOI
TR:
a. Tiu chy
b. Pht ban
c. Sc phn v
d. Tn thng sn
e. Bnh huyt thanh
40. Clindamycin nhy cm tr cc nhim khun bi vi khun no sau y
?
a. Clostridium perfringens
b. Clostridium diffi cile
c. Clostridium tetani
d. Clostridium botulinum
e. Clostridium septicum
41. Cephalosporins th h 3
nn c s dng thn trong trong cc bnh nhim khun gy ra bi mt s vi khun nht nh loi
m cung cp cc nhim sc th AmpC -lactamase bi v s khng thuc c th pht trin trong sut
qu trnh iu tr. Chng no sau y khng phi l v d cho vi khun ni trn
a. Morganella spp.
b. Serratia spp.
c. Haemophilus spp.
d. Enterobacter spp.
e. Citrobacter spp.
42. Khng sinh no sau y hu dng trn lm sng chng li vi khun k kh?
207
a. Cefotetan
b. Cefotaxime
c. Cefuroxime
d. Cefazolin
e. Ceftazidime
43. Khng sinh no sau y km hiu qu nht i vi Pseudomonas
aeruginosa?
a. Imipenem
b. Meropenem
c. Ertapenem
d. Ceftazidime
e. Piperacillin
44. Khng sinh no sau y khng hiu qu khi chng li Legionella pneumophila?
a. Azithromycin
b. Levofloxacin
c. Moxifloxacin
d. Telithromycin
e. Piperacillin/tazobactam
45. Khng sinh no sau y dng cha bnh phong?
a. Isoniazid
b. Ethambutol
c. Clofazimine
d. Streptomycin
e. Amoxicillin/clavulanate
46. Iu no sau y c nh gi cao trong liu php iu tr cho bnh nhn vim ni tm mc
nhim khun trn van nguyn gc gy ra bi lin cu khun nhm viridans cc k khng penicilline
(Nng c ch ti thiu >0,5g /mL) bnh nhn nhim khun ni tm mc van bnh thng gy
bi
chng lin cu nhm viridans nhy cm cao vi penicillin
(minimum inhibitory
concentration _0.5 _g/mL)
?
a. Penicillin G
b. Ampicillin + streptomycin
c. Ceftriaxone
d. Ampicillin + gentamicin
e. Oxacillin + gentamicin
47. Tt c cc khng sinh sau y th hiu qu chng li Campylobacter jejuni
NGOI TR:
a. Erythromycin
b. Cefazolin
c. Azithromycin
d. Ciprofl oxacin
e. Doxycycline
48. Khng sinh no sau y khng c nh gi cao khi iu tr vim m t bo
a. Ceftazidime
b. Vancomycin
c. Oxacillin
d. Cefazolin
e. Clindamycin
49. c tnh chnh ca khng sinh ethambutol l
a. Pht ban
b. Nhim c gan
c. gout
d. Bnh huyt thanh
e. Vim dy thn kinh th gic
50. Liu php khng sinh ti u cho bnh nhn vim ni tm mc nhim khun bi Staphylococcus
aureus c th bao gm cc tc nhn sau y NGOI TR
a. Nafcillin
b. Rifampin
c. Linezolid
d. Vancomycin
e. Gentamicin
209
P N CHO CU HI CNG C
1. d. vancomycin. Ging nh cc -lactam vancomycin c ch tng hp vch t bo ca vi khun.
Tuy nhin, tuy nhin cu trc ca vancomycin khng c vng -lactam nn n khng thuc nhm
ny Khng sinh -lactam bao gm cc penicillin (v d, ampicillin),
cephalosporin (v d, ceftriaxone),
carbapenems (v d, meropenem), v
monobactams (v d, aztreonam).
2. c. ceftriaxone. Trong khi imipenem,
metronidazol, clindamycin, v
amoxicillin/clavulanate c tc dng tt trn vi khun k kh th ceftriaxone t c tc dng nn nhm
vi khun ny
3. a. aztreonam. Tt c cc khng sinh -lactam nn trnh dng nhng ngi c tin s d ng vi
Penicilline (v d, m ay hoc sc phn v) ngoi tr azetreonam. Azetronam c rt t phn ng d
ng cho vi cc -lactam khc.
4. b. cefazolin. Nhim khun ng rut thng thng c iu tr vi khng sinh nhm
penicilline (V d, penicillin, ampicillin, hoc piperacillin) kt hp vi mt aminoglycosid
(gentamicin hoc streptomycin). Vancomycin thngch c s dng cho cc chng khng
penicillin. Tt c vi khun ng rut u khng vi cephalosporin.
5. e. ciprofloxacin. Ciprofloxacin l khng sinh nhm quinolone ph bin nht, lun sn c v c tc
dng tt ln Pseudomonas aeruginosa.
6. c. Bacteroides fragilis. Rifampin c s dng kt hp vi mt penicillin khng t cu hoc
vancomycin iu tr nhim khun do ghp c quan lin quan n t cu
N c s dng nh d phng khi
tip xc vi Neisseria meningitidis v
l mt trong nhng thuc chnh c s dng iu tr nhim Mycobacterium tuberculosis.
N khng c s dng trong iu tr
cc nhim khun k kh, chng hn nh nhng ngi b nhim khun do B. fragilis.
7. a. Treponema pallidum. Nhim trng
do T. pallidum, gy gianh mai thng c iu tr ch bng Penicilline n cn. Nhim trng
Brucella thng c iu tr vi doxycycline, rifampin, gentamicin, hoc streptomycin. Nhim
khun Psedomonas aeruginosa nghim trng thng c iu tr vi 2 khng sinh. S nhim trng
Mycobacterium
(bnh lao) v Helicobacter pylori(Vim lot d dy t trng) thng c iu tr vi phc c
nhiu khng sinh.
8. b. isoniazid. Mc d isoniazid
l mt phn ca phc khng sinh ci li
dng iu tr Mycobacterium tuberculosis, nhng n khng c hiu lc i vi
Mycobacterium avium phc hp (Mycobacterium avium complex). clarithromycin, ethambutol,
rifabutin,
v ciprofloxacin c dng iu tr
M. avium phc hp.
9. d. metronidazole.Nhim trng do Clostridium difficile c iu tr bng metronidazole hoc
vancomycin. Clindamycin,imipenem, penicillin, v piperacilli /tazobactam khng c tc dng
chng li vi sinh vt ny. c bit Clindamycin c th tr bnh do C. difficile
10. c. meropenem. Cc vi khun sn xut c -lactamase ph rng khng vi hu ht cc
khnh sinh nhm -lactam ngoi tr carbapenems. V vy trong cc khng sinh c lit k trn
th ch c meropenem l ng tnh cy chng li cc vi khun ny
11. a. gentamicin. Aztreonam, imipenem,
v ampicillin u l khng sinh nhm -lactam hot ng thng qua vic c ch penicilline-blinding
protein, mt protein rt quan trng i vi vic tng hp mng t bo vi khun. Tng t
vancomycine hot ng bng cch ngn vic gn cc chui peptidoglycan ca vi khun dn n c
ch tng hp mng t bo. Trong khi Gentamicin hot ng theo mt hng khc, c ch ARN
ribosome ca vi khun.
12. e. Staphylococcus aureus. Mc d penicilline vn thng c ung iu tr nhim
Treponema pallidum
(Giang mai), Streptococcus pyogenes
(Vim hng do lin cu), Clostridium
perfringens (k kh hoi t), v
Neisseria meningitidis (lu),
nhng n khng c tc dng iu tr bnh nhim trng do Staphylococcus aureus.
13. b. Clostridium cilediffi. Vancomycin
ch c hot tnh chng li vi khun Gram dng. Bordetella pertussis, Pseudomonas
aeruginosa, Haemophilus influenzae,
v Enterobacter aerogenes u l vi khun gram m
vi khun.
14. c. ampicillin. mt t l ng k cc chng Haemophilus influenzae nay
sn xut -lactamase ph hoi
ampicillin v amoxicillin. Tuy nhin -lactamase, c ch bi cc sn phm
thng mi c sn cc cht c ch -lactamase, v vy amoxicillin/clavulanate
c hiu qu chng li cc chng sn xut -lactamase. Cefuroxim v cefotaxim l
khng vi s phn hy ca -lactamase nn cng c hiu qu chng li cc chng ny.
doxycycline cng c hiu qu chng li hu ht cc chng Haemophilus influenzae .
15. b. azithromycin. cc Quinolone, chng hn nh ciprofloxacin v gemifloxacin,
nn c s dng thn trng tr s sinh
v tr em di 18 tui tui v n c lin quan n tn thng gan v sn trn ng vt tui thnh
nin. Tetracycline v doxycycline thng nn trnh tr em
tr hn 8 tui. azithromycin l an ton s dng tr em.
16. d. Cc cn bn mt (biliary sludging) l tc dng khng mong mun tng i ph bin i vi
cc khng sinh nhm
aminoglycoside. Cc tc dng khng mong mun nh suy gim gim chc nng thn v c tnh
tin nh.
211
cn bn mt (biliary sludging) c lin quan
vic s dng ceftriaxone.
17. a. Mycobacterium tuberculosis. Pyrazinamide l mt thnh phn ct li ca phc 4 loi thuc
c bn iu tr
: isoniazid, rifampin,
pyrazinamide v ethambutol.
N c hot tnh khng ng k ln Mycobacterium avium complex, Mycobacterium leprae, hoc
cc vi sinh vt khng thuc h Mycobacterium (nonmycobacterial organisms.)
18. e. ceftriaxone. Chlamydia trachomatis,
gy chlamydia(mt bnh ng sinh dc), d dng c iu tr bng doxycycline, azithromycin,
ofloxacin, v levofloxacin nhng khng li Ceftriaxone. Ceftriaxone c s dng iu tr cc
bnh ly truyn qua ng tnh dc khc nh bnh lu, gy ra bi Neisseria
gonorrhoeae.
19. e. HACEK sinh vt. cc HACEK
sinh vt (parainfluenzae Haemophilus,
Aggretibacter aphrophilus, Aggretibacter
actinomycetemcomitans, Cardiobacterium
hominis, Eikenella Corrdens, v Kingella kingae) l vi khun m gram- v do khng vi
vancomycin.
20. c. tetracycline. Tetracycline lin kt vi tiu n v 30S ca ribosome vi khun
v ngn nga s kt hp gia tRNA
vi mt axit amin v tr Loaded . isoniazid c ch s tng hp acid mycolic.
Vancomycin c ch tng hp vch t bo.
Levofloxacin c ch topoisomerases.
Trimethoprim-sulfamethoxazole c ch s tng hp ca tetrahydrofolate -mt tin cht cn thit
cho vic
sn xut ca DNA.
21. b. clindamycin. Clindamycin hot ng chng li nhiu vi khun Gram dng v vi khun k
kh nhng khng c tc dng ln xon khun nh Borrelia burgdorferi. Loi vi khun ny, nguyn
