CHNG 3.

KHNG SINH KHNG KHUN

BI 1. TC NG CA KHNG SINH
V S KHNG CA VI KHUN
MC TIU HC TP
1. Trnh by c nhng c ch tc ng khc nhau ca cc nhm khng sinh, khi
nim v khng sinh ph thuc thi gian v khng sinh ph thuc nng
2. Nu c bn c ch khng khng sinh chnh ca cc vi khun v k cc yu t
thun li cho pht trin khng khng sinh.
3. Nu cc tnh cht phn bit s khng khng sinh do t bin nhim sc th v
do plasmid.
4. Trnh by v ba loi tc dng ph ca khng sinh km theo cc th d c th.
NI DUNG BI HC

1. TC NG KHNG SINH
1.1. NH NGHA
Khng sinh khng khun l cc cht:

C ngun gc sinh hc hay tng hp.

Tc ng mt cch chuyn bit trn mt giai on chnh yu trong s bin dng

ca cc vi khun.

1.2. CC NGUYN TC V TC NG CA KHNG SINH V S PHNG V

CA VI KHUN
Tc ng ca khng sinh

S phng v ca vi khun

c tc ng mt khng sinh cn

Vi khun phng v bng cch

i vo c trong vi khun

Bin i thnh vi khun tr nn

khng thm i vi khng sinh

Khng b ph hy hay bin i bi Bi tit cc men c hiu lc v hot

cc khng sinh
vi khun
Tm c mt im ch ti Bin i im ch ca khng sinh
khng sinh gn vo gy xo trn thnh khng dung nhn khng sinh hay
cu trc vi khun hay lm ri lon
Hy b im ch
bin dng ca vi khun
Thm vo im ch mi
1

1.3. KHNG SINH PH THUC THI GIAN V KHNG SINH PH THUC

NNG
Hot tnh dit khun ca nhng khng sinh ph thuc vo 2 thng s:

Thi gian tip xc

Nng khng sinh

Ty theo loi khng sinh m mt trong hai yu t trn chim u th.

Cc khng sinh ph thuc nng c hot tnh thay i theo nng ca thuc.
nng cao, nh hng thi gian tc ng ca khng sinh b gii hn. Hiu lc dit
khun l thuc nng thng l rt nhanh chng.

Th d: Aminoglycosid, Fluoroquinolon v imipenem trn trc khun Gram m

Cc khng sinh ph thuc thi gian c hot tnh b nh hng bi thi gian tc ng
ca thuc. Hiu lc gia tng km hay khng gia tng theo nng khng sinh d
cht ny c tnh dit khun. Hiu lc dit khun ph thuc thi gian thng xy ra
chm.

Th d: cc Beta - lactam, Glycopeptid, Quinolon v rifampicin i vi cu khun

Gram dng.
Tuy nhin, khi nim v hiu lc dit khun ph thuc thi gian v ph thuc nng
khng c ngha tuyt i: l v hiu lc ny khng ch ph thuc vo phn t
thuc m cn ph thuc vo loi vi khun
Ph thuc thi gian
Beta - lactam (tr imipenem)
Glycopeptid
Fluoroquinolon (trn Staphylococcus)
Rifampicin

Ph thuc nng
Imipenem
Aminoglycosid
Fluoroquinolon (trn trc khun Gram m)

1.4. C CH TC NG CA KHNG SINH

Phn ln cc khng sinh tc ng trn cc khu chnh thuc qu trnh bin dng ca
t bo vi khun v c th tc ng theo 4 c ch chnh nh sau:
c ch s tng hp thnh ca vi khun (c ch s tng hp peptidoglycan)

Beta - lactam c ch transpeptidase

Vancomycin c ch giai on cui ca s tng hp bng to phc vi dipeptid

Fosfomycin c ch pyruvyl tranferase

Cc cht c ch s tng hp protein cn cho vi khun

Macrolid: giai on bt u.

Tetracyclin, chloramphenicol: giai on to chui acid amin

Aminoglycosid: c ch c 2 giai on.

Cc cht c ch s tng hp hay c ch chc nng ca acid nucleic

Nitro - 5 - imidazol, nitrofuran: gy t on phn t DNA

Quinolon: c ch DNA - gyrase

Rifampicin: c ch s sao chp

Sulfamid, trimethoprim: c ch cc enzym tng hp acid nucleic.

Cc cht c ch chc nng mng t bo vi khun

Polymyxin: lm tng tnh thm ca mt s ion, mt i tnh thm thu chn lc ca

mng.

Hnh a.1. C ch tc dng ca cc nhm khng sinh

2. S KHNG CA VI KHUN
2.1. KHNG T NHIN V KHNG THU NHN
khng t nhin: thuc tt c cc chng ca cng mt loi vi khun. Th d:

Streptococcus khng t nhin vi cc Aminoglycosid do thnh vi khun khng

cho khng sinh qua c.

E. coli v P. aeruginosa (trc khun m xanh) khng t nhin vi peniclin G. S

khng t nhin l thuc tnh di truyn ca vi khun.
3

 khng thu nhn:

Do s thu nhn gen mi v thng xy ra. (80 - 90 %). Gen mi ny c th mang

bi mt:
Plasmid: on DNA ngoi nhim th, c th t ti bn
Transposon: cng l mu DNA nhng khng t ti bn c m phi s dng mt
plasmid, hay mt nhim th ca vi khun lm phng tin.
C th truyn s khng t loi vi khun ny sang loi vi khun khc.

Do s t bin nhim sc th v t xy ra (10 - 20 %). S t bin ny mang tnh t

pht.

2.2. C CH KHNG CA VI KHUN

C 4 c ch khng khng sinh chnh:
Bin i v v hot khng sinh vi nhng enzym ca vi khun: y l c ch
thng gp nht, th d:

Enzym betalactamase (ph hy - lactam)

Enzym ca s actyl ha, phosphoryl ha, nuclotidyl ha (bin i cu trc
Aminoglycosid, Macrolid, chloramphenicol)

Bin i im tc ng (im ch) ca khng sinh: S thay i im ch ca

khng sinh thng qua hin tng t bin dn n tnh khng thuc ca vi khun.
Th d s thay i:
- PBP l im tc dng ca cc - lactam.
- Protein l im gn trn n v 30S ribosom ca cc Aminoglycosid.
Lm gim tnh thm ca thnh vi khun: S suy gim sc thu ht hay gia tng lc
y khng sinh ra khi vi khun c th dn n tnh khng thuc, v khi lng
thuc n im tc dng khng cho nng dit khun. Th d: cc vi khun Gram
m c th gii hn kh nng xuyn thm ca - lactam, tetracyclin do s thay i cu
trc cc l (porin) mng ngoi vi khun.
Ngoi ra, s hin din ca mt bm y cng c th gii hn s lng khng sinh vo
vi khun (th d cc Cyclin).
Pht trin mt kiu bin dng khc khng b khng sinh c ch: Cc khng sinh
nhm Sulfamid, trimethoprim.
S khng ca vi khun vi mt nhm khng sinh c th do nhiu c ch (Th d s
khng cc - lactam)

2.3. YU T THUN LI CHO S PHN TN CC CHNG KHNG

S chn lc ra chng khng khng sinh c th do nhiu nguyn nhn nh:
* S dng khng sinh khng ng:

Qu thng xuyn

Mt dng duy nht cho tt c cc bnh nhn

Tr liu n khng sinh (monotherapy)

* S tip cn ca nhng c th b nhim trng.

* S nhn nhanh chng ca cc vi khun (in vivo trong vi gi c s nhn i)
2.4. CC TNH CHT PHN BIT S KHNG DO NHIM SC TH V
KHNG DO PLASMID
KHNG DO NHIM TH

KHNG DO PLASMID

4 nhm khng sinh c s khng ny l: Xy ra i vi tt c cc khng sinh tr 4

Quinolon, furan, polypeptid, rifampicin
nhm bn
khng do t pht

khng do cm ng vi KS

Tn sut thp 10 - 9 - 10 - 10

Tn sut cao 10 - 6 - 10 - 7

Him xy ra: 10 % - 20 % cc khng

Thng xy ra: 80 % - 90 % cc khng

c lp: khng ch xy ra vi mt loi Ph bin: khng vi nhiu khng sinh

khng sinh (xc sut 2 t bin k tip rt hay vi cc nhm khng sinh khc nhau
thp)
Di truyn theo chiu dc v ngang :
Di truyn theo chiu dc: cc vi khun
- Cc vi khun cng h
cng mt h.
- Cc vi khun khc h

3. TC DNG PH CA KHNG SINH

3.1. TC DNG PH V MT VI TRNG HC
Ri lon h tp khun bnh thng ng rut:
C th xy ra khi dng cc khng sinh c ph khng khun rng, nht l khi dng qua
ng ung (Tetracyclin, Chloramphenicol...)
Kt qu: H tp khun bnh thng b thay bng cc vi khun khng nh t cu
khun, khun m xanh, vi khun h khun ung rut hay cc nm v dn n
- Tiu chy ko di, vim i trng gi mc
- Bnh nm Candida rut
- Thiu vitamin
5

 S chn lc ra cc chng khng:

Khng sinh c s dng c th chn lc ra cc vi khun khng vi chnh n v
khng vi nhiu khng sinh khc.
Tai bin do s phng thch mt lng ln ni c t ca vi khun
Th d: Phn ng try tim mch khi dng liu cao chloramphenicol tr thng hn
(phn ng Herxheimer)
3.2. PHN NG D NG
Xy ra do c s qu mn mt s ngi bnh, c th nh nh: m ay, ban n
nng nh st, kh th, tiu ra m hay ra mu, chong phn v c th dn n t vong.
S xut hin cc phn ng ny khng ph thuc liu dng.
Cc khng sinh thng gy d ng nh cc Penicillin, Sulfamid
3.3. TAI BIN DO C TNH
Cc tai bin ny c trng cho tng loi khng sinh:

Tai bin thn: Aminoglycosid, Sulfamid,...

Tai bin thnh gic: Aminoglycosid, Vancomycin,...

Tai bin huyt hc: Chloramphenicol, Sulfamid,...

Tai bin thn kinh: Penicillin liu cao...

Tai bin cho thai nhi: (B tn hi hoc qui thai, d tt) Tetracyclin, Sulfamid,
Chloramphenicol, Imidazol, Furantoin, Quinolon,...

Tai bin cho tr con: Chloramphenicol, Tetracyclin,...

4. PHN LOI CC NHM KHNG SINH KHNG KHUN

Nhm khng sinh c ch s tng hp thnh vi khun

Cc - lactam

Cc Glycopeptid

Nhm khng sinh c ch s tng hp protein

Cc Macrolid

Cc Tetracyclin

Cc Aminoglycosid

Chloramphenicol

Clindamycin

Quinupristin, Daflopristin

Linezolid

 Nhm Quinolon
Nhm Sulfamid v cc phi hp thuc c Sulfamid
Thuc khng lao v iu tr phong
Cc nhm khng sinh khc

BI 2. KHNG SINH TC NG
C CH TNG HP THNH VI KHUN
MC TIU HC TP
1. K cc cht tiu biu v thng c s dng trong iu tr nhim trng ca nhm
khng sinh.
2. Gii thch c ch tc ng ca thuc v nu c ch khng ca vi khun i vi
khng sinh.
3. M t ph khng khun l thuyt ca khng sinh.
4. M t tc dng ph v c tnh ca cc khng sinh trong nhm.
5. Trnh by v dc ng hc ca nhm khng sinh t vn dng hiu v vic
s dng thuc trn lm sng v s tng tc thuc.
6. Nu cc ch nh tr liu v chng ch nh ca cc khng sinh trong nhm
NI DUNG BI HC

1. CC BETA - LACTAM
Ngy nay, vi s xut hin ca cc phn t mi, cc Beta - lactam c chia ra thnh
bn nhm: cc PENAM, PENEM, CEPHEM v MONOBACTAM. Tt c cc Beta lactam u c chung c ch tc ng v khng thuc.
Ngoi ra, cn nhm thuc c ch men betalactamase khng c hot tnh khng khun,
c dng phi hp vi cc Beta - lactam m rng ph khng khun trn cc vi
khun tit betalactamase.
1.1. C CH TC NG
Cc Beta - lactam tc ng trn thnh vi khun bng cch c ch giai on cui ca s
tng hp peptidoglycan. Phn t Beta - lactam gn vo cc protein PBP (Protein
Binding Penicillin) c hot tnh enzym hin din trn mng vi khun v c ch chc
nng ca cc enzym ny trong s tng hp peptidoglycan. Ty theo nhm th trn
nhn Beta - lactam, cc Beta - lactam c i lc khc nhau i vi PBP.
1.2. C CH KHNG THUC
S khng ca vi khun i vi Beta - lactam c th theo 3 c ch:

S tng hp cc men - lactamase bi vi khun. Tc ng thy phn ca cc men

do vi khun tit ra lm m vng - lactam v khng sinh b mt tc dng. C ch
khng ny c ngun gc plasmid hoc nhim sc th.
S gim tnh thm ca thnh vi khun l s khng c ngun gc nhim sc th
ca vi khun Gram m i vi khng sinh - lactam, c bit vi penicillin G.