nhn gy bnh Lyme c iu tr d dng vi doxycyline, amoxicillin, cefuroxime, ceftriaxone
cng nh l erythromycin v penicillin.
22. d. aeruginosa Pseudomonas. Doxycycline hot ng tuyt vi chng li
interrogans Leptospira, Brucella abortus,
Chlamydia trachomatis, v Rickettsia
rickettsii nhng khng c tc dng ln P.aeruginosa.
23. c. rifampin. mc tiu Rifampin l
RNA polymerase ca vi khun, trong khi cefotetan ngn chn s tng hp thnh t bo,amikacin v
zithromycin c ch tc ng l ribosome ca vi khun, daptomycin to thnh mt knh ion dn
in trn mng t bo ca vi khun.
24. e. vancomycin. Kim tra li iu so v bn s thy. im mu cht l
quinupristin / dalfopristin, linezolid,
daptomycin, v tigecycline tng c hiu qu chng li nhiu chng Enterococcus faecium khng
vancomycin
. Lu :Enterococcus faecalis
c chng khng vi quinupristin /
dalfopristin.
25. a. ceftazidime+tobramycin. c
ceftazidime v tobramycin c
hot tnh khng pseudomonas
v cho php c 2 khng sinh chng li c Psedomonas aeruginosa. Ngc li,
mi phc cn li cha ch c mt tc nhn duy nht c th chng li vi khun ny. Ceftriaxone,
rifampin, ertapenem, v ampicillin t hoc khng c hiu lc chng pseudomonas(
antipseudomonal).
26. b. Streptococcus pneumoniae. Mt s
cc chng Streptococcus pneumoniae
khng ceftriaxone, do trn lm sng vancomycin c thm vo. Neisseria meningitidis v
Haemophilus influenzae s bao ph y v n c ceftriaxone. Vancomycin c nh gia cao
khi chng li Staphylococcus aureus v Staphylococcus epidermidis, nhng nhng vi khun ny
him khi gy vim mng no m cp cng ng
27. d. Staphylococcus aureus khng methicillin (MRSA). MRSA sn xut 1 protein PBP2, mt
Penicilline-Blinding protein (PBP) loi Protein ny s khng b bt k khng sinh -lactam no
nhn ra. V l do ny,MRSA khng th c iu tr bi cc tc nhn ny
28. a. Pseudomonas. aeruginosa . S kt hp gia clavulanate, sulbactam, hoc tazobactam vi
penicillin tng cng kh nng chng li vi khun k kh nh Bacteroides fragilis; nhiu vi khun
gram m nh Haemophilus uenzaeinfl v
Proteus mirabilis; v mt s t cu
nh Staphylococcus aureus.
Tuy nhin, tng cng khng ng k hot ng chng li Pseudomonas aeruginosa.
29. c. cefotaxime. Cc phc s dng iu tr nhim trng Helicobacter pylori bao gm
amoxicillin + clarithromycin thuc c ch bm proton; metronidazole
+ clarithromycin + thuc c ch bm proton; v bismuth subsalicylate +
metronidazole + tetracycline + thuc c ch bm proton. Cefotaxime khng c s dng iu
tr vi khun ny.
30. e. azithromycin. Cc vi khun ph bin
gy vim phi khng in hnh l Mycoplasma pneumoniae, Chlamydophila
pneumoniae v Legionella pneumophila.
Thuc khng sinh nhm vch t bo,
nh -lactams (amoxicillin, amoxicillin /
clavulanate, v cefotaxime) v
vancomycin, khng c hiu qu chng li
cc vi khun ny. Tuy nhin cc vi khun ny nhy cm vi cc macrolid, chng hn nh
azithromycin.
213
31. b. Borrelia burgdorferi. streptomycin
c s dng iu tr nhim khun ng rut, tularemia, bnh lao, v
brucella. N khng phi l mt thnh phn ca phc c ngh cho bnh Lyme
(Borrelia burgdorferi).
32. c. Enterococcus faecium. Mt s E. faecium
thay d-alanined-lactate
bng ui d-alanined-alanine
ca chui peptide capeptidoglycan
. iu ny ngn cn rng vic gn kt ca Vancomycin, dn n vic khng thuc
Mc d gn cng y pht hin c mt s chng Staphylococcus aureus cng c kh nng ny.
Kiu khng vancomycin l kiu ph bin nht tn ti cc vi khun ng rut .
33. d. dapsone. Isoniazid, Rifampin, pyrazinamid, v ethambutol thng
dng iu tr bnh lao. Dapsone c s dng iu tr bnh phong.
34. a. nitrofurantoin. nitrofurantoin hoc
trimethoprim-sulfamethoxazole l
khng sinh ngh cho cc nhim khun ng tit niu khng bin chng.
35. e. clarithromycin. clarithromycin thng c dng iu tr nhim trng
do Helicobacter pylori, Mycobacterium
avium phc tp, v Bordetella pertussi.. Ngoi ra, mt s chng
Staphylococcus aureus v Streptococcus
pneumoniae vn cn nhy cm vi
n. Amoxicillin khng c hot tnh chng li Staphylococcus aureus, M. avium complex, hoc
B.pertussis. Amoxicillin/ clavulanate khng c s dng iu tr nhim trng gy ra bi M.
avium complex hoc B. pertussis. Ceftriaxone khng c s dng iu tr nhim trng do vi
khun H. pylori, M. avium complex, hoc B. pertussis. Doxycycline khng c thng xuyn s
dng iu tr nhim trng gy ra bi M. avium complex hoc Staphylococcus aureus.
36. d. erythromycin. Erythromycin l mt
macrolide, trong khi streptomycin,
gentamicin, tobramycin, v amikacin
u thuc nhm aminoglycosid.
37. b. piperacillin / tazobactam + ceftazidime.
ngh iu tr cho vin phi khi pht mun bnh vin
bao gm hai tc nhn vi hot tnh
chng li vi khun gram-
. Tc nhn u tin kinh phi l mt
antipseudomonal cephalosporin, antipseudomonal carbapenem, hoc piperacillin / tazobactam. Tc
nhn th hai l mt aminoglycoside hoc mt quinolone antipseudomonal. Nu c nghi ng v
nhim MRSA, th nn b xung linezolid hoc vancomycin nn.
38. a. amoxicillin. Amoxicillin thch hp
iu tr cho bnh nhim trng xon khun nh.Vancomycin, linezolid, streptomycin,
v metronidazole khng c khuyn khch cho cc bnh nhim trng ny.
39. d. Tn thng sn. Penicillin gy tc dng khng mong mun: tiu chy, pht ban, sc phn v
v bnh huyt thanh.
Tn thng sn xy ra ng vt cha trng thnh khi tip xc vi quinolone.
40. b. Clostridium difficile. Vic s dng
clindamycin lin quan n s pht trin ca tiu chy v Vim i trng do C. difficile.
41. c. Haemophilus spp. Trong khi , Morganella, Serratia, Enterobacter, Citrobacter (V
Providencia) spp. Sn xut mt cht cm ng chromosomally m ha cho AmpC -lactamase c
th dn n tht bi trong iu tr vi cephalosporin th h ba, Haemophilus spp.
khng sn xut ny -lactamase
42. a. cefotetan. Trong cc cephalosporin sn c, ch cefotetan v cefoxitin c hot tnh chng li
cc vi khun k kh.
43. c. ertapenem. Khng ging nh cc carbapenems imipenem v meropenem,
ertapenem c hot tnh antipseudomonal tng i yu. Ceftazidime v piperacillin c hot tnh
antipseudomonal mnh.
44. e. piperacillin / tazobactam. Cc First-Line cho cc nhim khun do Legionella
pneumophila bao gm azithromycin,
levofloxacin, v moxifloxacin. Telithromycin l mt second-line.
Piperacillin / tazobactam khng c hot tnh chng vi khun ny, c l v n khng xm nhp vo
c cc i thc bo, ni m cc vi khun Legionella c tr.
45. c. clofazimine. Phc khng sinh khuyn co iu tr
bnh phong l dapsone + rifampin c th km theo clofazimine. Isoniazid, ethambutol, v
streptomycin c s dng
iu tr lao nhng khng c hot tnh chng li Mycobacterium leprae.
Amoxicillin / clavulanate cng khng
c hot ng chng vi khun ny.
46. d. ampicillin + gentamicin. Ampicillin
+ gentamicin hoc penicillin G
+ gentamicin l pht khng sinh c ngh cho bnh nhn vim ni tm mc nhim khun
bm sinh gy ra bi cc chng khng penicillin mnh ca
nhm Streptococcus viridans. Penixilin
G hoc ceftriaxone c nh gi cao trong cc trng hp nhim khun gy ra bi cc chng vi
khun nhy cm vi Penicilline. Oxacillin s c s dng cho cc trng hp vim ni tm mc
gy ra bi cc chng Staphylococcus aureus nhy cm. Ampicillin + streptomycin c th c s
dng iu tr vim ni tm mc gy ra bi cc chng enterococci nhy cm tr loi Virridans
nhm Streptococci
47. b. cefazolin. Cefazolin l khng hiu qu trong iu tr tiu chy bnh nhn nhim
Campylobacter jejuni. erythromycin, azithromycin, v ciprofloxacin l nhng first-line cho nhng
trng hp nhim trng ny. Doxycycline ch dng d phng.
48. a. ceftazidime. Cc liu php c nh gi cao trong iu tr vim m t bo bao gm cc tc
nhn hot ng mnh chng li cu khun Gram dng ( nguyn nhn hu ht cc bnh nhim
215
trng). Vancomycin, oxacillin, cefazolin, v clindamycin tng c nh gi cao trong hot tnh
chng li cc cu khun Gram dng nhng ceftazidime c t hot tnh chng li cc vi khun ny.
49. e. vim dy thn kinh th gic. S dng ethambutol gn lin vi s pht trin
ca vim dy thn kinh th gic, c th dn n gim th lc v m mu -xanh(Khng phn bit
c 2 mu ny) 50. c. linezolid. Liu php khng sinh c ngh cho bnh nhn vim ni tm
mc do t van tim gi gy ra bi
Staphylococcus aureus nhy cm vi methicillin l mt penicilin c hiu qu antistaphylococcal
(khng t cu)
(Nafcillin hoc oxacillin)+ rifampin+
gentamicin. Liu php c khuyn co cho S. aureus khng methicillin
l vancomycin + rifampin +
gentamicin. Linezolid l mt khng sinh kim khun v s khng c hiu qu tt trong iu tr vim
ni tm mc nhim khun.
PHN VI. PH LC
Ph lc 1. Liu khng sinh ngi trng thnh