S thay i im ch ca khng sinh l s thay i cu trc ha hc ca cc

PBP, c ngun gc nhim sc th v dn n s gim i lc ca im ch i vi
khng sinh.

1.3. CC PENAM HAY PENICILLIN

Tc ng khng khun ca penicillin G (ly trch t nm Penicillium notatum) c
pht hin t nm 1928 bi A. Flemming. Nhiu nm sau , khng sinh c sinh
tng hp bng phng php ln men k ngh vi hiu sut cao cng nh bn tng hp
cho cc dn cht mi dng trong tr liu.
Cc penam hay penicillin gm c:
- Penicillin nhm G, V, A v M.
- Carboxypenicillin.
- Uridopenicillin.
1.3.1. Ph khng khun ca cc khng sinh nhm penam
CC NHM
Penicillin G v V
- Penicillin G (Specilline)
- Benzathin penicillin (Extencilline)
- Penicillin V (Oracillin, Ospen)

PH KHNG KHUN
+ Cu khun Gram (+): lin cu khun, ph cu khun, t cu
khun khng tit penicillinase.
+ Cu khun Gram (-): mng no cu khun, lu cu khun.
+ Trc khun Gram (+): bacillus anthrasis, corynebacterium
diphteria, listeria monocyto genus, clostridium.
+ Treponema pallidium.

Penicillin A (Aminopenicillin)
- Ampicillin (Totapen)
- Amoxicillin (Clamoxyl, Agram)
- Bacampicillin (Bacampicilline,
Penglobe)

L ph khng khun ca penicillin G m rng, thm mt s vi

khun Gram (-):
- E.coli, Samonella, Shigella.
- Proteus mirabilis, Brucella.
- Haemophilus influenza khng tit beta - lactamase.

Penicillin M
- Meticillin
- Oxacillin (Bristopen)
- Cloxacillin (Orbenine)

Tng t ph khng khun penicillin G nhng c bit tc

ng trn:
- T cu khun tit penicillinase nhy meti (meti - S)

- Nafcillin Na (Nafcillin)
Carboxy - penicillin

Ph khng khun ca penicillin A thm:

- Carbenicillin (Pyaopen)

- Trc khun m xanh (P.aeruginosa)

- Ticarcillin (Ticarpen)

- Enterobacter

Ureido penicillin

Ph khng khun ca penicillin A thm:

- Mezlocillin (Baypen)

- Trc khun m xanh

- Piperacillin (Piperilline)

- Enterobacter, Klebsiella, Bacteroides

9

1.3.2. ng hc - Tc dng ph - c tnh - S dng tr liu

Penicillin nhm G v V
Penicillin G b hy mi trng acid dch v nn c s dng qua ng tnh mch
(IV) hay tim bp (IM) dng mui K + hay Na+. Cc dng tc dng ko di (nh
benzathin penicillin) ch c dng ng IM.
Penicillin G c phn b rng ri trong c th nhng cho nhng nng khc nhau
dch v m. Kh nng xm nhp vo dch no ty, m xng, mt, h thn kinh trung
ng km. Tuy nhin, khi mng no b vim nhim, penicillin c th qua d dng hn.
Tim IM, nng ti a trong mu t t 15 - 30 pht sau, thi gian bn thi ngn,
khong 1/2 gi. c thi tr ch yu qua thn v 50 - 60 % liu s dng hin din
trong nc tiu dng c hot tnh.
Tc dng ph
Thng gp l cc biu hin d ng (ch yu da), c th gy sc phn v. Liu cao
ngi suy thn c th gy tc dng ph v mt thn kinh (chng mt, co git) v ri
lon v mu.
Chng ch nh i vi ngi c tin s d ng vi penicillin.
Penicillin V bn hn penicillin G trong mi trng acid nn c dng bng ng
ung. S phn b, thi tr tng t nh penicillin G.
Ch nh tr liu
Cc bnh nhim trng ti ch hay ton thn nh: nhim trng phi, nhim trng huyt,
vim ni tm mc, vim mng no, bnh bch hu, bnh than, giang mai, lu, bnh do
vi khun k kh.
Penicillin G v V khng c hiu lc i vi t cu khun tit penicillinase (90 % cc
chng Staphylococcus) v cc trc khun Gram m. Mt s vi khun nhy cm hin
c kh nng khng do tit beta - lactamase (lu cu khun, Clostridium,
Fusobacterium).
Liu lng:
- Penicillin G: 3 - 6 triu n v / ngy, chia 3 - 4 ln. Trng hp nng c th t 30 40 triu n v / ngy (ngi ln)
- Benzathin - Penicillin (Extencilline): 1,2 - 2,4 triu n v /15 ngy.
- Penicillin V (Oracillin, Ospen): 3 - 4 triu n v/ ngy, chia 3 - 4 ln.
Penicillin nhm A (Amino Penicillin)
- Ampicillin (Totapen): c dng bng ng ung (hp thu t 40 n 50 %), tim
IM hay IV. Phn b km m xng, trung bnh phi. Liu cao c th t nng
tr liu dch no ty. Thi gian bn thi l mt gi. c thi tr ch yu dng
hot tnh qua thn (60 %) v mt (10 - 20 %)
10

- Amoxicillin (Clamoxyl, Agram, Hiconcil): Amoxicillin c hp thu tt qua ng

tiu ha (90 %) v khng b nh hng bi thc n d dy nh ampicillin.
- Bacampicillin (Bacampicilline, Penglobe), Metampicillin (Suvipen) l dng tin
dc (prodrugs) c s dng bng ng ung v hp thu qua h tiu ha nhanh (hn
90 % liu PO). o thi ch yu qua thn dng c hot tnh (70 - 80 %).
c tnh ca nhm: Ngoi cc phn ng d ng cn c th gy cc ri lon tiu ha
nh bun nn, tiu chy, nhim nm Candida do lm xo trn h tp khun rut.
Ch nh: c s dng trong cc bnh l nhim trng nhy cm vi ampicillin thuc
ng h hp, tai mi hng, rng ming, thn, tit niu - sinh dc, tiu ha v gan mt.
Cn hiu chnh liu ngi suy thn.
Liu lng
- Ampicillin: 2 - 4 gam/ ngy, chia 3 - 4 ln. Trng hp nng c th 6 - 12 gam/ ngy.
- Amoxicillin: 0,75 - 1,5 gam/ ngy, chia 3 ln.
- Bacampicillin: 0,8 - 1,6 gam/ ngy, chia 2 ln.
Penicillin nhm M
Cc penicillin nhm M c tnh khng men penicillinase do t cu khun tit ra. Do ,
ch yu dng iu tr cc bnh nhim trng do t cu khun tit penicillinase. Tuy
nhin, xut hin rt sm cc t cu khun khng i vi nhm khng sinh ny do
bin i cu trc ca PBP (t cu khun khng meti hay MRSA: meticillin resistant
Staphylococus aureus).
S phn b m ging penicillin G. Thi gian bn thi ngn (1/2 gi). Thi tr qua
thn, 50 % liu dng c tm thy trong nc tiu.
Cc tc dng ph: Phn ng d ng v ri lon tiu ha. Ngoi ra, meticillin cn c
th gy tai bin l vim thn m k (khng cn c s dng mt s ni). Khng
sinh ny cng khng dng ng ung v hp thu km (30 %) v b phn hy bi acid
dch v. Cc khng sinh penicillin M thng c s dng hin nay l oxacillin,
cloxacillin hay dicloxacillin, c th dng ung hay tim
Liu lng:

Meticillin: 6 - 12 gam/ ngy, chia 4 - 6 ln.

Oxacillin (Bristopen), Cloxacillin (Orbenine): 3 - 6 gam/ ngy, chia 4 ln (IM hay

IV). 2 - 4 gam/ ngy, chia 3 - 4 ln nu dng ng ung.

Dicloxacillin (Diclocil): 1 gam/ ngy, chia 4 ln (ung).

11

Carboxy - Penicillin
Cc khng sinh nhm ny bn vng vi men Cephalosporinase do vi khun tit ra. Do
, cn c hiu lc trn cc vi khun tit Cephalosporinase nh trc khun m xanh
(Pseudomonas aeruginosa), Enterobacter, Proteus, Citrobacter.
Cc Carboxy - penicillin c s dng trong nhng trng hp nhim trng nng do
cc chng nhy cm cho bi khng sinh .
Thi gian bn thi t 1 n 2 gi. Phn b km dch no ty, tt phi. Thi tr
dng c hot tnh qua thn (80 %) v mt (15 %).
Cc phn ng d ng, xo trn da tng t penicillin A. Cn ch n lng mui
cao c trong khng sinh (110 - 120 mg Na/g). C th gy nhc Kali huyt v alcalose
bin dng.
Liu lng:
- Carbnicillin (Pyopen): IV 500 mg/kg/ ngy.
- Ticarcillin (Ticarpen): IV 200 mg/kg/ ngy.
Claventin l dng phi hp ca ticarcillin v acid clavulanic m rng ph khng
khun trn cc vi khun tit penicillinase.
Nhm Ureido - penicillin:
y l nhm khng sinh c ph khng khun rng do bn vng vi men
Cephalosporinase v cng bn vng i vi penicillinase (nu vi khun tit ra mc
thp). Nhm ny c dnh s dng trong cc trng hp nhim trng nng ti ch
hay ton thn nh nhim trng huyt, vim mng no, nhim trng bng, sinh dc tit niu... gy bi cc chng nhy cm, nht l cc vi khun Gram m v vi khun k
kh. Ngoi ra, chng cng c dng lm khng sinh d phng trong phu thut h
tiu ha v sn ph khoa.
c s dng bng ng tim chch (IM, IV).
Thi gian bn thi khong mt gi v c o thi dng c hot tnh qua thn (65 70 %) v qua mt.
Liu lng:
- Mezlocillin (Baypen): 6 - 15 g/ ngy.
- Pipracillin (Piperilline): 6 - 15 g/ ngy.
Tazocilline l dng thuc phi hp ca pipracillin v tazobactam m rng ph
khng khun trong tr liu.

12

1.4. CC CEPHEM HAY CEPHALOSPORIN

Cc Cephalosporin u tin c c lp t nm Cephalosporium acremonium vo nm
1948. Sau , t nhn ca Cephalosporin C, nhiu Cephalosporin vi hot tnh khng
khun cao hn c bn tng hp.
Cc Cephalosporin c chia lm 4 nhm: Cephalosporin th h I, II, III v IV
1.4.1. Ph khng khun ca cc Cephalosporin
KHNG SINH TIU BIU

PH KHNG KHUN

CEPHALOSPORIN I

+ Cu khun Gram (+): lin cu khun, ph

cu khun, t cu khun meti - S.

- Cefalexin (Keforal)
- Cefalotin (Keflin)
- Cefazolin (Kefzol)
- Cefaloridin (Ceforine)

+ Cu khun Gram (-): Neisseria.

+ Trc khun Gram (-): H.influenza, E.coli,
Proteus mirabilis, Klebsiella pneumoniae.

- Cefadroxil (Oracefal)
CEPHALOSPORIN II
- Cefaclor (Alfatil)
- Cefamandol (Kefandol)
- Cefuroxim (Curoxime)
- Cefoxitin (Mefoxin)

Tng t ph khng khun ca th h I nhng

hot tnh trn trc khun Gram m cao hn.
Ngoi ra, cefoxitin v cefotetan cn tc ng
trn vi khun k kh Gram (-): Bacteroides
fragilis.

- Cefotetan (Apacef)
CEPHALOSPORIN III
- Cefoperazon (Cefobis)
- Cefotaxim (Claforan)
- Ceftriazon (Rocephin)
- Ceftazidim (Fortum)

Ph khng khun ca th h II m rng thm

trn:
- Cc vi khun h khun ng rut
- Trc khun m xanh (P.aeruginosa)
(Ceftazidim)

- Cfixim (Oroken)
- Cefpodoxim (Orelox)
- Latamoxef (Moxalactam)
CEPHALOSPORIN IV
- Cefepim (Axepim)
- Cefpirom (Cefrom)

Ph khng chun rng tng t ph khng

khun ca th h III nhng bn hn vi lactamase

13

1.4.2. Cephalosporin th h I
Cc Cephalosporin I c tnh khng penicillinase ca t cu vng (S. aureus) nhng li
khng bn i vi Cephalosporinase ca nhiu vi khun. Phn b tt vo nhiu m c
th, ngoi tr dch no ty. Thi gian bn thi khong 1 gi. c o thi ch yu
qua thn dng c hot tnh.
Thng c s dng trong cc nhim trng tai - mi - hng, h hp, ng tiu, da
do cc vi khun nhy cm vi thuc gy ra.
Liu lng: Mt s Cephalosporin I c dng qua ng tnh mch hoc tim bp,
mt s bng ng ung.
Liu trung bnh ngi ln:

Cefadrin, Cefalexin, Cefadroxin: 2g/ ngy, chia 2 ln, ung.

Cefatrizin: 1g / ngy, chia hai ln, ung.

Cefaloridin: 1,5 3 g / ngy, chia 3 ln, tim bp.

Cefalotin, Cefapirin: 2 - 6 g / ngy, chia 4 - 6 ln tim bp hay tnh mch

Tc dng ph, c tnh

Cc phn ng d ng tng t vi cc penicillin (penicillin c d ng cho vi
Cephalosporin trong 10 - 15 % trng hp.
C th gy au ni tim chch. Cefalotin (Keflin) i khi gy vim tnh mch hay vim
tnh mch huyt khi. Cefaloridin (Ceporine) vi liu 50 mg/kg / ngy c th gy ra
hay lm trm trng thm chng suy thn, nht l khi s dng phi hp vi thuc li
tiu hay cc Aminoglycosid.
C th gy ra cc xo trn v mu nh gim bch cu, gim tiu cu.
1.4.3. Cephalosporin th h II
Cc Cephalosporin th h II tc ng trn t cu khun (meti - S) km hn th h I.
Tuy nhin cc khng sinh ny bn vng hn vi men Cephalosporinase do vi khun
tit v c hot tnh cao hn trn cc trc khun Gram m (H. infuenza, E. coli, P.
mirabilis, Klebsiella).
Cc Cephalosporin II xm nhp tt vo cc m c th, ngoi tr dch no ty. o thi
qua thn.
Ch nh
Nhim trng gy bi cc mm khng vi Cephalosporin I v ampicillin (nhim
trng tai - mi - hng, kh qun - phi, nhim trng mu, ng tiu...).
Phng nga nhim trng trong phu thut (tim mch, chnh hnh...).
Cefoxitin, cefotetan tr nhim trng do Bacteroides fragilis.
14

Vi dng dng bng ng ung: axetil - cfuroxim (Zinnat, Cepazine) c dng cho
nhim trng tai mi hng v kh qun phi, cho hiu qu tt.
Tc dng ph: Phn ng d ng (thng da) nh Cephalosporin I.
Cc khng sinh nhm ny t c s dng hn khi c s xut hin ca nhm
Cephalosporin th h III.
Liu lng: Cc khng sinh ny c dng qua ng tim bp hay tnh mch, ring
cefuroxim cn c dng bng ng ung.

Cefaclor: 0,75 g/ ngy, chia 3 ln, ung.

Cefamandol: 3 - 6g/ ngy, chia lm 3 ln

Cefuroxim: 1 - 2g/ ngy, chia lm 2 - 3 ln

Cefoxitin: 3 - 6g/ ngy, chia lm 3 ln

Cefotetan: 2 - 6g/ ngy, chia lm 2 - 3 ln

1.4.4. Cephalosporin th h III

Cc Cephalosporin th h III bn vng vi nhiu Cephalosporinase hn so vi cc
Cephalosporin th h II v hiu lc c ch cao i vi s tng trng ca vi khun
(C.M.I rt thp). Ph khng khun m rng i vi cc khun h ng rut, vi trc
khun m xanh P. aeruginosa (Ceftazidim, Cefsulodin, Cefoperazon) v vi khun k
kh (Latamoxef).
Khng c hiu lc i vi t cu khun khng meti, Enterococcus.
Cc Cephalosporin III xm nhp vo dch no ty rt tt, do cn c s dng
trong bnh vim mng no c m gy bi vi khun nhy cm vi thuc. c o thi
ch yu qua thn. Ring ceftriazon c o thi mt phn qua mt (40 %) v
cefoperazon c o thi ch yu qua mt (80 %).
Thi gian bn thi (T1/2) thay i ty phn t thuc, c th xp loi nh sau:

T1/2 t 1 n 2 gi: cefotaxim, ceftazidim...

T1/2 t 2 n 3 gi: cefoperazon, latamoxef, cefixim...

T1/2 hn 8 gi: ceftriazon (ch dng 1 ln/ ngy)

Thng ch nh trong nhng trng hp nhim trng nng gy bi cc chng

khng vi cc Beta - lactam khc (c bit cc trng hp nhim trng bnh vin).
C th dng n tr hay tr liu phi hp. Cn dng lm khng sinh d phng trong
phu thut.
Cc Cephalosporin III dng ng ung: cefixim (Oroken), cepodoxim (Orelox)
thng c ch nh trong cc bnh nhim trng ng tai - mi - hng, kh qun phi v ng tiu.

15

Cc Cephalosporin III c th gy cc phn ng d ng (nh cc Beta - lactam khc).

Ngoi ra, nhng xo trn v s ng mu c th xy ra i vi phn t c nhm metil
- thio - ttrazol (nh latamoxef, cefoperazon).
Liu lng trung bnh ngi ln
ng tim bp hay tnh mch:

Cefoperazon (Cefobis): 4 gam/ ngy, chia 2 ln.

Cefotaxim, Ceftazidim (Claforan, Fortum): 3 gam/ ngy, chia 3 ln.

Ceftriazon (Rocephine): 1 - 2 gam/ ngy, 1 ln.

Latamoxef (Moxalactam): 2 gam/ ngy, chia 2 ln.

ng ung:

Cefixim (Oroken): 400 mg/ ngy, chia 2 ln.

Cefpodoxim (Orelox): 200 - 400 mg/ ngy, chia 2 ln.

Cn hiu chnh liu khi dng cefoperazon cho ngi suy gan
1.4.5. Cephalosporin th h IV
Cefepim (Axepim), Cefpirom (Cefrom): c hot tnh khng khun tng t cc
Cephalosporin th h III nhng c bit bn hn i vi cc men - lactamase ph
rng c ngun gc plasmid (nh TEMP - 1, TEMP - 2, SHV - 1, ...). Thuc qua h
thn kinh trung ng tt, c dng iu tr cc trng hp b khng vi
Cephalosporin III (ceftazidim, cefotaxim)
c s dng bng ng tim chch (IV,IM)
Liu lng:

- Nhim trng khng nng: 1g x 2 ln/ ngy (IM hay IV)

- Nhim trng nng: 2g x 2 3 ln/ ngy (IV)

1.4.6. Cephalosporin ph hp
Cefsulodin (Pyocefal): Tc dng ch yu trn trc khun m xanh (Pseudomonas
aeruginosae), khng hp thu qua ng ung, bi tit phn ln qua thn.
IM/IV chm 3 - 6 gam/ ngy, chia 3 - 4 ln.
1.5. CC PENEM (CARBAPENEM)
* Imipenem (Tienam): phi dng dng kt hp vi cilastatin l mt cht c ch
tng tranh, c hi phc men dehydropeptidase thn. Men ny phn hy imipenem
thnh cht v hot. Imipenem bn vng vi nhiu men beta - lactamase do vi khun
tit ra.

16

Ph khng khun: rt rng

- Cc cu khun Gram (+) tr t cu khng - meti.
- Cc cu khun Gram ( - ): Neisseria.
- Cc trc khun Gram ( - ): k c trc khun m xanh v Acinetobacter
- Cc vi khun k kh Gram (+).
- Cc vi khun k kh Gram ( - ), k c Bacteroides fragilis.
Dc ng: Hp thu tt trong phn ln cc m, cng qua dch no ty. Thi gian bn
thi khong 1 gi, hn 90 % c thi tr vo nc tiu. Cn hiu chnh liu ngi
suy thn.
Ch nh:
Trong cc trng hp nhim trng nng, do cc chng khng vi cc khng sinh
khc, nht l trng hp nhim khun nng bnh vin hay b bi nhim.
Cng c dng ngay ban u, trong khi ch i kt qu vi sinh ca mt bnh nhim
trng nguy n tnh mng.
Imipenem l cht cm ng mnh men Cephalosporinase. Trong tr liu khun m xanh
c th phi hp imipenem vi cht c ch btalactamase hay vi mt khng sinh khc
(Aminoglycosid hay Fluoroquinolon) hn ch s khng thuc ca vi khun.
Tc dng ph: cc phn ng d ng, cc phn ng tiu ha nh bun nn, tiu chy.
i khi c phn ng thn kinh nh co git.
Liu dng: 1,5 - 3 g/ ngy, chia 3 - 4 ln, tim truyn chm tnh mch trong 20 - 30
pht.
* Meropenem (Merrem): L khng sinh bn tng hp dng tim tnh mch. Cht ny
khng cn c s kt hp vi cilastatin nh imipenem. Meropenem c ph khng khun
rt gn vi imipenem v hiu lc mnh hn i vi h khun ng rut, H.Influenza,
P. aeruginosa v lu cu khun. Thuc phn b tt cc m, dch c th, k c dch
no ty. c ch nh trong cc trng hp nhim trng nng nh imipenem, c bit
nhim trng bng c bin chng, vim mng no, st ngi gim bch cu trung
tnh, nhim Pseudomonas khng vi imipenem.
Tc dng ph: tng t imipenem nhng t c tnh thn kinh hn.
Liu dng: 500 - 1000 mg mi 8 gi (tim IV hay tim truyn IV)
* Ertapenem (Invanz): cng khng cn kt hp vi cht c ch dehydropeptidase..
Ph khng khun rng, dit khun nhanh i vi hu ht cc tc nhn gy bnh ph
bin cng ng. Tuy nhin, ertapenem khng c hiu lc i vi t cu khng
meticillin, Pseudomonas aeruginosa v Acinetobacter gy nhim trng bnh vin.
Ertapenem c tc ng ko di, c s dng mt ln/ ngy (IV/IM).Vic s dng
17

ertapenem trong iu tr nhim trng c th gp phn bo v hiu lc cho cc khng

sinh d tr nh vancomycin, imipenem hay Fluoroquinolon .
Tc dng ph: d ng, au u, ri lon tiu ha nh bun nn, tiu chy, c th gy
phn ng ni tim hay vim tnh mch
Liu dng: tim truyn IV 1000 mg/mt ln/ ngy.
1.6. MONOBACTAM
Nhm ny cng c mt i din duy nht ang c s dng trong lm sng l
Aztreonam (Azactam).
Ph khng khun
y l khng sinh c ph khng khun chn lc. Aztreonam hon ton khng c hiu
lc trn vi khun Gram dng v vi khun k kh. Tc ng ch yu trn cc trc
khun Gram m hiu kh nh E.coli, H. influenza, Samonella, Shigella, Proteus,
Klebsiella, Pseudo. aeruginosa v cu khun Gram m hiu kh nh lu cu khun,
mng no cu khun.
Tc ng trn khun m xanh ca aztreonam in vitro yu hn ceftazidim (Cefalosporin
III) nhng mnh hn piperacillin.
Thi gian bn thi: 1,7 gi. Thi tr qua ng tiu (60 - 70 %) dng c hot tnh.
Ch nh: trong cc trng hp nhim trng nghim trng do vi khun Gram m, dng
phi hp (nh vi Aminoglycosid) hay n tr.
Tc dng ph: phn ng d ng hay tiu ha.
Liu dng: IM, IV vi liu cho ngi ln t 3 - 8 g/ ngy, chia lm 3 - 4 ln.
1.7. CC CHT C CH BETA - LACTAMASE
Hin c 3 cht c ch beta-lactamase ang c s dng trong lm sng:
- Acid clavulanic
- Sulbactam
- Tazobactam
y l cc cht khng c hoc c tnh khng khun rt yu. Tuy nhin khi c phi
hp vi mt Beta - lactam, cc cht ny c th hi phc phn hot tnh khng khun b
mt do s thy phn khng sinh bi men betalactamase (chnh xc l penicillinase) tit
ra t vi khun.
C ch tc ng: Do cu trc ha hc, cc cht ny c i lc rt mnh i vi men
penicillinase do vi khun tit ra. Do , s gn cht vo cc men ny v to iu kin
cho khng sinh nhm penicillin gn vo cc protein PBP v pht huy hiu lc dit
khun. Ngc li, cc cht c ch betalactamase c i lc rt km i vi cc PBP.