Th.S-DSLng Th Hi Vn-khoa dc bv Nhn Dn Gia nh Tp H Ch Minh
TC NHN LIU THNG THNG NGI TRNG THNH

C CHC NNG THN BNH THNG
Cc penicillin t nhin
Penicillin G 2-30 triu n v/ngy chia nhiu liu IV/IM mi 4-6 gi

(Lu : ng IM khng nn c dng cho nng > 10 triu
n v/mL)
Penicillin V 125-500 mg PO mi 6-8 gi
Cc penicillin khng t cu
Nafcillin 0,5-2 g IV/IM mi 4-6 gi
Oxacillin Nhim trng nh n trung bnh: 250-500 mg IV/IM mi 4-6 gi

Nhim trng nng: 1-2 g IV mi 4-6 gi
Dicloxacillin 125-500 mg PO mi 6 gi
Cc aminopenicillin
Ampicillin Nhim trng nh n trung bnh: 250-1000 mg PO, IM hoc IV

mi 6 gi
Nhim trng nng: 150-200 mg/kg/ngy IV/IM chia nhiu liu mi
3-4 gi (liu thng thng: 2 g IV mi 4 gi)
Amoxicillin 250-500 mg PO mi 8 gi hoc 500-875 mg PO mi 12 gi (1 g

PO mi 8 gi i vi vim phi do Streptococcus pneumoniae)
Aminopenicillin + cht c ch -lactamase
Ampicillin-sulbactam 1,5-3 g IV/IM mi 6 gi (ti a: 12 g/ngy)
Amoxicillin-clavulanate 250 mg amoxicillin/125 mg clavulanate, 1 vin PO mi 8 gi

500 mg amoxicillin/125 mg clavulanate, 1 vin PO mi 8-12 gi
hoc
217
875 mg amoxicillin/125 mg clavulanate, 1 vin PO mi 12 gi
Amoxicillin-clavulanate 1000 mg amoxicillin/62,5 mg clavulanate, 2 vin PO mi 12 gi

phng thch ko di (s dng dng phng thch ko di i vi vim phi do S.
pneumoniae)
Penicillin ph rng
Piperacillin 3-4 g IV/IM mi 4-6 gi (ti a: 24 g/ngy)

(Khng nn dng ng IM i vi liu vt qu 3 g)
Penicillin ph rng + cht c ch -lactamase
Piperacillin-tazobactam 3,375 g mi 6 gi hoc 4,5 g mi 8 gi

(4,5 g IV mi 6 gi i vi Pseudomonas aeruginosa)
Ticarcillin-clavulanate 3,1 g IV mi 4-6 gi
Cc cephalosporin th h 1
Cefazolin 0,5-2 g IV/IM mi 6-8 gi (ti a: 12 g/ngy)
Cefadroxil 1-2 g PO chia nhiu liu mi 12-24 gi
Cephalexin 0,25-1 g PO mi 6 gi (ti a: 4 g/ngy)
Cefotetan 1-3 g IV/IM mi 12 gi (ti a: 6 g/ngy)
Cefoxitin 1-2 g IV/IM mi 4-6 gi hoc 1-2 g IV mi 4 gi (ti a: 12

g/ngy)
Cefuroxime 0,75-1,5 g IV/IM mi 8 gi

Vim mng no: 3 g IV mi 8 gi
Cefuroxime axetil 250-500 mg PO mi 12 gi
Cefprozil 250 mg PO mi 12 gi hoc 500 mg PO mi 12-24 gi
Cefaclor 250-500 mg PO mi 8 gi
Loracarbef 200-400 mg PO mi 12 gi
Cefotaxime 1 g IV mi 8-12 gi n 2 g IV mi 4 gi
Ceftazidime 1-2 g IV mi 8-12 gi
Ceftriaxone 1-2 g IV mi 12-24 gi
Cefdinir 300 mg PO mi 12 gi hoc 600 mg PO mi 24 gi
Cefditoren 200-400 mg PO mi 12 gi
Cefpodoxime 100-400 mg PO mi 12 gi
Ceftibuten 400 mg PO mi 24 gi
Cefixime 400 mg/ngy PO chia nhiu liu mi 12-24 gi
Cefepime 1-2 g IV mi 8-12 gi
Ceftaroline 600 mg IV mi 12 gi
Cc carbapenem
Imipenem/cilastatin 0,5-1 g (imipenem) IV mi 6-8 gi (ti a: 50 mg (imipenem)/kg

hoc 4 g (imipenem)/ngy, ty theo liu no thp hn) hoc 500-
750 mg IM mi 12 gi
Meropenem 0,5-2 g IV mi 8 gi
Ertapenem 1 g IV/IM mi 24 gi
Doripenem 0,5 g IV mi 8 gi
Monobactam
Aztreonam 1-2 g IV/IM mi 8-12 gi cho ti 2 g mi 6-8 gi (ti a: 8 g/ngy)
Cc glycopeptide
Vancomycin 15 mg/kg IV mi 12 gi
0,5-2 g/ngy PO chia nhiu liu mi 6-8 gi (Khng nn dng
ng ung i vi cc nhim trng ton thn; liu nn c iu
chnh da trn nng huyt thanh khi cn)
Telavancin 10 mg/kg IV mi 24 gi
219
Daptomycin 4-6 mg/kg IV mi 24 gi
Colistin (colistimethate) 2,5-5 mg/kg IM/IV chia 2-4 liu
Cc rifamycin
Rifampin Tr liu lao: 10 mg/kg PO/IV mi 24 gi (ti a: 600 mg/ngy)

Phi hp trong nhim khun t cu: 300-600 mg PO/IV mi 8-12
gi vi cc khng sinh khc.
Rifabutin Tr liu Mycobacterium avium-intracellulare complex: Giai on

u: 5 mg/kg PO mi 24 gi (ti a: 300 mg/ngy); giai on hai: 5
mg/kg PO/ngy hoc 2 ln/tun; c th cn iu chnh liu bnh
nhn ang dng ng thi vi cht c ch protease
Rifapentine Tr liu lao: 600 mg PO x 2 ln/tun (mi 72 gi) trong 2 thng u

iu tr, sau mt ln/tun
Rifaximin 200 mg PO mi 8 gi
Cc aminoglycoside (Liu nn c iu chnh da trn nng nh v nng y)
Streptomycin 1-2 g/ngy IM chia nhiu liu mi 6
Gentamicin Liu ti 2 mg/kg IV/IM, sau 5,1 mg/kg/day IV/IM chia nhiu
liu mi 8 gi;
Liu mt ln mi ngy: 4-7 mg/kg IV mi 24 gi
Tobramycin Liu ti 2 mg/kg IV, sau 5,1 mg/kg/ngy IV chia nhiu liu mi
8 gi;
Liu mt ln mi ngy: 15 mg/kg IV mi 24 gi
Amikacin 15 mg/kg IV chia nhiu liu mi 8-12 gi;

Liu mt ln mi ngy: 15 mg/kg IV mi 24 gi
Cc macrolide v ketolide
Erythromycin Dng base, mui estolate, mui stearate: 250-500 mg PO mi 6-12

gi (ti a: 4 g/ngy)
Dng mui ethylsuccinate: 400-800 mg PO mi 6 gi (ti a 3,2
g/ngy)
Dng lactobionate: 15-20 mg/kg/ngy IV chia nhiu liu mi 6 gi
hoc 0,5-1 g IV mi 6 gi (ti a: 4 g/ngy)
Azithromycin Mt liu ti duy nht 500 mg PO vo ngy 1, sau mt liu 250

mg/ngy vo ngy 2-5 hoc liu tng cng 500 mg/ngy trong 3
ngy.
Dng hn dch phng thch ko di: mt liu duy nht 2 g PO
500 mg IV mi 24 gi
Clarithromycin 250-500 mg PO mi 12 gi
Dng phng thch ko di: 1 g PO mi 24 gi
Telithromycin 800 mg PO mi 24 gi
Cc tetracycline v glycylcycline
Tetracycline 250-500 mg PO mi 6 gi
Doxycycline 100-200 mg/ngy PO/IV chia nhiu liu mi 12-24 gi
Minocycline Liu u tin 200 mg PO, sau 100 mg PO mi 12 gi
Tigecycline Liu u tin 100 mg IV, sau 50 mg IV mi 12 gi
Chloramphenicol 50-100 mg/kg/ngy chia nhiu liu PO/IV mi 6 gi (ti a: 4

g/ngy)
Clindamycin 150-450 mg PO mi 6-8 gi (ti a: 1,8 g/ngy)

0,6-2,7 g IV/IM chia nhiu liu mi 6-12 gi
Streptogramin
Quinupristin/dalfopristin 7,5 mg/kg IV mi 8-12 gi
Linezolid 600 mg PO/IV mi 12 gi
Nitrofurantoin Furadantin, Macrodantin: 50-100 mg PO mi 6 gi

Macrobid: 100 mg mi 12 gi
Trimethoprim- 1 vin DS PO mi 12 gi
sulfamethoxazole 8-10 mg (trimethoprim)/kg/ngy IV chia nhiu liu mi 6-12 gi
cho ti 15-20 mg (trimethoprim)/kg/ngy chia nhiu liu mi 6-8
gi
Cc quinolon
Ofloxacin 200-400 mg PO mi 12 gi
Ciprofloxacin 250-750 mg PO mi 12 gi
221
Cipro XR 500-1000 mg PO mi 24 gi
200-400 mg IV mi 8-12 gi
Levofloxacin 250-750 mg PO/IV mi 24 gi
Moxifloxacin 400 mg PO/IV mi 24 gi
Gemifloxacin 320 mg mi 24 gi
Metronidazole 250-750 mg PO/IV mi 6-8 gi
Cc tc nhn khng lao (Liu c khuyn co cho ch mt ln mt ngy)
Isoniazid 5 mg/kg PO/IM mi 24 gi (ti a: 300 mg/ngy)
Rifampin Tr liu lao: 10 mg/kg PO/IV mi 24 gi (ti a: 600 mg/ngy)
Pyrazinamide 25-30 mg/kg/ngy PO mi 24 gi (ti a: 2 g/ngy)
Ethambutol 15-25 mg/kg/ngy PO mi 24 gi
c chp thun bi Gilbert DN, Moellering RC Jr, Eliopoulos GM, et al. The Sanford Guide to
Antimicrobial Therapy, 2011. 41st ed. Sperryville, VA: Antimicrobial Therapy, Inc.; 2011; Rose
BD. UptoDate. Available at: http://www.uptodate.com. Accessed February 2011; Micromedex
Healthcare Series (http://www.micromedex.com). Greenwood Village, CO: Thomson Micromedex;
2006; Clinical Pharmacology. Tampa, FL: Gold Standard, Inc., 2006. Available at:
http://www.clinicalpharmacology.com. Accessed September 2006; American Society of Health-
System Pharmacists. AHFS Drug Information 2011. Bethesda, MD: American Society of Health-
System Pharmacists; 2011
Ph lc 2: Liu khng sinh s dng tr em
Tc nhn Liu thng dng cho tr s sinh c chc nng thn bnh thng
Penicillin t nhin
Penicillin G Tr nh nhi v tr nh
- Nhim trng nh-trung bnh: 25.000-50.000 n v/kg/ngy tim tnh
mch hoc tim bp/ chia nhiu ln, mi 4 gi/ln
- Nhim trng nng: 250.000-400.000 n v/kg/ngy/ tim tnh mch hoc
tim bp/ chia nhiu ln, mi 4-6 gi/ln. Ti a 24 triu n v/ngy
Penicillin V - Tr nh di 12 tui: 25-50 mg/kg/day PO, chia nhiu ln mi 6-8
gi/ln.
- Tr trn 12 tui: 125-500 mg PO mi 6-8 gi
Penicillin tr Staphylococcal
Nafcillin Tr nh nhi v tr nh
- Nhim trng nh-trung bnh: 50-100mg/kg/ngy IV hoc IM, chia lm
nhiu ln, mi 6 gi/ln
- Nhim trng nng: 100-200 mg/kg/ngy IV hoc IM, chia lm nhiu ln,
mi 4-6 gi/ln, ti a 12g/ngy
Oxacillin - Nhim trng nh-va: 100-150 mg/kg/ngy IV hoc IM, chia lm nhiu
ln, mi 6 gi/ln, ti a 4g/ngy
- Nhim trng nng: 150-200 mg/kg/ngy IV hoc IM, chia lm nhiu ln,
mi 6 gi/ln, ti a 12g/ngy.
Dicloxacillin - Tr nh < 40 kg: 24-50 mg/kg/ngy PO mi 6 gi.
- Tr > 40 kg: 125-500 mg PO mi 6 gi, ti a 2g/ngy.
Nhm Aminopenicillin
Ampicillin Tr nh nhi v tr nh:

- 100-400 mg/kg/ngy IV hoc IM, chia lm nhiu ln, mi 6 gi/ln, ti a
12g/ngy.
- 50-100 mg/kg/ ngy PO, chia lm nhiu ln, mi 6 gi/ln, ti a 2-
4g/ngy.
Amoxicillin - Tr nh nhi < =3 thng tui: 20-30 mg/kg/ngy PO, chia lm nhiu ln,
mi 12 gi/ln
- Tr nh nhi v tr nh > 3 thng tui: 20-90mg/kg/ngy PO, chia lm
nhiu ln, mi 8-12 gi/ln.
223
Nhm Aminopenicillin + cht c ch -lactamase
Ampicillin+Sulba - Tr nh nhi > 1 thng tui: 100-300 mg (tnh theo ampicillin)/kg/ngy IV

ctam hoc IM, chia lm nhiu ln, mi 6 gi/ln
- Tr em > 1 tui: 100-400 mg (tnh theo ampicillin)/kg/ngy IV hoc IM,
chia lm nhiu ln, mi 6 gi/ln, ti a 8g ampicillin/ngy
Amoxicillin + - Tr<3 thng tui: 30 mg (tnh theo amoxicillin)/kg/ngy PO chia lm
clavulanat nhiu ln, mi 12 gi/ln, s dng 125mg/5ml hn dch.
- Tr< 40kg: 20-40 mg (tnh theo amoxicillin)/kg/ngy PO chia lm nhiu
ln, mi 8 gi/ln, hoc 25-45mg (tnh theo amoxicillin)/kg/ngy, s dng
200mg/5ml hoc 400mg/5ml hn dch, hoc 200mg hoc 400 mg (tnh theo
amoxicillin) dang vin nhai c.(Vi trng hp vim tai gia cp tnh do
Streptococcus pneumoniae a khng: 90 mg (tnh theo
amoxicillin)/kg/ngy chia liu mi 12 gi, use 7:1 BID formulation or
Augmentin ES-600). Tr <40 kg khng nn cho s dng vin nn bao film
250mg.
Nhm Penicillin ph rng
Piperacillin Tr nh nhi v tr nh: 200-300 mg/kg/ngy IV hoc IM, chia liu mi 4-6
gi, ti a 24g/ngy.
Penicillin ph
rng + cht c
ch -lactamase
Piperacilin + - Hiu qu v tnh an ton tr < 12 tui cha c chng minh
tazobactam - Tr nh nhi v tr nh: 200-300 mg/kg/ngy chia liu mi 6-8 gi.
Ticarcillin + - Tr nh nhi v tr nh > 3 thng tui: 200-300mg (tnh theo
clavulanate ticarcillin)/kg/ngy IV chia liu 4-6 gi, ti a 18-24 gi/ngy.
Nhm Cephalosporin th h 1
Cefazolin Tr nh nhi v tr nh: 25-100 mg/kg/ngy IV hoc IM, chia liu mi 4-6
gi, ti a 6g/ngy.
Cefadroxil Tr nh nhi v tr nh: 30mg/kg/ngy PO, chia liu mi 12 gi, ti a
2g/ngy.
Cephalexin Tr>1 tui: 25-100 mg/kg/ngy PO, chia liu mi 6-8 gi, ti a 4g/ngy.
Cefotetan Tr nh: 40-80mg/kg/ngy IV hoc IM, chia liu mi 12 gi, ti a 6g/ngy

Cefoxitin Tr nh nhi > 3 thng tui v tr nh: 80-160 mg/kg/ngy IV hoc IM chia
liu mi 4-6 gi, ti a 12g/ngy
Cefuroxim Tr nh > 3 thng tui-12 tui: 75-150 mg/kg/ngy IV hoc IM chia liu
mi 8 gi, n 200-240 mg/kg/ngy chia liu mi 6-8 gi, ti a 9g/ngy.
Tr nh >13 tui: 0.75-1.5 g IV hoc IM mi 8 gi
Cefuroxim axetil - Tr >=3 thng tui-12 tui:

hn dch 20-30mg/kg/ngy PO, chia liu mi 12 gi, ti a 1g/ngy
Dng vin nn: 125-250mg PO mi 12 gi
- Tr> 13 250-500 mg PO mi 12 gi
Cefprozil - Tr >6 thng -12 tui: 7.6mg/kg PO mi 12 gi hoc 20mg/kg PO mi 24
gi, ti a 1g/ngy
- Tr> 12 tui: 250-500 mg PO mi 12 gi hoc 500 mg PO mi 24 gi.
Cefclor Tr nh nhi >1 thng tui v tr nh: 20-40 mg/kg/ngy PO chia liu mi 8-
12 gi, ti a 1g/ngy.
Loracarbef - Tr:6 thng tui - 12 tui: 15-30 mg/kg/ngy PO, chia liu mi 12 gi.
- Tr> 12 tui: 200-400 mg PO mi 12 gi.
Cefotaxime - Tr: 1 thng -12 tui: <50kg: 75-100mg/ kg/ngy n 150-300

mg/kg/ngy, chia liu mi 6-8 gi.
- Tr> 12 tui: 1-2 g IV mi 6-8 gi
Cefazidime - Tr: 1 thng -12 tui: <50kg: 100-150mg/ kg/ngy, chia liu mi 8 gi, ti
a 6g/ngy
- Tr> 12 tui: 1-2 g IV mi 6-8 gi
Ceftriaxone Tr nh nhi v tr nh: 50-100 mg/kg/ngy IV hoc IM, chia liu mi 12-24
gi, ti a 4g/ngy.
Cefdinir - Tr: 6 thng-12 tui: 14 mg/kg/ngy PO, chia liu mi 12-24 gi, ti a
600mg/ngy.
- Tr > 12 tui: 300 mg PO mi 12 gi hoc 600 mg PO mi 24 gi
Cefditoren Tr >= 12 tui: 200-400 mg PO mi 12 gi
Cefpodoxime - Tr: 2 thng tui-12 tui: 10 mg/kg/ngy PO, chia liu mi 12 gi, ti a
200 -400 mg/ngy
- Tr > 12 tui: 100-400 mgPO mi 12 gi
Ceftibuten - Tr < 12 tui: 9mg/kg PO mi 24 gi, ti a 400mg/ngy
- Tr>=12 tui: 400 mg PO mi 24 gi
Cefixime Tr nh nhi v tr nh: 8mg/kg/ngy, chia liu mi 12-24 gi, ti a
400/ngy
Cefepime Tr: 2 thng-16 tui: <40 kg: 50 mg/kg IV hoc IM mi 8-12 gi

Nhm Carbapenem
225
Imipenem/cilastat - Tr nh nhi t 4 tun-3 thng tui: 100mg/kg/ngy IV, chia liu mi 6 gi
in - Tr nh nhi > 3 thng tui v tr nh: 60-100 mg/kg/ngy IV, chia liu
mi 6 gi, ti a 4 g/ngy.
Meropenem - Tr> 3 thng tui (<50kg): 10-40 mg/kg/ngy IV, chia liu mi 8 gi, ti
a 1-2g mi 8 gi
- Tr > 50kg: 1-2 g IV mi 8 gi
Ertapenem Tr: 3 thng-12 tui: 30 mg/kg/ngy IV hoc IM, chia liu mi 12 gi, ti
a 1g/ngy
Nhm Monobactam
Aztreonam Tr>1 thng tui: 30 mg/kg IV hoc IM mi 6-8 gi n 50/mg/kg IV mi

6-8 gi, ti a 120 mg/kg/ngy hoc 8g/ngy
Nhm Glycopeptide
Vancomycin Tr nh nhi > 1 thng tui v tr nh: 40-60 mg/kg/ngy IV, chia liu mi
6-8 gi, ti a 2g/ngy
Colistin 2.5-5 mg/kg/ngy IV hoc IM chia lm 2-4 ln
(colistimethate)
Rifammycin
Rifabutin Tr >-6 tui: 300 mg PO mi 24 gi
Rifampin iu tr Tr nh nhi v tr nh: 10-20 mg/kg PO hoc IV mi 24 gi, ti a 600 mg
lao PO mi 24 gi
Rifaximin Tr >= 12 tui: 200 mg PO mi 8 gi
Aminoglucoside (nn hiu chnh liu da trn im nh v y dng cong nng )
Streptomycin 20-30mg/kg/ngy IM, chia liu mi 12 gi, iu tr lao: 20-40mg/kg IM mi

24 gi, ti a 1g/ngy
Gentamycin - Tr<5 tui: 7.5 mg/kg/ngy IV hoc IM chia liu mi 8 gi
- Tr >= 5 tui: 6-7.5 mg/kg/ngy IV/IM chia liu mi 8 gi hoc liu duy
nht trong ngy: 5mg/kg IV/IM mi 24 gi
Tobramycin Tr nh nhi v tr nh: 6-7.5 mg/kg/ngy IV/IM chia liu mi 6-8 gi
Amikacin Tr nh nhi v tr nh: 15-22.5 mg/kg/ngy IV/IM chia liu mi 8 gi
Nhm Macrolide
Erythromycin Tr nh nhi v tr nh: dng bazo, mui estolate v mui strearate: 30-50
mg/kg/ngy PO chia liu mi 6-8 gi, ti a 2g/ngy. Dng mui
Ethylsuccinate: 30-50mg/kg/ngy PO chia liu mi 6-8 gi, ti a
3.2g/ngy. Dang mui lactobionate: 15-50 mg/kg/ngy chia liu mi 6 gi,
ti a 4g/ngy
Azithromycin Tr >=6 thng tui:
- Nhim trng ng h hp: 10mg/kg/ngy trong ngy 1 (ti a
500mg/ngy), tip tc 5mg/kg PO mi 24 gi ngy th 2 n th 5 (ti a
250mg/ngy)
- Vim tai gia: 30mg/kg PO liu duy nht (ti a 1500mg)
- Phc 3 ngy: 10mg/kg PO mi 24 gi trong 3 ngy, ti a 500mg/ngy
- Phc 5 ngy: 10mg/kg PO ngy th 1 (ti a 500mg), 5mg/kg PO mi
24 gi t ngy th 2-5 (ti a 250mg)
Clarithromycin Tr nh nhi v tr nh: 15 mg/kg/ngy PO, chia liu mi 1 gi
Nhm Tetracycline
Tetracycline Tr>8 tui: 25-50 mg/kg/ngy PO, chia liu mi 6-12 gi, ti a 3g/ngy
Minocycline Tr>8 tui: 4mg/kg PO liu u tin, sau 4mg/kg/ngy PO chia liu mi
12 gi
Chloraphenicol Tr nh nhi >30 ngy tui v tr nh: 50-100 mg/kg/ngy PO/IV, chia liu
mi 6 gi, ti a 4g/ngy
Clindamycin - Tr nh nhi v tr nh: dang hydrocloride 8-20 mg/kg/ngy PO, dng
palmitate 8-25 mg/kg/ngy PO, chia liu mi 6-8 gi
- Tr >1 thng tui: 20-40 mg/kg/ngy IV/IM chia liu mi 6-8 gi
Nhm Streptogramin
Quinupristin/Dalf 7.5 mg/kg IV mi 8-12 gi