18

Cc beta - lactamase v hiu lc ca cht c ch men: Ngi ta chia cc

btalactamase lm hai nhm chnh: penicillinase v Cephalosporinase. Cc men ny c
th c ngun gc plasmid hay nhim sc th.
- Penicillinase: c tit bi mt s loi vi khun nh t cu khun nhy meti,
Klebsiella, H.influenza, Neisseria, Bacteroides fragilis, E.coli...
S tit penicillinase mc thp s phn hy cc penicillin nhm G, A, v nhm
Carboxypenicillin. c tit mc cao, penicillinase cn c th phn hy c nhm
Uridopenicillin v cc Cephalosporin I, II (tr Cefoxitin).
- Cephalosporinase: c tit bi nhiu trc khun Gram m thng gy cc nhim
trng nng bnh vin nh trc khun m xanh, Enterobacter, Serratia, Citrobacter,
Proteus...
S tit Cephalosporinase mc thp c th gy phn hy cc penicillin nhm G, A v
M (s nhy cm ca cc penicillin thay i i vi enzym ny), cc Cephalosporin th
h I v II v s tit mc cao cn phn hy cc Cephalosporin th h III.
Hin nay, mt s nc, ngi ta cn pht hin mt s vi khun tit ra men beta lactamase ph rng (Extended spectrum beta - lactamase) c kh nng phn hy phn
ln cc khng sinh nhm Penicillin v Cephalosporin.
Cc cht c ch men beta - lactamase (acid clavulanic, sulbactam, tazobactam) tc
ng ch yu trn cc penicillinase v khng c hiu lc c ch hay c ch rt yu
trn cc Cephalosporinase. Ch c tazobactam l c kh nng c ch trung bnh cc
Cephalosporinase. Acid clavulanic cn l cht gy cm ng men Cephalosporinase.
Cc dng phi hp c s dng trong tr liu:
- Acid clavulanic + Amoxicillin (Augmentin, Ciblor).
- Acid clavulanic + Ticarcillin (Claventin).
- Sulbactam + Ampicillin (Unasyn).
- Tazobactam + Pipracillin (Tazocilline).
Sulbactam cn dng khng kt hp (Betamase) v c dng phi hp vi mt Beta
- lactam ty theo s la chn ca ngi cho toa.
Liu lng cho ngi ln:

Augmentin: 1,5 - 2 g/ ngy, chia lm 3 - 4 ln (ung, tim IV).

Claventin: 9 - 18 g/ ngy, chia ln (tim IV chm).

Tazocilline: 12 g/ ngy, chia lm 3 ln (tim IV chm).

Sulbactam: 3 - 4 g/ ngy, chia lm 3 - 4 ln (ung hay IV).

19

Cc phi hp thuc trn thng c ch nh trong cc trng hp sau:

- Nhim trng tai - mi - hng, kh qun - phi cp v mn tnh, nht l trng hp
bnh ph qun mn tnh.
- Nhim trng ng tiu.
- Nhim trng da v m mm.
- Nhim trng ph khoa.

2. NHM GLYCOPEPTID
Vancomycin (Vancocine)
L khng sinh quan trng vi cu trc glycopeptid v c hiu qu trn vi khun a
khng thuc nh MRSA (t cu khun khng meticillin) v Enterococcus trng cu
khun.
Ph tc dng
Vancomycin tc dng ch yu trn cc vi khun Gram dng: Staphylococcus, Strepto
- coccus, Pneumococcus khng penicilin, Enterococcus, c bit trn c MRSA v
MRSE (Staphylococcus aureus v Staphylococcus epidermidis khng meticillin)
Vi khun k kh: Clostridium difficile.
C ch tc dng
c ch s tng hp phospholipid v s polymer ha peptidoglycan thnh vi khun.
S khng
C s khng t nhin vi khun Gram ( - ) v khng thu nhn (plasmid) vi
khun Gram (+) lm gim tnh thm thnh vi khun hay gim gn kt vo im tc
dng.
Dc ng hc
Thng dng tim truyn IV chm tr nhim trng ton thn hay d phng nhim
trng.
Vancomycin khng hp thu qua ng ung nn ng ny thng ch c s dng
trong iu tr vim rut kt mng gi do C. difficile gy bi khng sinh tr liu (trong
trng hp metronidazol khng c hiu lc). Hin tng vim gip thuc c th qua
mng no.
Vancomycin rt t b chuyn ha v 90 % thuc c lc qua qun cu thn trong 24
gi. Cn hiu chnh liu v theo di nng trong mu ngi cao tui hay suy thn
v y l khng sinh c gii hn tr liu hp (T 1/2 bnh thng ca vancomycin t 6 - 10
gi, ngi suy thn giai on cui l 200 h)

20

Tc dng ph - c tnh

Tiu ha: bun nn, tiu chy.

D ng (him) - Hi chng ngi (Red Man Syndrome): xy ra khi tim

truyn nhanh.

c vi thn v thnh gic (tng khi dng kt hp vi Aminoglycosid).

c vi thn kinh: au u, chng mt.

Kch ng ni mc tnh mch (IV)

S dng tr liu

Nhim trng nng do Staphylococcus v Streptococcus: nht l nhim trng mu,

ni mc tim, phc m, khp... tr nhim trng no.

Liu dng

Ngi c chc nng thn bnh thng: 1g hay 10 15 mg/ kg, tim truyn IV chm
(t nht trong 60 pht), mi 12 gi

D phng nhim trng ni tm mc trong phu thut: 1g, IV chm (1 gi trc

phu thut rng ming, ng h hp trn) hay 1g, IV chm, phi hp vi 1,5 mg/
kg gentamicin (1 gi trc phu thut ng tiu ha, tit niu)

Dng ung: Vim rut kt mng gi do Clostridium, vim rut do Staphylococcus

vi liu 125 500 mg, mi 6 gi trong 7 10 ngy

Teicoplanin (Targocid)
L khng sinh c hot tnh khng khun tng t vancomycin nhng c khc bit v
tnh cht dc ng:thi gian bn thi di (40 - 100 h) cho php tim mt ln / ngy v
ngoi tim truyn IV, c th dng ng IV nhanh hay ng IM (tim bp).
Liu dng
6 mg/kg ( ~ 400 mg) IV vo ngy 1, sau 6 mg/kg hay 3 mg/kg (~ 200 mg) IV/IM
vo cc ngy k tip.
Nhim trng nng: 6 mg/kg IV mi 12 gi. Sau 3 liu, dng tip 6 mg/kg mi 24 gi.
C th tng n 12 mg/kg/ngy

21

BI 3. KHNG SINH TC NG
C CH TNG HP PROTEIN VI KHUN
MC TIU HC TP
1. K cc cht tiu biu v thng c s dng trong iu tr nhim trng ca
mi nhm khng sinh :macrolid, aminoglycosid, cyclin, chloramphenicol,
streptogramin v linezolid,
2. Gii thch c ch tc ng ca thuc v nu c ch khng ca vi khun i
vi khng sinh.
3. M t ph khng khun l thuyt ca khng sinh.
4. M t tc dng ph v c tnh ca cc khng sinh trong nhm.
5. Trnh by v dc ng hc ca nhm khng sinh t vn dng hiu v
vic s dng thuc trn lm sng v s tng tc thuc.
6. Nu cc ch nh tr liu v chng ch nh ca cc khng sinh trong nhm.

1. NHM MACROLID
Macrolid l nhng khng sinh c sn xut t cc nm Streptomyces (Erythromycin
t Streptomyces erythreus, 1952) v c cu trc gm mt nhn (vng lacton c t 14 16 nguyn t) gn vi cc phn t ng bng nhng lin kt glycosid.
y l nhng khng sinh c tc ng km khun nng trong huyt tng. Tuy
nhin, m nng thng cao hn v c hiu lc dit khun.
Cc cht tiu biu
Nhm c 14 nguyn t vng lacton:

Erythromycin (Erythrocine, Propiocine)

Troleandomycin (T.A.O)

Roxithromycin (Rulid)

Clarithromycin (Zaclar)

Nhm c 15 nguyn t vng lacton:

Azithromycin (Zithromax)

Nhm c 16 nguyn t vng lacton:

Josamycin (Josacine)

Spiramycin (Rovamycine)

22

1.1. HOT TNH KHNG KHUN

Tc ng ch yu trn cu khun Gram dng: Streptococcus pneumonia (15 - 20 %
khng vi Macrolid), Staphylococcus (Macrolid 16 nguyn t t b khng)
Trc khun Gram dng: Clostridium, Corynebacterium, Listeria
Mm ni bo: Chlamydia, Mycoplasma, Legionella
Neisseria: mng no cu khun, lu cu khun (ch tc ng mc trung bnh)
Khng c hiu lc i vi phn ln cc vi khun Gram m
1.2. C CH TC NG V C CH KHNG
Cc Macrolid c ch s tng hp protein ca vi khun. V tr tc dng ca chng l
tiu n v 50S ca ribosom (tng t chloramphenicol). Ti y chng ngn khng
cho phc hp acid amin - t - RNA thc hin vic gii m di truyn.
S khng t nhin: i vi a s vi khun Gram m
S khng thu nhn: c ngun gc plasmid hay transposon. Cc c ch c
xut:

S bin i (metyl ha) im ch trn ribosom

Lm gim tnh thm ca thuc qua mng vi khun

1.3. DC NG HC
Erythromycin base b ph hy bi acid dch v nn phi s dng bng ng ung
dng capsule hay cc mui stearat, propionat, etyl succinatCc Macrolid mi
(Roxithromycin, clarithromycin) c hp thu tt hn v khng b nh hng bi thc
n d dy. Trong trng hp cn thit, c th s dng erythromycin bng ng tnh
mch (IV) dng gluceptat hay lactobionat.
Cc Macrolid c phn b tt nhiu m: gan, phi, t tng, tuyn tin lit, xng
v qua c nhau thai. Phn tn km dch no ty (LCR).
Thi gian bn hy thay i t 2 gi (erythromycin) n 12 gi (roxithromycin), ring
azithromycin c thi gian bn hy khong 48 gi. Cc thuc c thi tr ch yu qua
mt.
1.4. TC DNG PH - C TNH
- Xo trn tiu ha: bun nn, au bng, st, tiu chy
- i khi c th gp vim gan mt vi erythromycin estolat v troleandomycin
(TAO)
- Erythromycin tim IV: c th gy kch ng, vim tc tnh mch v c th gy c
tnh thnh gic, xon nh (him) nu s dng dng liu cao.
* Chng ch nh ngi b suy gan nng.
23

1.5. TNG TC THUC

Khi dng mt s Macrolid nh erythromycin, troleandomycin, roxithromycin,
josamycin, c th xy ra
+ S tng nng mt s thuc khc trong huyt tng, c th dn n c tnh nh
cc cht t nm ca g (ergotamin), theophyllin, carbamazepin, bromocriptin,
ciclosporin, warfarin, terfenadin, astemizol, digoxin, cisaprid.
+ Dng chung vi cc estrogen, thuc nga thai, troleandomycin cn lm tng kh
nng gy vim gan mt (do nhiu tng tc bt tin v hiu lc km hn
erythromycin, hin nay troleandomycin gn nh khng cn c s dng na)
+ Vi spiramycin : ch c ghi nhn v tng tc thuc vi levodopa v carbidopa (lm
gim tc dng ca 2 thuc ny).
1.6. S DNG TR LIU
- Nhim trng tai mi hng (ORL)
- Nhim trng h hp
- Nhim trng da
- Nhim trng sinh dc (tr lu cu khun)
Do khng khuch tn vo LCR, ch dng phng nga nhim trng mng no
Cc Macrolid c th dng nh thuc thay th trong trng hp d ng vi penicillin
Trong tr liu vim lot d dy c nhim Helicobacter pylori, clarithromycin l khng
sinh c hiu qu cao dit tn gc H. pylori, thng c phi hp vi thuc cha
lot trong iu tr. Th d : Ranitidin/Lanzoprazol + clarithromycin (500mg ) +
amoxicillin (1g) x 2 ln /ngy, t 7-10 ngy.
Clarithromycin c hiu lc rt tt trn Mycoplasma avium ngi b AIDS .
Azithromycin v roxithromycin cng cho tc ng ny nhng km hn.
Liu lng: Liu trung bnh ngi ln (ung)

Erythromycin: 1 - 2g/ ngy, chia 2 - 3 ln, ung trc ba n

Roxithromycin: 0,3g/ ngy, chia 2 ln

Spiramycin: 6 - 9 triu n v/ ngy, chia 2 - 3 ln

Clarithromycin: 0,5 - 1g/ ngy, chia 2 ln

Azithromycin: 0,5 - 1g/ ngy: dng mt ln / ngy ngoi ba n . Trong vim

ng tiu hay vim c t cung do Chlamydia, ch dng liu duy nht 1gam.

Vi cc ch nh khc (nhim trng h hp, da, m mm..) dng 500 mg trong ngy
u, 250 mg/ ngy trong 4 ngy k tip .

24

2. NHM AMINOGLYCOSID (AMINOSID)

Khng sinh u tin ca nhm Aminoglycosid c s dng trong lm sng l
streptomycin, c ly trch t chng Streptomyces griseus (1944). y l nhm khng
sinh c tc ng dit khun.
Ty theo ngun gc, c th chia cc Aminoglycosid ra lm hai loi:
Aminoglycosid thin nhin

Streptomycin (Streptomycine)

Gentamicin (Gentalline)

Kanamycin (Kamycine)

Tobramycin (Nebcine)

Sisomycin (Sisolline)

Neomycin (Neomycine)

Paromomycin (Humatin, Humagel)

Aminoglycosid bn tng hp

Amikacin (Amiklin)

Dibekacin (Debekacyl)

Netilmicin (Netromycine)

Framycetin (Soframycine)

Cht c cu trc tng cn vi nhm Aminoglycosid

Spectinomycin (Trobicine) (t chng Streptomyces spectabilis)

2.1. HOT TNH KHNG KHUN

Cc Aminoglycosid th hin hiu lc dit khun rt nhanh trn:

Trc khun Gram m hiu kh: cc vi khun h khun ng rut, Haemophilus,

Pseudomonas

Trc khun Gram dng: Listeria, Corynebacterium, Mycobacterium

Cu khun Gram dng: Staphylococcus nhy meti

c bit:

Spectinomycin: c tc ng r trn lu cu khun (N. gonorrheae)

Amikacin: c hiu lc trn cc mm a khng nh trong trng hp nhim trng

bnh vin.

Hot tnh ca cc Aminoglycosid tng dn theo th t sau:

25

Streptomycin Kanamycin Gentamicin, Sisomycin Dibekacin, Tobramycin,

Netilmycin Amikacin
Lin cu khun (Streptococcus), ph cu khun (Pneumococcus) v cc vi khun ym
kh khng t nhin vi cc Aminoglycosid.
2.2. C CH TC NG V C CH KHNG
Cc Aminoglycosid gn vo tiu n v 30S ca ribosom vi khun, lm ngn cn s
tng hp protein v cng lm sai lch s phin m ca m - RNA.
Cc c ch ca s khng thuc gm:
+ S gim tnh thm ca mng vi khun (t xy ra v c ngun gc nhim sc th)
+ S gim gn kt ni im tc ng (ch yu vi streptomycin)
+ S v hot bng cc enzym ca s phosphoryl, adenyl hay acetyl ha (thng xy ra
nht v c ngun gc plasmid)
C th c s khng cho hoc khng.
2.3. DC NG HC
Cc Aminoglycosid khng c hp thu qua ng ung. ng s dng l tim bp
hay tim tnh mch chm (45 pht n 1 gi).
Phn tn km vo cc m v dch c th nh m xng, tuyn tin lit, dch ng
h hp, LCRnhng tng i tt qua mng phi v hot dch. Tp trung vi nng
cao thn v tai trong. Phn ng vim lm tng s phn tn qua mng bng v
mng tim.
Thi gian bn hy l 1,5 - 3gi. Cc Aminoglycosid c thi tr ch yu qua thn
dng c hot tnh.
2.4. C TNH CHNG CH NH
* c tnh
c tnh trn thn: s dng liu cao hay liu ko di Aminoglycosid (tr
spectinomycin) nh hng n chc nng ca t bo tiu qun thn v s lc ca cu
thn. Tuy nhin, c s hi phc nu ngng hay gim liu dng. Streptomycin t c
hn so vi cc Aminoglycosid khc. Mt s Aminoglycosid c c tnh trn thn qu
cao, ch c dng c tc ng ti ch nh neomycin,
Cc yu t lm tng c tnh trn thn:

Phi hp vi thuc li tiu

Phi hp vi cc thuc khc c c tnh trn thn: amphotericin B, cefaloridin,

cyclosporin, cc cht loi curar,

S mt nc

26

Tui bnh nhn

c tnh trn tai

S tch t ca Aminoglycosid rt quan trng tai trong v gy tn thng dy thn
kinh s s 8 vi cc triu chng chng mt, bun nn, ri lon thng bng v gim
thnh lc. Cc thng tn ny khng hi phc khi ngng thuc.
c ch thn kinh c
Tc ng c ch thn kinh c t xy ra, tuy nhin c th dn n lit c (curare - like)
nhng ngi b bnh nhc c. Tc dng ph c ch thn kinh c ca cc
Aminoglycosid gim dn theo th t neomycin, kanamycin, amikacin, gentamicin v
tobramycin.
* Chng ch nh

Trn ngi mang thai

Ngi b suy thn nng

Spectinomycin: khng c c tnh trn tai v thn, cc tc dng ph c th xy ra nh

chng mt, bun nn, nhc u, nga, st, au ni tim. Chng ch nh: ph n c
thai v tr em di 15 tui.
2.5. S DNG TR LIU
Do c tnh cao, Aminoglycosid c ch nh gii hn trong cc trng hp sau:
+ Nhim trng huyt, ni tm mc v nhim trng ti ch trm trng.
+ Nhim trng nng do Listeria.
Khi s dng trong 2 trng hp trn hiu lc dit khun ca Aminoglycosid
(gentamicin, tobramycin, amikacin) rt nhanh chng v chng thng c phi
hp vi mt - lactam hay Fluoroquinolon.
+ Nhim trng lu cu khun: spectinomycin
+ Nhim trng lao (trong trng hp khng vi cc thuc khc, nh nhim
Mycobacterium avium ngi b AIDS): streptomycin, kanamycin.
+ Nhim trng ti ch nh da, nim mc mt, tiu ha: neomycin, framycetin,
paromomycin.
Liu lng

Gentamicin, sisomycin, tobramycin: 3 mg/kg/ ngy

Netilmycin: 4 - 7 mg/kg/ ngy

Amikacin: 15 mg/kg/ ngy

Streptomycin: 0,5 - 1,5g/ ngy

Spectinomycin: 2 - 4g/ ngy

27

 ngi b suy gim chc nng thn phi gim liu khng sinh v nu c nn nh
lng nng khng sinh trong huyt thanh iu chnh liu cho ng.
Ngy nay, trong mt s trng hp nhim trng Gram m nng nhng cha nguy
him n tnh mng v cho bnh nhn c chc nng thn cn n nh (Cl Cr > 60ml/ph)
c th dng Aminoglycosid liu duy nht / ngy. Phng php ny c cho l khng
lm gim hiu lc iu tr m lm gim tch ly, c tnh vi thn v tai. Tuy nhin
Aminoglycosid OD (OD = once a day) khng p dng trong mt s trng hp sau:

iu tr ko di > 7 ngy ;

Nhim trng huyt, sc nhim trng.

Nhim trng Staphylococcus, Enterococcus, Pseudomonas, Serratia .

Bnh nhn b gim bch cu trung tnh .

Ph n c thai; tr em ().

Bnh nhn b c trng ; b phng >20 %.

Bnh nhn phi chu thm phn do suy thn (bt k vi phng php no)

3. NHM TETRACYCLIN
3.1. I CNG
Nhm Tetracyclin l nhng khng sinh c ph khng khun rng c s dng bng
ng ung t nm 1948
y l nhm khng sinh c tc ng km khun. V mt dc l, nhm ny c chia
lm hai th h: th h I gm cc cht c thi gian tc ng ngn hoc trung bnh v th
h II gm cc cht c tng hp gn y c thi gian tc ng di.
Th h I
- Oxytetracylin (Terramycine; Solu - Retard..)
- Clotetracylin (Aureomycine; Tetramig..)
- Tetracyclin (Tabiosan; Hexacycline...)
- Demeclocyclin (Lysocline; Rondomycine)
Th h II
- Doxycyclin (Vibramycine)
- Minocyclin (Mynocine)
Cc Tetracyclin c th c ngun gc t nhin (clotetracyclin t Streptomyces
aureofaciens; oxytetracyclin t Streptomyces rimosus) hay bn tng hp (tetracyclin,
methacyclin, doxycyclin, minocyclin)

28

3.2. HOT TNH KHNG KHUN

Ph khng khun ca nhm Tetracyclin rt rng, bao gm nhiu vi khun Gram m,
Gram dng v cc mm ni bo nh Chlamydia, Mycoplasma,
Rickettsia...Tetracyclin cng c hiu lc i vi Treponema, Borrelia...Tuy nhin, do
mc khng ca nhiu loi vi khun nh Streptococcus, Staphylococcus,
Pneumococcus, Pseudomonas, E.coli... nn cc Tetracyclin khng cn c s dng
trong iu tr nhim trng do cc vi khun va k trn.
Minocyclin c xem l cht c hiu lc mnh nht ca nhm, ri n doxycyclin.
Tetracyclin v oxytetracyclin l cc cht c hiu lc yu nht.
3.3. C CH TC NG V C CH KHNG
Cc Tetracyclin tc ng bng cch gn vo tiu n v 30S ca ribosom vi khun,
ngn cn s tng hp protein.
C ch ca s khng c th do vic ngn chn khng sinh i qua mng vi khun
hoc y khng sinh ra ngoi mng bng s chuyn vn tch cc.
C s khng cho gia cc Tetracyclin
3.4. DC NG HC
Khi s dng bng ng ung, phn ln cc Tetracyclin khng c hp thu hon
ton, t l hp thu l 50 - 75 % cho cc cyclin th h I (tr clotetracyclin ch 30 %) v
95 % - 100 % i vi cc cht thuc th h II. S hp thu b gim bi s hin din ca
thc n (nht l thc n ch bin t sa) v cc cht khng acid (hydroxyt Mg, Al...)
Cc Tetracyclin gn vo protein huyt tng v c phn phi tt cc m, c bit
c kh nng thm nhp vo trong t bo. Vt qua hng ro mu - no km. Qua c
nhau thai v hin din trong sa. Tch tr gan, t tng, xng v rng.
Thi gian bn hy ty mi cht thay i t 5 - 19 gi v di nht vi cc Tetracyclin
th h II (ch cn s dng 1 - 2 ln/ ngy)
S o thi ch yu qua ng tiu, ngoi tr doxycyclin c thi tr qua mt (c
dng cho ngi thiu nng thn m khng phi iu chnh liu). Cc Tetracyclin c
chu k gan - rut.
3.5. TC DNG PH - C TNH
Trn da: Da d nhy cm vi nh sng (nht l doxycyclin, demeclocyclin)
Xo trn tiu ha: nn ma, tiu chy, vim rut, bnh candidose...
Xo trn gan, thn: c th gy tn thng gan v suy thn khi s dng liu cao
tr em di 8 tui, gy bt thng xng v lm rng c mu vng vnh vin.
i khi c th gp phn ng d ng nh nga, ni mn, hen... ; phn ng vim tnh
mch khi tim tnh mch; xo trn v mu nh gim tiu cu, thiu mu tiu huyt.
29

Cc tc dng ph v c tnh gim nhiu i vi cc cht cyclin th h II.

3.6. CHNG CH NH

D ng vi cc Tetracyclin

Ph n c thai v cho con b

Tr em di 8 tui

Suy gan hay thn nng (c th dng doxycyclin ngi suy thn)

3.7. THN TRNG - TNG TC THUC

Tip xc trc tip vi nh sng mt tri v tia UV.
Cc ion kim loi, nht l Ca, Al, mg, cc thuc khng acid lm gim hp thu cc
Tetracyclin. Doxycyclin v minocyclin tan d trong lipid nn t b nh hng hn.
Cc Tetracyclin lm tng hiu lc chng ng ca cc thuc khng vitamin K.
Cc cht gy cm ng h microsom gan (barbiturat, diphenylhydantoin) lm gim thi
gian bn hy ca doxycyclin.
3.8. S DNG TR LIU
Cc Tetracyclin thng c dng bng ng ung. ng tim bp (oxytetracyclin,
doxycyclin) t dng v gy au (ch phm phi phi hp vi thuc t). ng tim
tnh mch (minocyclin, doxycyclin) cng t s dng v c th gy vim tnh mch.
Tuy c hiu lc mnh, minocyclin t c dng hn doxycyclin v c th gy sm da
v tng p lc s no.
Ch nh:

Nhim trng ng h hp do Chlamydia, Mycoplasma

Nhim trng sinh dc do Chlamydia hay nhng chng nhy cm

Nhim trng do cc vt cn ca sc vt (Pasterellose, Tularemie...)