opristin
Linezolid Tr nh nhi v tr nh: 30 mg/kg/ngy PO/IV, chia liu mi 8 gi
Nitrofurantoin - Tr > 1 thng tui (Furadantin, Macrodantin): 5-7mg/kg/ngy PO, chia
liu mi 6 gi, ti a 400mg/ngy
- Tr > 12 tui ( Macrobid): 100mg PO mi 12 gi
Trimetoprim/ Tr > 2 thng tui:
sulfamethoxazol -Nhim trng nh-va: 6-10mg (tnh theo trimetoprim)/kg/ngy PO/IV chia
liu mi 12 gi cho n 15-20mg/kg/ngy PO/IV, chia liu mi 6-8 gi
Quinolon Khng c s dng cho tr nh hn 16 tui
Metronidazole Tr nh nhi v tr nh: 30-50 mg/kg/ngy PO/IV, chia liu mi 6-8 gi, ti
a 4g/ngy
Cc khng sinh khc: s dng 1 ln/ngy
Isoniazid Tr nh nhi v tr nh: 10-15 mg/kg/ngy, liu duy nht PO, ti a

300mg/ngy
Rifampin iu tr Tr nh nhi v tr nh: 10-20mg/kg/ngy, liu duy nht, PO
lao
Pyrazinamide Tr nh nhi v tr nh: 15-30mg/kg/ngy, liu duy nht PO, ti a 2g/ngy
227
Ethambutol Tr nh nhi v tr nh: 15-25 mg/kg/ngy, liu duy nht, ti a 2.5g/ngy,
thn trng vi tr < 13 tui
Ch : cc liu khuyn co trn khng s dng i vi tr s sinh.

BD. UptoDate. Available at: http://www.uptodate.com. Accessed February 2011; Micromedex
Healthcare Series (http://www.micromedex.com). Greenwood Village, CO: Thomson Micromedex;
2006; Clinical Pharmacology. Tampa, FL: Gold Standard, Inc., 2006. Available at:
http://www.clinicalpharmacology.com. Accessed September 2006; American Society of Health-
System Pharmacists.AHFS Drug Information 2011. Bethesda, MD: American Society of Health-
System Pharmacists; 2011.
Ph lc 3. Liu khng sinh ngi trng thnh suy gim chc nng thn
THANH
THI
CREATININE
TC NHN (CrCl) (mL/min) LIU TIU BIU*#$
Penicillin G >50 2-4 triu n v IV mi 4 gi

10-50 2-4 triu n v IV mi 6 gi
<10 1-2 triu n v IV mi 6 gi
Penicillin V >10 500 mg PO mi 6 gi

<10 500 mg PO mi 8 gi
Nafcillin Khng cn chnh 2 g IV mi 4 gi

liu theo chc
nng thn
Oxacillin <10 iu chnh xung khong thp hn liu dng thng

thng
Dicloxacillin Khng cn chnh 500 mg PO mi 6 gi

liu theo chc
nng thn
Cc aminopenicillin
Ampicillin >50 2 g IV mi 6 gi
10-50 2 g IV mi 6-12 gi
<10 2 g IV mi 12 gi
Amoxicillin >30 500 mg PO mi 8 gi

10-30 500 mg PO mi 12 gi
<10 500 mg PO mi 24 gi
229
Ampicillin- >30 2 g (ampicillin) IV mi 6 gi
sulbactam 15-30 2 g IV mi 12 gi
<15 2 g IV mi 24 gi
Amoxicillin- >30 500 mg (amoxicillin) PO mi 8 gi

clavulanate 10-30 500 mg (amoxicillin) PO mi 12 gi (Vin nn 875 mg
khng nn c dng vi CrCl <30)
<10 500 mg (amoxicillin) PO mi 24 gi
Amoxicillin- >30 2 g PO mi 12 gi
clavulanate phng <30 Khng s dng
thch ko di
Penicillin ph rng
Piperacillin >40 4 g IV mi 8 gi
20-40 3-4 g IV mi 8 gi
<20 3-4 g IV mi 12 gi
Penicillin ph rng + cht c ch -lactamase
Piperacillin- >40 3,375 g (piperacillin) IV mi 6 gi hoc 4,5 g IV mi 8

tazobactam gi
20-40 2,25 g IV mi 6 gi hoc 3,375 g IV mi 6 gi
<20 2,25 g IV mi 8 gi hoc 2,25 g IV mi 6 gi
Ticarcillin- >60 3,1 g IV mi 4 gi

clavulanate 30-60 2 g IV mi 4 gi
10-30 2 g IV mi 8 gi
<10 2 g IV mi 12 gi
Cefazolin >55 1 g IV mi 6-8 gi

35-54 1 g IV mi 8 gi
11-34 1 g IV mi 12 gi
<10 1 g IV mi 24 gi
Cefadroxil >25 500 mg PO mi 12 gi

10-25 500 mg PO mi 24 gi
<10 500 mg PO mi 36 gi
Cephalexin >40 500 mg PO mi 6 gi

10-40 500 mg PO mi 8 gi
<10 500 mg PO mi 12 gi
Cefotetan >30 1-2 g IV mi 12 gi

10-30 1-2 g IV mi 24 gi hoc 1 g IV mi 12 gi
<10 1-2 g IV mi 48 gi hoc 500 mg IV mi 12 gi
Cefoxitin >50 1-2 g IV mi 6 gi

30-50 1-2 g IV mi 8-12 gi
10-30 1-2 g IV mi 12-24 gi
5-10 0,5-1 g IV mi 12-24 gi
<5 0,5-1 g IV mi 24-48 gi
Cefuroxime >20 750 mg IV mi 8 gi

10-20 750 mg IV mi 12 gi
<10 750 mg IV mi 24 gi
Cefuroxime axetil Khng cn chnh 250 mg PO mi 12 gi

liu theo chc
nng thn
Cefprozil >30 500 mg PO mi 12 gi

<30 250 mg PO mi 12 gi
Cefaclor >10 500 mg PO mi 8 gi

<10 250 mg PO mi 8 gi
Loracarbef >50 400 mg PO mi 12 gi

10-50 200 mg PO mi 12 gi hoc 400 mg PO mi 24 gi
<10 200-400 mg PO mi 3-5 ngy
Cefotaxime >20 1-2 g IV mi 8 gi

<20 1 g IV mi 8 gi
Ceftazidime >50 1-2 g IV mi 8 gi

30-50 1-2 g IV mi 12 gi
15-30 1-2 g IV mi 24 gi
6-15 1 g IV mi 24 gi
<6 1 g IV mi 24-48 gi
Ceftriaxone Khng cn chnh 1 g IV mi 24 gi
231
liu theo chc
nng thn
Cefdinir >30 600 mg PO mi 24 gi

<30 300 mg PO mi 24 gi
Cefditoren >50 400 mg PO mi 12 gi

30-50 200 mg PO mi 12 gi
<30 200 mg PO mi 24 gi
Cefpodoxime >30 200 mg PO mi 12 gi

<30 200 mg PO mi 24 gi
Ceftibuten >50 400 mg PO mi 24 gi

20-50 200 mg PO mi 24 gi
<30 100 mg PO mi 24 gi
Cefixime >60 400 mg PO mi 24 gi

20-60 300 mg PO mi 24 gi
<20 200 mg PO mi 24 gi
Cefepime >60 1-2 g IV mi 12 gi

30-60 1-2 g IV mi 24 gi
10-30 1 g IV mi 24 gi
<10 500 mg IV mi 24 gi
Ceftaroline >50 600 mg IV mi 12 gi

30-50 400 mg IV mi 12 gi
Cc carbapenem
Imipenem/cilastatin >70 (Tt c liu u tnh theo imipenem da trn cn nng

70 kg)
500 mg IV mi 6 gi
40-70 500 mg IV mi 8 gi
20-40 250 mg mi 6 gi
6-20 250 mg mi 12 gi
<6 Khng s dng
Meropenem >50 1 g IV mi 8 gi
25-50 1 g IV mi 12 gi
10-25 500 mg IV mi 12 gi
<10 500 mg IV mi 24 gi
Ertapenem >30 1 g IV mi 24 gi
<30 500 mg IV mi 24 gi
Doripenem >50 500 mg IV mi 8 gi

30-50 250 mg IV mi 8 gi
10-30 250 mg IV mi 12 gi
Monobactam
Aztreonam >30 2 g IV mi 8 gi
10-30 1 g IV mi 8 gi
<10 500 mg IV mi 8 gi
Cc glycopeptide
Vancomycin >70 1 g (15 mg/kg) IV mi 12 gi

50-70 1 g (15 mg/kg) IV mi 24 gi
<50 1 g (15 mg/kg) IV vi khong cch gia cc liu da trn
nng thuc trong huyt thanh
Telavancin >50 10 mg/kg IV mi 24 gi

30-50 7,5 mg/kg IV mi 24 gi
<50 10 mg/kg IV mi 48 gi
Daptomycin >30 4-6 mg/kg IV mi 24 gi

<30 4-6 mg/kg IV mi 48 gi
Cc rifamycin
Rifampin Khng cn chnh 600 mg PO mi 24 gi

liu theo chc
nng thn
Rifabutin Khng cn chnh 300 mg PO mi 24 gi

liu theo chc
nng thn
Rifapentine Khng cn chnh 600 mg PO mi 72 gi

liu theo chc
nng thn
233
Rifaximin Khng cn chnh 200 mg PO mi 8 gi
liu theo chc
nng thn
Cc aminoglycoside (Liu nn c iu chnh da trn nng nh v nng y)
Streptomycin >80 15 mg/kg IM mi 24 gi

50-80 7,5 mg/kg IM mi 24 gi
10-50 7,5 mg/kg IM mi 24-72 gi
<10 7,5 mg/kg IM mi 72-96 gi
Gentamicin >60 Liu quy c: 1,7 mg/kg IV mi 8 gi;

liu mt ln/ngy: 4-7 mg/kg IV mi 24 gi
40-60 Liu quy c: 1,7 mg/kg IV mi 12 gi;
<20 Da trn nng thuc trong huyt thanh
Tobramycin >60 Liu quy c: 1,7 mg/kg IV mi 8 gi;

Amikacin >60 Liu quy c: 15 mg/kg/ngy IV chia nhiu liu mi 8-12

gi; liu mt ln/ngy: 15 mg/kg IV mi 24 gi
40-60 Liu quy c: 7,5 mg/kg mi 12 gi;
liu mt ln/ngy: 15 mg/kg IV mi 36 gi
20-40 Liu quy c: 7,5 mg/kg mi 24 gi;
liu mt ln/ngy: 15 mg/kg IV mi 48 gi
Erythromycin Khng cn chnh 1 g IV mi 6 gi

liu theo chc 500 mg PO mi 6 gi
nng thn
Azithromycin Khng cn chnh 500 mg IV mi 24 gi 500 mg PO x 1,

liu theo chc sau 250 mg PO mi 24 gi
nng thn
Clarithromycin >30 500 mg PO mi 12 gi

<30 250 mg PO mi 12 gi hoc 500 mg PO mi 24 gi
Telithromycin >30 800 mg PO mi 24 gi

<30 600 mg PO mi 24 gi
Cc tetracyline v glycylcycline
Tetracycline >80 500 mg PO mi 6 gi

50-80 500 mg PO mi 8-12 gi
10-50 500 mg PO mi 12-24 gi
<10 Khng s dng
Doxycycline Khng cn chnh 100 mg IV/PO mi 12 gi

liu theo chc
nng thn
Minocycline Khng cn chnh 100 mg PO mi 12 gi

liu theo chc
nng thn
Tigecycline Khng cn chnh 100 mg IV liu u tin, sau 50 mg IV mi 12 gi

liu theo chc
nng thn
Chloramphenicol Khng cn chnh 500 mg IV/PO mi 6 gi

liu theo chc
nng thn
Clindamycin Khng cn chnh 600-900 mg IV mi 8 gi

liu theo chc 150-450 mg PO mi 6 gi
nng thn
Streptogramin
Quinupristin/dalfopri Khng cn chnh 7,5 mg/kg IV mi 8 gi

stin liu theo chc
nng thn
Linezolid Khng cn chnh 600 mg IV/PO mi 12 gi

liu theo chc
nng thn
235
Nitrofurantoin >60 Furadantin, Macrodantin: 50-100 mg PO mi 6 gi
<60 Macrobid: 100 mg mi 12 gi chng ch nh
Trimethoprim- >30 2,5 mg/kg IV mi 6 gi

sulfamethoxazole 1 vin DS PO mi 12 gi
15-30 1,25 mg/kg IV mi 6 gi
1 vin SS PO mi 12 gi
<15 Khng c khuyn co
Cc quinolon
Ofloxacin >50 400 mg PO mi 12 gi

20-50 400 mg PO mi 24 gi
<20 200 mg PO mi 24 gi
Ciprofloxacin >50 400 mg IV mi 12 gi

500 mg PO mi 12 gi
30-50 400 mg IV mi 12 gi
250-500 mg PO mi 12 gi
5-30 200-400 mg IV mi 18-24 gi
250-500 mg PO mi 18 gi
<5 250 mg IV mi 24 gi
250 mg PO mi 24 gi
Levofloxacin >50 500-750 mg IV/PO mi 24 gi

20-50 250 mg IV/PO mi 24 gi hoc
750 mg IV/PO mi 48 gi
10-20 250 mg IV/PO mi 48 gi hoc
500 mg IV/PO mi 48 gi
Moxifloxacin Khng cn chnh 400 mg IV/PO mi 24 gi

liu theo chc
nng thn
Gemifloxacin >40 320 mg PO mi 24 gi

<40 160 mg PO mi 24 gi
Metronidazole >10 500 mg IV/PO mi 6 gi

<10 250 mg IV/PO mi 6 gi
Cc tc nhn khng lao
Isoniazid Khng cn chnh 300 mg PO mi 24 gi

liu theo chc
nng thn
Rifampin Khng cn chnh 600 mg PO mi 24 gi

liu theo chc
nng thn
Pyrazinamide >30 25-35 mg/kg PO mi 24 gi

<30 25-35 mg/kg PO x 3 ln/tun
Ethambutol >50 15-25 mg/kg PO mi 24 gi

10-50 15-25 mg/kg PO mi 24-36 gi
<10 15-25 mg/kg PO mi 48 gi
* Liu thc s c th thay i ty thuc vo ch nh, mc nng ca nhim trng v c im

ca bnh nhn.
#
Nhng khuyn co ny khng p dng vi ngi ang c thm phn.
$
Liu loading c th cn mt s khng sinh.
c chp thun bi Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic
Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America:
treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167:603662; Cunha BA. Antibiotic
Essentials. Royal Oak, MI: Physicians Press; 2004; Gilbert DN, Moellering RC Jr, Eliopoulos GM,
et al. The Sanford Guide to Antimicrobial Therapy, 2011. 41st ed. Sperryville, VA: Antimicrobial
Therapy, Inc.; 2011; Rose BD. UptoDate. Available at: http://www.uptodate.com. Accessed
February 2011; Micromedex Healthcare Series (http://www.micromedex.com). Greenwood Village,
CO: Thomson Micromedex; 2006; Clinical Pharmacology. Tampa, FL: Gold Standard, Inc., 2006.
Available at: http://www.clinicalpharmacology.com. Accessed September 2006; American Society
of Health-System Pharmacists. AHFS Drug Information 2011. Bethesda, MD: American Society of
Health-System Pharmacists; 2011.
237
Ph lc 4. Khng sinh trong thai k
Cc khng sinh khc nhau v an ton trong thai k cng nh v cch s dng ng trong thai k
c nghin cu. T , C quan Qun l Dc phm v Thc phm Hoa K chia cc khng
sinh vo nm nhm phn loi s dng cho ph n mang thai:
Nhm A: Cc nghin cu y , c kim sot trn ph n mang thai khng cho thy c s gia
tng nguy c nhng bt thng bo thai.
Nhm B:
(1) Cc nghin cu trn ng vt cho thy khng c bng chng gy hi vi bo thai; tuy
nhin, khng c cc nghin cu y trn ph n mang thai; hoc
(2) Cc nghin cu trn ng vt cho thy tc ng bt li nhng cc nghin cu y trn
ph n mang thai tht bi trong vic chng minh nguy c vi bo thai.
Nhm C:
(1) Cc nghin cu trn ng vt cho thy tc ng bt li v khng c cc nghin cu y
trn ph n mang thai; hoc
(2) Khng c cc nghin cu trn ng vt c tin hnh v khng c cc nghin cu y
trn ph n mang thai.
Nhm D: Cc nghin cu trn ph n mang thai chng minh nguy c vi bo thai nhng li ch
ca tr liu c th cao hn nguy c c th c.
Nhm X: Cc nghin cu trn ng vt hoc trn ph n mang thai chng minh bng chng tch
cc v nhng bt thng hoc nguy c vi bo thai. Do , vic s dng b chng ch nh ph n
mang thai hoc c th bt u mang thai.
TC NHN PHN LOI NGUY C THAI K
Penicillin G B
Penicillin V B
Nafcillin B
Oxacillin B
Dicloxacillin B
Cc aminopenicillin
Ampicillin B
Amoxicillin B
Ampicillin-sulbactam B
Amoxicillin-clavulanate B
Cc penicillin ph rng
Piperacillin B
Cc penicillin ph rng + cht c ch -lactamase
Piperacillin-tazobactam B
Ticarcillin-clavulanate B
Cefazolin B
Cefadroxil B
Cephalexin B
Cefotetan B
Cefoxitin B
Cefuroxime B
Cefuroxime axetil B
Cefprozil B
Cefaclor B
Loracarbef B
Cefotaxime B
239
Ceftazidime B
Ceftriaxone B
Cefdinir B
Cefditoren B
Cefpodoxime B
Ceftibuten B
Cefixime B
Cefepime B
Cc carbapenem
Imipenem/cilastatin C
Meropenem B
Ertapenem B
Doripenem B
Monobactam
Aztreonam B
Cc glycopeptide
Vancomycin C
Telavancin C
Daptomycin B
Colistin C
Cc rifamycin
Rifampin C
Rifaximin C
Rifabutin B
Cc aminoglycoside
Streptomycin D
Gentamicin D
Tobramycin D
Amikacin D
Erythromycin B
Azithromycin B
Clarithromycin C
Telithromycin C
Cc tetracycline v glycylcycline
Tetracycline D
Doxycycline D
Minocycline D
Tigecycline D
Chloramphenicol C
Clindamycin B
Linezolid C
Nitrofurantoin B
Trimethoprim-sulfamethoxazole C
Cc quinolon
Ofloxacin C
Ciprofloxacin C
241
Levofloxacin C
Moxifloxacin C
Gemifloxacin C
Metronidazole B
Cc tc nhn khng lao
Isoniazid C
Rifampin C
Pyrazinamide C
Ethambutol B
Antimicrobial Therapy, 2011. 41st ed. Sperryville, VA: Antimicrobial Therapy, Inc.; 2011; Briggs
GG, Freeman RK, Yaffe SJ. Drugs in Lactation and Pregnancy. 7th ed. Philadelphia, PA: Lippincott
Williams & Wilkins; 2005.
Ph lc 5- Thuc gc v bit dc cc khng sinh thng dng
Tn thng mi Tn gc Tn thng mi Tn gc
Amikin Amikacin Ery-Ped Erythromycin
ethylsuccinate
Amoxil Amoxicillin Ery-Tab Erythromycin
Ancef Cefazolin Erythrocin Erythromycin
lactobionate
Augmentin Amoxicillin Clavulanate Factive Gemifloxacin
Avelox Moxifloxacin Flagyl Metronidazole
Azactam Azetreonam Floxin Ofloxacin
Bactrim Trimethoprim- Fortaz Ceftazidime
sulfamethoxazole
Biaxin, Biaxin XL Clarithromycin Furadantin Nitrofurantoin
Ceclor Cefaclor Garamycin Gentamicin
Cedax Ceftibuten Geocillin Carbenicillin
Cefotan Cefotetan Ilosone Erythromycin estolate
Ceftin Cefuroxime axetil Ilotycin Erythromycin
Cefzil Cefprozil Invanz Ertapenem
Cipro, Cipro XR Ciprofloxacin Keflex Cephalexin
Claforan Cefotaxime Kefurox Cefuroxime
Cleocin Clindamycin Ketek Telithromycin
Coly-Mycin M Colistin Lamprene Clofazimine
Cubicin Daptomycin Levaquin Levofloxacin
Doribax Doripenem Lorabid Loracarbef
Duricef Cefadroxil Macrobid Nitrofurantoin
Dynapen Dicloxacillin Macrodantin Nitrofurantoin
E.E.S Erythromycin ethylsuccinate Maxipime Cefepime
Eryc Erythromycin Mefoxin Cefoxitin
Minocin Minocycline Merrem Meropenem
Myambutol Ethambutol Spectracef Cefditoren pivoxil
Mycobutin Rifabutin Suprax Cefixime
My-E Erythromycin stearate Synercid Quinupristin/
Dalfopristin
243
Nafcil Nafcillin Tazicef Ceftazidime
Nebcin Tobramycin Teflaro Ceftaroline
Omnicef Cefdinir Ticar Ticarcillin
Omnipen Ampicillin Timentin Ticarcillin-clavulanate
Pediamycin Erythromycin ethylsuccinate Tygacil Tigecycline
Pfizerpen Penicillin G Unasyn Ampicillin-sulbactam
Pipracil Piperacillin Unipen Nafcillin
Polycillin Ampicillin Vancocin Vancomycin
Polymox Amoxicillin Vantin Cefpodoxime proxetil
Priftin Rifapentine Veetids Penicillin V
Primaxin Imipenem-cilastatin Vibativ Telavancin
Principen Ampicillin Vibramycin Doxycycline
Prostaphlin Oxacillin Xifaxan Rifaximin
Rifadin Rifampin Zinacef Cefuroxime
Rimactane Rifampin Zithromax Azithromycin
Rocephin Ceftriaxone Zmax Azithromycin ER
Septra Trimethoprim- Zosyn Piperacillin-
sulfamethoxazole tazobactam
Zyvox Linezolid
Amikacin Amikin Clarithromycin Biaxin, Biaxin XL
Amoxicillin Amoxil, Polymox Clindamycin Cleocin
Amoxicillin- Augmentin Clofazimine Lamprene
clavulanate
Ampicillin Omnipen, Polycillin, Colistin Coly-Mycin M
Principen
Ampicillin-sulbactam Unasyn Daptomycin Cubicin
Azithromycin Zithromax Dicloxacillin Dynapen
Azithromycin ER Zmax Doripenem Doribax
Aztreonam Azactam Doxycycline Vibramycin
Carbenicillin Geocillin Ertapenem Invanz
Cefaclor Ceclor Erythromycin Ery-Tab, Eryc
Cefadroxil Duricef Erythromycin Ilosone
estolate
Cefazolin Ancef Erythromycin E.E.S., Ery-Ped,
ethylsuccinate Pediamycin
Cefdinir Omnicef Erythromycin Erythrocin
lactobionate
Cefditoren pivoxil Spectracef Erythromycin My-E
stearate
Cefepime Maxipime Ethambutol Myambutol
Cefixime Suprax Gemifloxacin Factive
Cefotaxime Claforan Gentamycin Garamycin
Cefotetan Cefotan Imipenem-cilastatin Primaxin
Cefoxitin Mefoxin Levofloxacin Levaquin
Cefpodoxime proxetin Vantin Linezolid Zyvox
Cefprozil Cefzil Loracarbef Lorabid
Ceftaroline Teflaro Meropenem Merrem
Ceftazidime Fortaz, Tazicef Metronidazole Flagyl
Ceftibuten Cedax Minocycline Minocin
Ceftriaxone Rocephin Moxifloxacin Avelox
Cefuroxime Kefurox, Zinacef Nafcillin Nafcin, Unipen
Cefuroxime axetil Ceftin Nitrofurantoin Furadantin, Macrobid,
Macrodantin
Cephalexin Keflex Ofloxacin Floxin
Ciprofloxacin Cipro, Cipro XR Oxacillin Prostaphlin
Penicillin G Pfizerpen Rifaximin Xifaxan
Penicillin V Veetids Telavancin Vibativ
Piperacillin Pipracil Telithromycin Ketek
Piperacillin- Zosyn Ticarcillin Ticar
tazobactam
Quinupristin/ Synercid Ticarcillin- Timentin
Dalfopristin clavulanate
Rifabutin Mycobutin Tigecycline Tygacil
Rifampin Rifadin, Rimactane Tobramycin Nebcin
Rifapentine Priftin Trimethoprim- Bactrim, Septra
sulfamethoxazole
Vancomycin Vancocin
Da theo Gilbert DN, Moellering RC Jr, Eliopoulos GM, v cng s. The Sanford Guide to
BD. UptoDate. Available at: http://www.uptodate.com. Accessed February 2011.
245
Ph lc 6. iu tr nhim trng do vi khun nhm khng b sinh hc gy ra
Mt s loi c t vi sinh vt c kh nng c s dng lm v kh trong cc v khng b sinh hc.