Bnh Brucellose, phi hp vi rifampicin

Bnh Lyme, Rickettsiose

Mn nht

Mt ht (dng thuc m 1 % v vin ung)

Liu lng (ung)

Oxytetracyclin, tetracyclin: 1,5 - 2g/ ngy, chia 2 - 4 ln, ung lc i.

Demeclocyclin, methacyclin: 0,6g/ ngy, chia 2 - 4 ln.

Doxycyclin, minocyclin: 0,2g/ ngy, chia 1 - 2 ln.

30

4. NHM PHENICOL
Nhm Phenicol gm hai khng sinh l chloramphnicol (Tifomycin) v thiamphnicol
(Thiophenicol, Fluimucil). Chloramphenicol c trch ly t chng Streptomyces
venezuela vo nm 1947 v c tng hp ha hc t nm 1948. Do c ph khng
khun rng v kh nng phn tn tt vo cc m c th, chloramphenicol rt c a
chung trong tr liu. Tuy nhin t nm 1950 s pht hin c tnh ng k trn c
quan to mu gii hn vic s dng cht ny trn lm sng. Thiamphenicol l dn
cht tng hp ca chloramphenicol.
4.1. HOT TNH KHNG KHUN
Ph khng khun rng, bao gm:

Vi khun Gram m: Haemophilus influenza, Samonella, Neisseria (no cu khun

v lu cu khun), Brucella, Shigella, E.coli

Vi khun Gram dng: Streptococcus, Staphylococcus, Pneumococcus

Vi khun k kh: Clostridium, Bacteroides

Vi khun ni bo: Chlamydia, Mycoplasma, Rickettsia

Cc Phenicol l nhng khng sinh km khun, tuy nhin cng c hiu lc dit khun
trn vi loi. Th d: H. influenza
4.2. C CH TC NG V C CH KHNG
Chloramphenicol c ch s tng hp protein ca vi khun. Cht ny gn vo tiu n
v 50S ca ribosom, ngn chn s thnh lp cu ni peptid gia cc acid amin.
im gn ca cc Phenicol trn 50S - ribosom rt gn vi im tc ng ca nhm
Macrolid v Lincosamid nn c th tng tranh vi cc cht thuc 2 nhm ny.
S khng thuc ca vi khun c ngun gc plasmid v ch yu do s tit enzym
acetyl transferase lm chloramphenicol mt hot tnh.
Ngoi ra, vi loi nh E.coli, trc khun m xanh (P.aeruginosa) s khng l do
s gim tnh thm ca vi khun i vi thuc.
4.3. DC NG HC
Khi dng qua ng ung, cc Phenicol c hp thu rt tt (chloramphenicol: 75 - 90
% v thiamphenicol gn nh hon ton).
Cc Phenicol xm nhp tt vo nhiu m ca c th: LCR, no, xng khp, phi,
mng bng v c bn trong t bo.
Chloramphenicol c chuyn ha gan (glucuro hp) thnh dn cht mt hot tnh.
S o thi ch yu qua ng tiu v ch mt phn rt nh (2 - 3 %) vo mt.

31

Thiamphenicol khng b chuyn ha gan v c o thi dng khng i, c hot

tnh vo nc tiu (70 %) v vo mt (5 %). Do o, cht ny cn c dng tr
nhim trng gan mt v ng tiu.
Thi gian bn hy ca chloramphenicol l 2 - 3 gi v thiamphenicol l 2,5 - 3,5 gi.
4.4. TC DNG PH - C TNH
c tnh trn s thnh lp mu
Dng nh: gin on s to mu tm thi (suy ty ba dng), xy ra sm, ph thuc
liu v c th hi phc khi ngng tr liu. Thng do s dng liu cao hay b thiu
nng thn.

Dng nng: suy ty xy ra chm, khng th tin on, khng lin quan n liu
lng v c th gy t vong. Vi chloramphenicol, t l mc phi l 1/25.000 trng
hp v rt him i vi thiamphenicol. Phn sut t vong l 80 %.

Hi chng xm (Grey Syndrome)

Xy ra khi dng chloramphenicol tr em s sinh (di 6 thng) hay tr sinh non do
chc nng gan cha hon chnh. Triu chng: i ma, au bng, tiu chy, try mch,
nim mc ti xm, thng dn n t vong.
Try tim mch khi dng liu cao tr thng hn.
Phn ng d ng, ri lon tiu ha.
4.5. CHNG CH NH

Ph n c thai v cho con b.

Tr s sinh di 6 thng tui.

Ngi thiu nng thn (thiamphenicol) v thiu nng gan (chloramphenicol) nng.

Ngi c triu chng suy ty.

4.6. S DNG TR LIU

Do c tnh cao trn h mu, ngy nay cc Phenicol ch c dng gii hn trong
trng hp nhim trng nng, m cc loi thuc khc t c tnh hn b chng ch nh
hay tr nn v hiu do s khng ca vi khun.
Cc ch nh tr liu chnh l

Thng hn v ph thng hn.

Vim mng no, p-xe no do vi khun, c bit do vi khun k kh.

Nhim trng ph qun phi.

Nhim trng gan mt.

Nhim trng do vi khun k kh.

Vic s dng cc Phenicol cn c s theo di cng thc mu trc khi tr liu v 1 - 2

ln mi tun trong khi iu tr. Khng nn s dng qu 3 tun. Cn theo di chc nng
32

gan, thn v iu chnh liu lng i vi ngi suy gan (chloramphenicol) hay thn
(thiamphenicol).
Liu lng

Chloramphenicol: 2 - 3g/ ngy (tr em: 50 mg/kg/ ngy), chia 3 - 4 ln, ung

Thiamphenicol: 1,5 - 3g/ ngy (tr em: 30 - 100 mg/kg/ ngy), chia 2 - 3 ln, ung,
tim bp hay tnh mch

Chloramphenicol: 0,4 % nh mt: 1 git x 3 - 8 ln/ ngy, trong 7 ngy

4.7. TNG TC THUC

Gy c ch s chuyn ha ca mt s thuc khc (sulfamid h ng huyt, thuc
khng vitamin K..), lm tng nng nhng thuc ny trong mu v c th dn n tai
bin trong tr liu.

5. NHM STREPTOGRAMIN HAY SYNERGISTIN

y l cc khng sinh c ngun gc t Streptomycetes v s bin i ha hc.

Pristinamycin (Pyostacine) dng ung

Quinupristin 150 mg + Dalfopristin 350 mg (Synercid) dng tim truyn chm (phi
hp 2 thnh phn vi t l 30:70)

Ph tc dng:

C tc dng ch yu trn vi khun Gram(+), c chng khng vi khng sinh

khc (Staphylococcus, Enterococcus, Gonococcus,..) vi khun k kh, vi khun ni
bo.

khng t nhin vi trc khun Gram ( - ) hiu kh (h khun ng rut,

Pseudomonas).

C ch tc ng v s khng:

c ch tng hp protein do gn kt trn n v 50S ca ribosom vi khun.

Tnh khng c ngun gc plasmid v theo c ch vi khun tit enzym v hot

khng sinh hay dng bm y thuc ra ngoi.

Dc ng hc

Hp thu t 15 - 20 % qua ng ung, phn b tt vo cc m (da, xng, phi,

gan, thn), ngoi tr dch no ty.

Thuc c chuyn ha qua gan, bi tit vo mt (90 %), ch mt phn nh vo

nc tiu.

Tc dng ph

Ri lon tiu ha (ph thuc liu): bun nn, i ma, tiu chy..
33

Rt him: d ng da, au c khp

Kch ng tnh mch (dng chch)

Do c ch Cyt 450 gan (CYP3A4) phi hp quinupristin + dalfopristin c th gy

tng tc vi cc thuc chuyn ha qua isoenzym ny v dn n c tnh.

S dng tr liu

Nhim t cu vng khng meticillin (MRSA) da, m mm, xng khp, phi - ph
qun

Nhim trng sinh dc (lu, vim tuyn tin lit.), trng cu khun khng
vancomycin (VRE)

Thay penicillin trong nhim trng phi - ph qun, ORL, H. influenza, vi khun k
kh.

Hip lc (nht l trong iu tr t cu) vi cc Aminoglycosid, rifampicin,

Fluoroquinolon, vancomycin, acid fusidic..

6. LINEZOLID
Linezolid (Zyvox) l khng sinh tng hp hon ton, c cu trc oxazolidinon mi a
vo tr liu t nm 2000, vi c tnh c hiu lc trn cc chng Gram dng khng
thuc.
Ph khng khun:
Linezolid l khng sinh km khun c ph tc dng ch yu trn VK Gram dng:

Staphylococcus, Streptococcus, Enterococcus, Corynebacterium, Listeria cytomo nogenes.

Cng c tc dng trn Mycobacterium tuberculosis v Clostridium perfringens

C ch tc ng v s khng:
Linezolid c ch s tng hp protein bng cch gn vo n v 50S ca vi khun v
b khng do vi khun t bin lm gim kh nng gn thuc vo im ch.
Cha thy c s khng cho vi cc khng sinh khc.
Dc ng hc
Linezolid dc hp thu hon ton qua ng ung, cng c th dng dng tim tnh
mch. Thuc c phn phi rng ri trong c th v c chuyn ha gan. Mt
trong hai cht chuyn ha c hot tnh khng khun. Linezolid c bi tit mt phn
qua thn. T1/2 khong 4 5 gi.
Tc dng ph - c tnh: dung np tt, mt s tc dng ph t xy ra gm:

34

Ri lon tiu ha: bun nn, tiu chy..

au u, mn nga..

Gim tiu cu c hi phc sau hn 2 tun tr liu.

C kh nng c ch khng chn lc MAO, dn n gy tng tc thuc (vi pseudo

- ephedrin, propanolamin..) hay lm tng nng cc catecholamin trong c th .

S dng tr liu
c ch nh trong iu tr nhim trng phi, da v cu trc da, nhim VRE (trng
cu khun khng vancomycin) v MRSA.
c dng nh thuc lun phin vi vancomycin, c bit trong iu tr cho bnh
nhn ni tr. Vic dng khng ng KS ny dn n s khng linezolid ca VRE
ti mt s ni.
Liu lng

VRE: 600 mg PO/IV mi 12 gi trong 14 28 ngy

Nhim trng bnh vin (nhim trng phi, da/ cu trc da c bin chng): 600 mg
PO/ IV mi 12 gi trong 10 14 ngy

Nhim trng da hay cu trc da khng bin chng: 400 mg, PO, mi 12 gi trong
10 14 ngy

35

BI 4. NHM QUINOLON
MC TIU BI HC
1. Trnh by v phn loi ca khng sinh nhm Quinolon v hat tnh khng khun
ca cc cht tiu biu cho mi phn nhm.
2. Gii thch c ch tc ng ca thuc v nu c ch khng ca vi khun i vi
khng sinh.
3. Trnh by v tnh cht dc ng, tc dng ph v c tnh ca cc khng sinh
trong nhm.
4. Nu cc ch nh tr liu, chng ch nh v cc tng tc thuc chnh ca khng
sinh nhm Quinolon
NI DUNG BI HC
Nhm Quinolon gm nhng khng sinh c tng hp hon ton bng phng php
ha hc. T lu, cc Quinolon c chia thnh hai phn nhm:

Quinolon th h I cn gi Quinolon ng tiu.

Quinolon th h II hay Fluoroquinolon.

Cc Quinolon l nhng khng sinh dit khun.

1. CC CHT TIU BIU

Quinolon ng tiu

Acid nalidixic (Negram)

Acid pipemidic (Pipram)

Acid oxolinic (Urotrate)

Flumequin (Apurone)

Rosoxacin (Eracin)

Cc Fluoroquinolon

Pefloxacin (Peflacin)

Sparfloxacin (Sparflo, Zagram)

Ofloxacin (Oflocet)

Levofloxacin (Levaquin)

Norfloxacin (Noroxine)

Gatifloxacin (Tequin)

Ciprofloxacin (Ciflox,Cipro)

Moxifloxacin (Avelox)

Trovafloxacin (Trovan)

36

Hin nay, nhng nh iu tr cn phn cc Quinolon thnh 4 th h, da trn ph tc

dng v ch nh tr liu ca chng nh sau:

Th h 1: cc Quinolon ng tiu nh acid nalidixic

Th h 2: Ofloxacin, norfloxacin, ciprofloxacin

Th h 3: Sparfloxacin, levofloxacin, gatifloxacin, moxifloxacin.

Th h 4: Trovafloxacin

2. HOT TNH KHNG KHUN

Quinolon ng tiu: c ph khng khun hp:

Tc ng ch yu trn cc vi khun Gram m: E. coli, Shigella, Salmonella,

Klebsiella, Proteus, Enterobacter...