Nhng vi sinh vt ny c chia l 3 loi: A,B, v C. Cc vi sinh vt thuc nhm A c cho l c
kh nng gy hi cao nht vi cng ng v chng d pht tn v c kh nng gy t vong cao. Hin
nay c 6 loi vi sinh vt c xp vo nhm A bao gm: Bacillus anthracis (gy bnh than),
Clostridium botulinum (bnh ng c clostridium), Yersinia pestis (gy bnh dch hch),
Francisella tularensis (gy bnh tularemia), vi rt bnh u ma, v vi rt gy st xut huyt nh vi
rt Ebola v vi rt Marburg. Trong 6 loi trn, 4 loi u l vi khun, cc khuyn co iu tr nhim
trng lin quan n khng b sinh hc do 4 vi khun khun trn gy ra s c lit k trong bng
sau:
IU TR NHIM TRNG DO VI KHUN NHM KHNG B SINH HC GY RA
TC NHN IU TR
Bacillus anthracis - Ciprofloxacin hoc Doxycycline
gy bnh than + mt trong cc khng sinh sau: rifampin, vancomycin, penicillin,
ampicillin, chloramphenicol, imipenem,
clindamycin,clarithromycin
Clostridium - Chm sc h tr
botulinum gy ng - Khng c t ha tr III
c botulinum - Khng sinh khng c ch nh thng xuyn
Francisella - Streptomycin hoc gentamicin

tularensis gy bnh - C th la chn thay th bng: Doxycyclin/
tularemia Ciprofloxacin/Chloramphenicol
Yersinia pestis gy - Streptomycin hoc Gentamicin

dch hch h hp - La chn thay th: Doxycycline, Ciprofloxacin, Chloramphenicol
Ph lc 7. Ti liu tham kho y khoa
Cc thng tin trnh by trong cun sch ny c bin son t cc ti liu tham kho di y
cng vi cc ti liu c lit k cui mi chng. c gi c tham kho nhng ngun ny
lm tng quan y cho cc kha cnh lm sng v vi sinh hc ca iu tr nhim trng do vi
khun.
Hip hi M v h thng y t dc s, AHFS Drug Information 2011. Bethesda, MD: American
Society of Health-System Pharmacists; 2011.
Brunton LL, Chabner BA, Knollman BC, eds. Goodman & Gilmans The Pharmacological Basis
of Therapeutics. 12th ed. New York, NY: McGraw-Hill; 2010.
Gilbert DN, Moellering RC Jr, Eliopoulos GM, et al. The Sanford Guide to Antimicrobial
Therapy, 2011. 41st ed. Sperryville, VA: Antimicrobial Therapy, Inc.; 2011.
Mandell GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennetts Principles and Practice of
Infectious Diseases. 7th ed. Philadelphia, PA: Elsevier; 2009.
Mascaretti OA. Bacteria versus Antibacterial Agents: An Integrated Approach. Washington, DC:
ASM Press; 2003.
Rose BD. UptoDate. Available at: http://www.uptodate.com. Accessed February 2011.
Walsh C. Antibiotics: Actions, Origins, Resistance. Washington, DC: ASM Press; 2003.
247
Ph lc 8. Ti liu tham kho vn hc
Cc trch dn u ca nhiu chng c ly t nhng ngun sau y:
Anonymous. The Anglo-Saxon Chronicle. Swanton M, trans-ed. New York, NY: Routledge;
1998.
Anonymous. Gesta Stephani. Potter KR, trans-ed. Oxford, England: Clarendon Press; 1976.
Ceasar J. The Battle for Gaul. Boston, MA: David R. Godine, Publisher, Inc.; 1985.
Froissart J. Chronicles. London, England: Penguin Books; 1978.
Josephus. The Jewish War. Harmondsworth, England: Penguin Books; 1986.
Musashi M. The Book of Five Rings. New York, NY: Bantam Books; 1992.
Payne-Gallwey SR. Crossbow. New York, NY: Marlboro Books, Dorset Press; 1989.
Prestwich M. Armies and Warfare in the Middle Ages. The English Experience. New Haven, CT:
Yale University Press; 1996.
Seward D. The Hundred Years War. The English in France, 13371453. New York, NY:
Atheneum; 1978.
Tuchman BW. A Distant Mirror. New York, NY: Ballantine Books; 1979.
Tzu S. The Art of War. Oxford, England: Oxford University Press; 1971.
von Clausewitz C. On War. London, England: Penguin Books; 1982.
Warner P. Sieges of the Middle Ages. Barnsley, England: Pen & Sword Military Classics; 2004.
Ph lc 9. Tr li cu hi ca mi chng
Chng 1
1. peptidoglycan
2. penicillin-binding proteins or PBPs
3. bacilli
Chng 2
1. anaerobic
2. RNA polymerase
3. 50S, 30S, rRNA, proteins
Chng 3
1. deoxynucleotides
2. circular
3. topoisomerases
Chng 4
1. bactericidal
2. Kirby-Bauer
3. broth dilution
Chng 5
1. peptidoglycan
2. penicillins, cephalosporins, carbapenems, monobactams
3. PBPs or penicillin-binding proteins
4. -lactamases
5. -lactam ring, side chain
6. penicillin-binding proteins or PBPs, peptidoglycan
7. gram-negative
8. staphylococci
9. gram-negative bacteria
10. staphylococci, gram-negative bacteria
11. gram-negative bacteria, Pseudomonas aeruginosa
12. gram-positive bacteria, gram-negative bacteria, anaerobic bacteria
13. generations, -lactams
15. gram-positive
16. gram-negative, anaerobic
17. gram-negative
18. Pseudomonas aeruginosa, Enterobacteriaceae
19. methicillin-resistant
20. ceftriaxone
249
21. penicillins
22. cilastatin
23. gram-positive, gram-negative, anaerobic
24. Pseudomonas aeruginosa, Acinetobacter spp.
25. aztreonam
26. gram-negative, gram-positive, anaerobic
27. -lactam
28. gram-positive
29. enterococci
30. peptidoglycan
31. lipoglycopeptide
32. cyclic lipopeptide
33. gram-positive
34. lipopolysaccharide
35. gram-negative
Chng 6
1. RNA polymerase, mRNA
2. mycobacteria, staphylococci
3. resistance
4. gram-negative
5. gram-positive
6. nephrotoxicity, ototoxicity
7. azithromycin, Haemophilus infl uenzae
8. azithromycin, clarithromycin
9. anaerobic
10. ketolide
11. respiratory
12. ribosomes
13. atypical
14. pregnant women, children
15. glycylcyclines
16. gram-positive, gram-negative
17. ribosomes
18. anaerobic, atypical
19. acetylation, effl ux pumps
20. toxicity, bone marrow, aplastic anemia
21. gram-positive, anaerobic
22. macrolides or erythromycin
23. pseudomembranous colitis
24. two
25. gram-positive
26. methicillin, penicillin, vancomycin
27. methicillin, vancomycin
28. ribosomes
29. intravenously, orally
30. gram-negative, gram-positive
31. blood
32. resistance
Chng 7
1. tetrahydrofolate or THF
2. gram-positive, gram-negative
3. HIV
4. leprosy
5. gram-negative, gram-positive
6. ciprofl oxacin
7. moxifl oxacin
8. DNA gyrase, topoisomerase IV
9. cartilage
10. anaerobic
11. microaerophilic
12. reduce
Chapter 8
1. multiple
2. isoniazid, rifampin, pyrazinamide,
ethambutol
3. hepatotoxicity
Chng 10
1. oxacillin, nafcillin
2.methicillin-resistant Staphylococcus aureus or MRSA
3. -lactams
4. vancomycin
5. penicillin, ampicillin
7. cephalosporins, quinolones, vancomycin, telithromycin
8. clindamycin, macrolides, tetracyclines, trimethoprim-sulfamethoxazole
9. penicillin
10. clindamycin
11. penicillin
251
12. aminoglycosides
13. penicillin G, ampicillin, piperacillin
14. vancomycin
15. bacteriostatic, bactericidal
16. linezolid, daptomycin, quinupristin/dalfopristin, tigecycline
17. ampicillin, gentamicin
18. cephalosporins
19. trimethoprim-sulfamethoxazole
20. ciprofloxacin, doxycycline
21. two
Chng 11
1. community, health care
2. trimethoprim-sulfamethoxazole, quinolone
3. Escherichia coli, Klebsiella spp.
4. carbapenems, -lactam/-lactamase inhibitor combinations
5. carbapenems
6. aminoglycoside
7. gastroenteritis, quinolones, third-generation cephalosporins, azithromycin
8. ceftazidime, cefepime
9. piperacillin
10. two
11. antipseudomonal lactams aminoglycosides, extended-spectrum penicillins quinolones
12. penicillin
13. ceftriaxone, cefi xime
14. Chlamydia trachomatis
15. not
16. macrolides, quinolones
17. multiple
18. antibiotic, acid-blocking
19. tetracycline, doxycycline
20. ciprofl oxacin, erythromycin, azithromycin, trimethoprim-sulfamethoxazole
21. -lactamase
22. aminopenicillin -lactamase inhibitor combinations, second generation cephalosporins,
third-generation cephalosporins, tetracyclines
23. azithromycin, clarithromycin, erythromycin
24. trimethoprim-sulfamethoxazole, quinolones, tetracyclines, telithromycin
25. -lactamase
26. sulbactam
Chng 12
1. anaerobic, spore, positive
2. penicillin, metronidazole
3. metronidazole, vancomycin
4. Bacteroides, Prevotella, Porphyromonas
5. -lactam/-lactamase inhibitor combinations, carbapenems, metronidazole,
chloramphenicol
6. clindamycin, piperacillin, moxifloxacin, tigecycline, cephalosporins
Chapter 13
1. macrolides, tetracyclines, quinolones
2. -lactams, amoxicillin
3. macrolides, tetracyclines, quinolones
4. -lactams
5. azithromycin, levofl oxacin, moxifloxacin
6. macrophages
7. doxycycline, gentamicin, streptomycin, rifampin
8. rifampin, gentamicin, streptomycin
9. rifampin, trimethoprim-sulfamethoxazole
10. streptomycin
11. gentamicin
12. tetracycline, doxycycline, chloramphenicol
13. doxycycline
14. tetracycline, chloramphenicol, ciprofloxacin
Chapter 14
1. penicillin
2. stage
3. benzathine penicillin
4. doxycycline
5. amoxicillin, cefuroxime, erythromycin
6. ceftriaxone, penicillin G
7. doxycycline
8. doxycycline, amoxicillin
9. penicillin, ampicillin, ceftriaxone
Chapter 15
1. four
2. isoniazid, rifampin, pyrazinamide, ethambutol
3. streptomycin, amikacin, cycloserine, ethionamide, capreomycin, p-aminosalicylic acid,
quinolone
4. isoniazid
5. two, three
253
6. clarithromycin, ethambutol
7. azithromycin
8. multiple, prolonged
9. dapsone, rifampin
10. clofazimine
Chapter 16
1. Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila
2. macrolides, -lactams, quinolones
3. -lactam, azithromycin, quinolone
4. early-onset, late-onset
5. ceftriaxone, quinolone, ampicillin/sulbactam, ertapenem
6. cephalosporin, carbapenem, piperacillin/tazobactam, quinolone, aminoglycoside,
linezolid, vancomycin
Chapter 17
1. Escherichia coli
2. nitrofurantoin, trimethoprim-sulfamethoxazole
3. enterococci
4. complicated
5. cefepime, quinolone, extended-spectrum penicillin/-lactamase inhibitor combinations,
carbapenem
Chapter 18
1. Neisseria gonorrhoeae, Chlamydia trachomatis, anaerobic
2. cephalosporin, doxycycline, metronidazole
3. cephalosporin, doxycycline, clindamycin, gentamicin
4. Neisseria gonorrhoeae, anaerobic, Chlamydia trachomatis
Chapter 19
1. Streptococcus pneumoniae, Neisseria meningitidis, Listeria monocytogenes