Khng c hiu lc trn cc vi khun Gram dng v trc khun m xanh (P.
aeruginosa)

Rosoxacin cn c tc ng trn lu cu khun (N. gonorrhea)

Cc Fluoroquinolon:

Hiu lc trn ph khng khun ca cc Quinolon th h I cng thm hot tnh trn:

T cu khun nhy meti (mnh) v khng meti (yu).

Lu cu khun, mng no cu khun.

Haemophilus influenza

Trc khun m xanh

Mm ni bo: Chlamydia, Mycoplasma.

* Levofloxacin l ng phn quang hc ca ofloxacin. Hiu lc in vitro ca

levofloxacin mnh gp 2 ln ofloxacin i vi nhiu vi khun hiu kh Gram m v
Gram dng, bao gm trc khun lao. Nng trong huyt tng cho bi 2 dng
ung v tim IV c xem l tng ng.
* Sparfloxacin, levofloxacin, gatifloxacin, moxifloxacin: ph rng, c hiu lc tt
hn cc Fluoroquinolon khc trn vi khun Streptococcus pneumonia, tuy nhin tc
ng yu hn ciprofloxacin trn P.aeruginosa v mt s vi khun Gram m khc. Do
c thi gian bn thi di, cc cht ny c th ch dng mt liu/ ngy.
* Trovafloxacin (PO) v dng tin dc alatrofloxacin (IV): C hiu lc trn nhiu
vi khun Gram dng v Gram m, c bit trn cc vi khun khng thuc. Ngoi ra
cn tc dng trn vi khun k kh.
Tng t levofloxacin, cc cht ny cho nng trong huyt tng nh nhau khi s
dng dng ung v tim IV. C c tnh trn gan.
37

Cc Quinolon c hiu ng hu khng sinh (4 - 8 gi) i vi cc vi khun Gram (-)

v Gram (+). Do , c th ko di khong cch gia cc ln dng thuc n 12 gi.

3. C CH TC NG V C CH KHNG
Cc Quinolon c ch s ti bn hay sao chp ca phn t DNA bng cch c ch hai
enzym topoisomerase II (hay DNA - gyrase) v topoisomerase IV vi khun. Cc
enzym ny c vai tr gip cho s xon v tho xon DNA l hin tng cn thit cho
s sao chp hay ti bn vi khun. vi khun Gram m, DNA - gyrase nhy cm vi
tc ng ca Quinolon hn topoisomerase IV v ngc li, vi khun Gram dng
topoisomerase IV l im tc ng chnh ca cc Quinolon.
S khng ca vi khun vi Quinolon c ngun gc nhim sc th do s t bin
gen to men DNA - gyrase hay topoisomerase IV. C s khng cho gia cc
Fluoroquinolon.

4. DC NG HC
Cc Quinolon c hp thu tt qua ng tiu ha.
Cc Quinolon th h I (tiu biu l acid nalidixic) phn b km cc m, c o
thi ch yu qua thn vi mt phn dng c hot tnh.
Cc Quinolon th h II (fluoro Quinolon) c phn b rt tt m, nht l m phi,
xng, tuyn tin lit, LCR v tai mi hng. Norfloxacin phn b m km hn cc
Fluoroquinolon khc. Cc cht nh sparfloxacin, gatifloxacin, moxifloxacin,
trovafloxacin c thi gian bn thi di nn ch cn dng mt ln/ ngy.
Cc Fluoroquinolon u c o thi ch yu qua ng tiu c hai dng c hot
tnh v mt hot tnh do b chuyn ha. Ring pefloxacin v trovafloxacin c o
thi phn ln qua mt.

5. TC DNG PH - C TNH
Nhy cm vi nh sng (da), c bit khi s dng sparfloxacin nu tip xc trc tip
nh nng c th b tn thng tng t phng 2.
Ri lon tiu ha: bun nn, tiu chy
Ri lon thn kinh: au u, chng mt, mt ng
au khp v c khi tr liu ko di
Tn thng gn Achill
Ri lon v mu: thiu mu tiu huyt ngi thiu G6PD.
c tnh trn gan (Trovafloxacin), c th gy suy gan.
Ko di khong QT (Sparfloxacin)

38

6. S DNG TR LIU
Quinolon th h I v norfloxacin: c ch nh trong nhim trng ng tiu, tuyn
tin lit. Ring rosoxacin c dng trong nhim lu cu khun.
Ofloxacin, pefloxacin, ciprofloxacin: c ch nh trong nhim trng ti ch hay tng
qut gy bi cc chng nhy cm nh nhim trng mng no, xng khp, kh qun phi, ng tiu ha, ng tiu, sinh dc v tuyn tin lit.
Sparfloxacin, levofloxacin, moxifloxacin, gatifloxacin c hiu lc tt i vi nhim
trng phi mc phi cng ng v cn kch pht trong vim ph qun mn tnh;
trovafloxacin va alatrofloxacin l nhng dn cht mi, cho tc dng trn nhiu chng
khng thuc.
Tuy nhin, do c th gy hin tng chn lc ra cc chng khng, c bit vi S.
aureus v P. aeruginosae, nn mi trng bnh vin v trong trng hp b nhim vi
khun a khng phi s dng phi hp vi khng sinh khc (vancomycin,
Aminoglycosid, Cephalosporin III). Do , ch dnh s dng nhm khng sinh ny
trong cc trng hp nhim trng nng.
* Qua nhiu nm, cc nghin cu vn cha pht hin c c tnh ca cc Quinolon
trn s pht trin xng tr em, do hin nay ti nhiu nc loi khng sinh ny
c s dng thn trng trong mt s trng hp nhim trng nng, nguy him n
tnh mng tr em (th d: bnh vim no do nhim trng bnh vin tr s sinh,
nhim trng phi do bnh x ha nang, l cp tnh do Shigella) m cc thuc khc
khng c hiu qu.
Chng ch nh

Ph n c thai v cho con b.

Tr em di 15 tui (xem S dng tr liu).

Ngi thiu men G6PD (gluco - 6 phosphat dshydrogenase)

Ngi c bnh i tho ng vi gatifloxacin v cht ny c th gy tai bin do

lm tng hay gim ng huyt.

Thn trng

ngi thiu nng gan (vi pefloxacin v trovafloxacin)

ngi thiu nng thn (vi cc Quinolon khc) . Hiu chnh liu nu cn.

Phi trnh nh nng mt tri v chiu x tia t ngoi trong thi gian tr liu v 3
ngy sau khi dng sparfloxacin.

39

Tng tc thuc
Cc thuc khng acid lm gim hp thu cc Quinolon.
Phn ln cc Quinolon lm tng hot tnh ca warfarin, theophyllin do lm gim
thanh lc ca cc thuc ny.
Cimetidin lm gim chuyn ha cc Quinolon (nht l pefloxacin) v lm tng thi
gian bn thi
Khc vi cc Fluoroquinolon c trc, levofloxacin v sparfloxacin khng gy tng
tc vi theophyllin. Trovafloxacin cng khng tng tc dc ng ng k vi
cimetidin, theophyllin v warfarin.
Hiu lc ca cc Quinolon ng tiu b gim khi s dng cc cht acid ha nc
tiu v gia tng khi dng cc cht kim ha nc tiu.
ng s dng - Liu lng
Cc Quinolon I v norfloxacin dng bng ng ung. Cc Fluoroquinolon khc c
th s dng bng ng ung hay tim tnh mch chm.
Liu ngi ln: ( ngi c chc nng thn bnh thng)

Acid nalidixic (Negram) 1 - 2g/ ngy, chia 2 ln

Acid oxolinic (Urotrate) 1,5 mg/ ngy, chia 2 ln

Flumequin (Apurone) 1200 mg/ ngy, chia 3 ln

Rosoxacin (Eracine) 300 mg/ ngy, 1 ln duy nht

Pefloxacin (Peflacine) 0,8 - 1,6g/ ngy, chia 2 ln

Ciprofoloxacin (Ciflox) 0,5 - 1,5g/ ngy, chia 2 - 3 ln

Ofloxacin (Oflocet) 0,4 - 0,6g/ ngy, chia 2 ln

Norfloxacin (Noroxin) 0,8 - 1,5/ ngy, chia 2 ln ung

Sparfloxacin (Sparflo): 400 mg/ ngy, liu duy nht vo ngy u, 200 mg/ ngy
vo cc ngy k tip.

Levofloxacin (Levoquin):500 - 1000 mg/ ngy, dng trong 1 hoc 2 ln.

Gatifloxacin (Tequin): 200 - 400 mg (PO hay IV) dng 1 ln/ ngy.

Moxifloxacin (Avelox): 400 mg: ung 1 ln/ ngy.

40

Trovafloxacin (Trovan): 200 - 300 mg (IV); 200 mg (PO), 1 ln / ngy (ch dng t
7 - 14 ngy, khng nn dng khi c th thay th bng mt thuc hiu qu khc t
c tnh hn.

BI 5. SULFAMID V CC PHI HP
THUC C SULFAMID
MC TIU BI HC
1. K cc khng sinh tiu biu thuc nhm Sulfamid v cc phi hp c Sulfamid
thng c s dng trong iu tr nhim trng.
2. Gii thch c ch tc ng v nu c ch khng ca vi khun i vi cc
Sulfamid v cc phi hp c Sulfamid .
3. M t hat tnh khng khun, tnh cht dc ng hc, tc dng ph v c tnh
ca cc Sulfamid.
4. Nu cc ch nh tr liu, chng ch nh v tng tc thng gp ca cc khng
sinh trong nhm.
NI DUNG BI HC

1. SULFAMID
1.1. I CNG
Hin nay, nhm Sulfamid c s dng ch yu trong iu tr nhim trng ng tiu
v phi hp ca Sulfamid vi trimethoprim cng thng c dng trong iu tr
vim tai, vim kh qun, phi, vim xoang. S pht trin ca cc chng khng thuc
gii hn vic s dng Sulfamid vo cc mc ch tr liu khc.
Da trn vn tc hp thu v bi tit, c th phn loi cc Sulfamid nh sau:
Loi hp thu v thi tr nhanh:

Sulfisoxazol (Gantrisin)

Sulfamethoxazol (Gantanol)

Sulfadiazin (Adiazine)

Sulfamethizol (Rufol)

Loi hp thu chm, tc ng lng rut:

Sulfasalazin (Salazopyrine)

Sulfaguanidin (Entercin)

Loi s dng ti ch:

Sulfacetamid (Isoptocetamid)

Sulfadiazin bc (Silvadene)

Loi tc ng ko di (hp thu nhanh nhng thi tr rt chm)

Sulfadoxin (Thi gian bn thi: 100 - 230 gi)

41

1.2. HOT TNH KHNG KHUN

Cc Sulfamid c ph khng khun rng, tc ng trn nhiu vi khun Gram dng v
v Gram m, tuy nhin s khng ca vi khun vi Sulfamid pht trin nhanh trong
nhng nm gn y. Hiu lc ng k ca Sulfamid i vi mng no cu khun,
Shigella, E. coli c bit n trong nhiu nm, nay cng b khng r. Sulfamid ch
tc ng km khun.
1.3. C CH TC NG
Do c cu trc ha hc tng t vi para - amino benzoic acid (PABA) nn cc
Sulfamid i khng tng tranh vi PABA, ngn chn s dng PABA tng hp acid
folic ca vi khun. Ngoi ra, Sulfamid cn c hiu lc c ch dihidropteroat synthase
l men ca vi khun gip chuyn i PABA thnh dihydropteroic acid - cht trung gian
trong s tng hp acid folic. Sulfamid khng c hiu lc trn cc vi khun c th s
dng acid folic hay folat c sn. (Hnh 16.1).
H2N

SO2

NH2

H2N

Sulfanilamid

COOH

Para- amino- benzoic Acid

Pteridin +PABA

SULFAMID

Dihydropteroat syntase

Dihydropteroic acid
Glutamat
Dihydrofolic acid
NADPH
Dihydrofolat reductase (DHFR)
TRIMETHOPRIM
NADP
Tetrahydrofolic acid

Metylen tetrahydrofolat
Thymidilat, base purin, pyrimidin
DNA

Hnh a.1. S c ch tc ng ca Sulfamid v trimethoprim

1.4. C CH KHNG
S khng ca vi khun i vi Sulfamid l do t bin gen hay do plasmid v c
th dn n mt s bin i enzym chuyn ha PABA (dihydropteroat synthase), hay
s thay i kiu bin dng tng hp acid folic.
1.5. DC NG HC
Ngoi tr cc Sulfamid tc ng ngay ti rut, cc cht khc c hp thu nhanh qua
ng ung. S phn b thuc tt trong hu ht cc m v dch ngoi t bo, v thuc
42

qua c nhau thai. Sulfamid c chuyn ha mt phn gan thnh dng acetyl ha
mt hot tnh; c o thi ch yu qua ng tiu dng nguyn thy v dng
chuyn ha. Trong nc tiu acid, mt s Sulfamid kh ha tan v c th trm hin
dng tinh th, gy nghn ng tiu. Mt phn nh Sulfamid c bi tit vo mt,
sa...
1.6. TC DNG PH - C TNH
Phn ng nhy cm: ch yu da, mng nhy nh nga, ni mt, ban , hi chng
Stevens - Johnson, nhy cm vi nh sng...
c tnh vi mu:

Thiu mu tiu huyt: him xy ra (0,05 %)

Mt bch cu ht (0,1 %), c th hi phc khi ngng thuc.
Thiu mu khng ti to: him xy ra, do ty xng b c ch hon ton, thng
xy ra hn ngi b bnh AIDS hay c dng thuc loi c ch ty xng.

c tnh trn thn: s thnh lp cc tinh th trong nc tiu him xy ra i vi cc

Sulfamid loi thi tr nhanh. Tuy nhin, vn c th xy ra cho bnh nhn b mt nc
(bnh nhn AIDS dng sulfadiazin tr vim no do Toxoplasma). Cn ung
nc, hoc kim ha nc tiu gip Sulfamid d ha tan hn.
Cc phn ng khc: n mt ngon, bun nn, i ma (1 - 2 %), vim no tr s sinh
(do Sulfamid y bilirubin, gy tch t no)
1.7. TNG TC THUC
Quan trng nht l dng Sulfamid kt hp vi:

Cc thuc chng ng mu dng ung.