2. third-generation cephalosporin, vancomycin, ampicillin
3. penicillin G, ampicillin
4. ampicillin, gentamicin
Chapter 20
1. Staphylococcus aureus, Streptococcus pyogenes, streptococci
2. dicloxacillin, clindamycin, first, macrolide
3. nafcillin, oxacillin, cefazolin, clindamycin
4. glycopeptide, linezolid, daptomycin, tigecycline, ceftaroline
Chapter 21
1. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis
2. amoxicillin
3. Streptococcus pneumoniae
4. macrolide, azithromycin, clarithromycin
Chapter 22
1. viridans group streptococci, Staphylococcus aureus, enterococci
2. coagulase-negative staphylococci, Staphylococcus aureus
3. penicillin G, ceftriaxone, gentamicin
4. vancomycin, gentamicin
5. vancomycin, rifampin, gentamicin
6. nafcillin, oxacillin, gentamicin
7. ceftriaxone, ampicillin-sulbactam, ciprofloxacin
Chapter 23
1. coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli
2. nafcillin, oxacillin
3. vancomycin
4. ceftazidime, cefepime
Chapter 24
1. facultative and aerobic gram-negative bacilli, gram-positive cocci, anaerobic bacilli
2. Escherichia coli
3. -lactam/-lactamase inhibitor combinations, carbapenems
4. metronidazole
255

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ANTIBIOTIC BASIC FOR CLINIC 2nd

ANTIBIOTIC BASIC FOR CLINIC THE ABCs OF CHOOSING THE RIGHT

PHN I: CC KIN THC C BN V VI KHUN

Hnh 1-1. Cu trc mng t bo vi khun

Hnh 1-2. Cu trc peptidoglycan. Tng hp peptidoglycan cn lin kt cho cc polyme

CU HI (li gii xem Ph lc 9)

Chng 2: Sn xut protein

Ging nh tt c cc i qun xm lc, vi khun gy bnh cn phi c tip t. Chng cn cc

Hnh 2-1. Tng quan qu trnh sn xut protein trong vi khun.

Qu trnh tng hp cc protein mi i hi mt lng di do cc khi vt liu ti to cng nh

C TB c nhn in hnh v vi khun, cc cu trc i phn t l ribosome u thc hin cng

Hnh 3-1. Tng hp tetrahydrofolate vi khun .

yu t ny. Cho nn con ng tng hp ny l mt mc tiu hp dn cho cc hp cht khng

Hnh 3-2. Qu trnh siu xon trong cu trc xon kp ca DNA.

Hnh 3-3. Ti to cc nhim sc th ca vi khun. Mt h qu chu k t nhin cc nhim sc th

Chng 5: Khng sinh tc dng ln thnh ca t bo

Nu thnh t bo (cell envelop) l o gip ca vi khun, th cc khng sinh nhm beta-

Cc khng sinh -Lactam

Hnh 5-1. Cu trc vng beta-lactam

Bng 5-1: Khng sinh nhm beta-lactam

Nh l trng hp vi tt c cc khng sinh, s khng ca vi khun vi nhm beta-

Khng thuc thng do mt khng sinh b tht bi vi t nht mt trong vic ng u vi

Hnh 5-3. C ch ca s c ch protein ni penicillin (PBP) bi cc khng sinh beta-lactam.

Hnh 5-4. Hot ng ca cc lactam c th b chn bi su c ch: (1) S xm nhp, (2)

V d, cc beta-lactamase tit bi t cu vng tng i c hiu vi mt s loi penicilin,

Mi mt penicillin bao gm mt vng thiazolidine gn vi mt vng beta-latam m bn thn

Kt qu ca s thay i mch nhnh R, nhm penicilin chia thnh mt vi di nhm: cc

Hnh 5-5. Cu trc ca cc penicillin.

Bng 5-2. Nhm penicillin

Bi v gn nh tt c vi khun c thnh t bo u cha thnh phn peptidoglycan, khng c

Mc d nhng hn ch ny, cc penicillin t nhin vn c s dng iu tr nhim trng

Hnh 5-7. Chui R ca nafcillin

Bi v chng khng th lin kt vi PBPs ca vi khun MRSA v MRSE, cc penicillin

Hnh 5-8. Chui R ca ampicillin

PHI HP AMIOPENICILLIN/CC CHT C CH BETA-LACTAMASE:

Hnh 5-9. Chui R peperacillin

hot ng ni tri khng li vi khun gram m, gram dng v k kh ca n khin

LU : Penicillin G v penicillin V: Loi no tim? Loi no ung?

Mi cephalosporin bao gm mt nhn vi 2 mch nhnh (Hnh. 5-10). Nhn l 7-

Hnh 5-10. Cu trc cc cephalosporin

Kt qu l chng c ch trong vic iu tr nhim trng gy ra bi nhiu chng ca

Cc cephalosporin th h I khng th lin kt vi cc PBP ca MRSA v MRSE hoc nhiu

Cc cephalosporin th h I c hot tnh hn ch chng li vi khun gram m hiu kh v ty

Hnh 5-11. Cu trc ca cefazolin

Cc cephalosporin th h II ring bit khc nhau hot ng ca chng chng li vi khun

S thay i ph bin ca cu trc nhiu cephalosporin th h III l dng nhm

Citrobacter freundii, Providencia spp., Morganella morganii, v Serratia spp.,ban u cng

Mt khuyt im ca hu ht cc cephalosporin l thiu hot ng chng li P. aeruginosa.

Gia nhng cephalosporin th h III, ceftriaxone l ng ch bi thi gian bn thi di

Hnh 5-14. Cu trc cefepime. Nhm cu trc in hnh ca cephalosporin th h III R1 l

Tm li, cc cephalosporin khc nhau ni bt cc hot ng ca chng, nhng theo cc th

1 6. So snh vi cc khng sinh th h I, cc cephalosporin th h II tng ph hot ng

Nu xem cc lactam nh l mt gia nh rng ln th cc carbapenem l nhng th h tr

Cu trc ca cc carbapenem lin quan ti cu trc cc penicillin hay cephalosporin (Hnh 5-

Cu trc ca cc carbapenem to ra 3 tnh cht gip cho ph hot ng rng mt cch ni

Vic khng cc carbapenem xy ra khi vi khun nh bi c cc im mnh ca nhng

Chng nhanh chng b phn hy thn bi enzyme gi l dehydropeptidase. Kt qu l n

Imipenem c ph hot ng chng li nhiu tc nhn vi khun gy bnh (Bng 5-16). Hu

23. Carbapenems c hot tnh ni tri tr hiu kh, hiu kh v

Thut ng monobactam c s dng m t mt s thuc khng sinh do nhiu vi sinh vt

Hnh 5-17. Cu trc ca aztreonam. Chui R1 tng t vi ceftazidime.

V d mt chui nhnh trong cu trc ca azetreonam dng nhm aminothiazolyl gip ci

Nh kt qu ca vic thit k cng thc, aztreonam tip cn v kt ni kh tt vi cc PBPs