Thuc h ng huyt dng ung.

Thuc tr co git nhm hydantoin.

V Sulfamid lm tng hot tnh ca cc thuc ny, nguyn nhn c th do s c ch

chuyn ha thuc hay s y thuc ra khi kt hp vi albumin.
1.8. CH NH TR LIU V LIU LNG
Cc ch nh ngy cng gii hn:
Loi km hp thu: (sulfasalazin) dng tr vim lot kt trng (nhng d b ti pht).
Loi s dng ti ch: sulfacetamid, sulfadiazin bc c dng chng nhim trng mt
(dung dch sulfacetamid 10 - 30 %), nhim trng vt thng do phng (sulfadiazin
bc dng crem 10 mg).
Loi hp thu, thi tr nhanh: sulfisoxazol c a chung nht. Dng trong nhim
trng ng tiu, vim no do Toxoplasma (sulfadiazin phi hp vi pyrimethamin).
Ngoi ra cn c th dng trong bnh Nocardiose, Actinomycose.
43

Loi thi tr chm: sulfadoxin c phi hp vi pyrimethamin (Fansidar) trong iu

tr v phng nga st rt do P. falciparum khng vi mefloquin. Do mt s phn
ng ph nghim trng nh hi chng Stevens - Jonhsons..., thuc ch dng nga st
rt nu nguy c mc bnh do chng khng cao.
Liu lng ung:

Sulfasalazin (Salazopyrin): 2g/ ngy chia 3 - 4 ln

Sulfisoxazol (Gantrisin): 2 - 4g/ ngy chia 4 - 6 ln

Sulfadiazin (Adiazine): 100 mg/kg/ ngy chia 3 - 4 ln

Sulfamethizol (Rufol): 400 - 600 mg/ ngy, chia 3 - 4 ln

Trong bnh Toxoplasmose no ngi b AIDS, sulfadiazin c dng liu 4 - 6g/

ngy trong 6 tun, sau tip tc 2 - 3g/ ngy.

2. CC PHI HP C SULFAMID
S phi hp trimethoprim v cc Sulfamid l mt bc tin quan trng trong vic
pht hin cc cht khng khun c hiu lc tt. Hai cht ny tc ng hai giai on
khc nhau thuc qu trnh bin dng ca vi khun v dn n kt qu l s hip lc.
Dng phi hp thng gp nht l co - trimoxazol, l phi hp gia trimethoprim vi
sulfamethoxazol (Bactrim, Eusaprim, Cotrim). Ngoi ra cn c phi hp gia
trimethoprim vi sulfamoxol (Supristol) hay vi sulfadiazin (Antrima).
Phi hp ca pyrimethamin v Sulfamid c tc ng ko di (sulfadoxin) trong ch
phm FANSIDAR cng cho s hip lc nh trn, v c dng trong phng chng st
rt.
2.1. HOT TNH KHNG KHUN
Ph khng khun ca trimethoprim v sulfamethoxazol tng t nhau, tuy hiu lc
ca trimethoprim thng gp 20 - 100 ln sulfamethoxazol. Nhiu vi khun Gram
dng v Gram m nhy cm vi trimethoprim nhng s khng d pht trin khi
dng ring l cht ny. Cc vi khun khng vi sulfamethoxazol hay trimethoprim
dng ring l vn c th nhy cm vi phi hp ca hai cht. Tuy nhin, hiu lc ti
a ca co - trimoxazol t c khi vi khun nhy cm vi c hai thnh phn kt hp.
Vi mt s vi khun, s phi hp ny cho tc ng dit khun (trimethoprim cng tc
ng km khun khi dng ring nh Sulfamid)
2.2. C CH TC NG V KHNG
Trimethoprim (hay pyrimethamin) phi hp vi Sulfamid cho tc ng hip lc v
trimethoprim l cht c ch tng tranh dihydrofolat reductase, enzym gip s chuyn
i dihydrofolat thnh tetrahydrofolat. Vic s dng ng thi Sulfamid v
trimethoprim gy ra s c ch ni tip trong qu trnh tng hp acid folic, cht khng
th thiu trong s tng hp acid nucleic cho vi khun. (Hnh 16.1)
44

S khng ca vi khun vi co - trimoxazol pht trin chm hn so vi mi thnh

phn ring l. C ch khng thuc ging nh c ch khng cc Sulfamid.
2.3. DC NG HC
T l nng phi hp cho hot tnh tt nht ca trimethoprim v sulfamethoxazol
l 1/5. Trimethoprim c hp thu tt (> 95 %) bng ng ung nhng t l gn vi
protein huyt tng hi thp hn so vi sulfamethoxazol. Ch 10 - 15 % cht ny b
chuyn ha thnh cht v hot v trimethoprim c bi tit ch yu qua ng tiu
vi phn ln dng c hot tnh.
2.4. CH NH TR LIU CA CO - TRIMOXAZOL

Nhim trng ng tiu cp v mn tnh.

Nhim trng tuyn tin lit, vim t cung do lu cu khun.

Nhim trng phi, kh qun.

Nhim trng tai mi hng (thuc lun phin cho Macrolid v Beta - lactam)

Nhim trng ng tiu ha: thng hn, bnh do Shigella,...

Liu lng

Bactrim, Eusaprim (400 mg sulfamethoxazol + 80 mg trimethoprim): 2 vin x 2/

ngy.

Bactrim Fort, Eusaprim Fort (800 mg sulfamethoxazol + 160 mg trimethoprim): 1

vin x 2ln / ngy.

Antrima (400 mg sulfadiazin + 80 mg trimethoprim): 1 vin x 2 ln/ ngy.

Bactrim v Eusaprim cn dng dng tim bp v tim truyn IV.

2.5. TC DNG PH
Ging nh trng hp cc Sulfamid.

45

BI 6. THUC KHNG LAO PHONG

MC TIU BI HC
1. Trnh by v phn bit cc thuc lao thuc nhom thuc khng lao tuyn u v
tuyn th hai.
2. M t hot tnh khng khun, c ch tc ng, tnh cht dc ng, tc dng ph
v c tnh ca cc thuc khng lao.
3. Nu c tm quan trng v cc nh ngha v khng ca vi khun i vi
thuc khng lao
4. Trnh by v s dng tr liu thuc khng lao qua mt s phc tr lao ph bin.
5. Trnh by v cc thuc chnh dng trong phc iu tr phong.
NI DUNG BI HC

1. THUC KHNG LAO

Bnh lao ngi gy bi vi khun chnh l Mycobacterium tuberculosis, trc khun
khng acid vi thnh t bo giu lipid. Cc Mycobacterium l vi khun ni t bo,
phn chia rt chm (khong 20 gi). Vic iu tr bnh lao lun i hi s phi hp
nhiu loi thuc nhm trnh s chn lc cc chng khng. Cc thuc khng lao
khng hp thnh nhm c cu trc ha hc tng t, do trn thc t s phn loi
cc thuc ny c da trn hot tnh khng khun ca chng. Hin nay cc thuc
khng lao c chia thnh hai nhm:
Cc thuc khng lao hng th nht (first - line drugs) trong rifampicin v
isoniazid l 2 thuc chnh yu v cc thuc cn li l thuc c dng phi hp:

Rifampicin = rifampin (Rifadine, Rimactan)

Isoniazid = INH (Rimifon, Nydrazid)

Ethambutol (Myambutol)

Pyrazinamid (Pyrilene)

Streptomycin (Streptomycine)

Cc thuc khng lao hng th hai (second - line drugs): l nhng thuc c hiu lc
km hn thuc hng th nht, c tnh cao hn hoc cha c nghin cu rng ri v
tc ng khng lao. Cc thuc ny c li ch i vi bnh nhn khng dung np c
thuc hng th nht hay khi b nhim bi vi khun lao khng thuc hng th
nht, gm c:

P - aminosalicylic acid (PAS)

Capreomycin

46

Cycloserin

Ethionamid

Fluoroquinolon

Macrolid

1.1. CC THUC KHNG LAO HNG TH NHT

1.1.1. Hot tnh khng khun
Ngoi tr ethambutol c xem l cht km khun, cc thuc khng lao khc c tc
ng dit khun. Ring isoniazid ch c tc ng dit khun khi vi khun ang phn
chia v tc ng km khun trng thi ngh ca vi khun. Khc vi isoniazid,
ethambutol v pyrazinamid, rifampicin v streptomycin cn tc ng hu hiu trn
nhiu vi khun Gram m v Gram dng khc nh Pseudomonas, E. coli, Klebsiella,
Staphylococcus, H. influenzae, streptomycin khng vo c bn trong t bo nn
khng dit tn gc c vi khun lao.
C ch tc ng

Rifampicin: c ch RNA - polymerase ca vi khun.

Isoniazid: c ch s tng hp acid mycolic mng t bo vi khun.

Ethambutol: c ch s tng hp RNA ca vi khun hoc ngn s st nhp ca acid

mycolic vo mng t bo vi khun.

Pyrazinamid: c th do tc ng trn s iu ha NAD

Streptomycin: c ch s tng hp protein ca vi khun.

S khng thuc
S khng ca vi khun lao xy ra nhanh chng khi s dng ring l rifampicin,
isoniazid, pyrazinamid v chm hn i vi ethambutol, streptomycin.
C ch khng: cha c chng minh y .

Isoniazid: do t bin gen lin quan n s sinh tng hp acid mycolic vi khun.

Rifampicin v streptomycin: do s t bin lm thay i im tc dng ca thuc

vi khun.

Cng b ca T chc Y T th gii (WHO) u nm 2008 cho bit t l nhim lao

khng nhiu thuc (MDR - TB) hin mc cao ng lo ngi. Ngoi ra, xut hin
lao khng thuc cc mnh (XDR - TB hay EDR - TB), y l mt dng lao gn nh
khng cha lnh c).

47

Ch thch
* MDR - TB (multi - drug - resistant tuberculosis): l lao khng t nht vi 2 thuc
chng lao tt nht, rifampicin v isoniazid. Nhng thuc ny c xem l thuc hng
th nht v dng cho tt c bnh nhn iu tr lao.
* XDR - TB hay EDR - TB: (extensively - drug - resistant tuberculosis): l lao ngoi
khng vi rifampicin v isoniazid, cn khng vi bt k thuc Fluoroquinolon no
v t nht vi mt trong 3 thuc dng tim thuc nhm khng lao hng th hai gm
capreomycin, amikacin v kanamycin (hoc streptomycin)
1.1.2. Dc ng hc
Ngoi tr streptomycin phi s dng bng ng tim chch (thng tim bp) cc
thuc khng lao k trn u c hp thu tt bng ng ung.
Cc thuc c phn b tt cc m trong c th.
Rifampicin: cn phn tn trong cc dch c th k c dch no ty (LCR). Thuc c
th nhum cam phn v cc dch sinh l nh nc tiu, nc bt, nc mt, m
hi, Thuc c bi tit nhanh chng vo mt dng kh acetyl cn gi nguyn
hot tnh khng khun v c chu k gan rut. Do rifampicin gy cm ng men gan,
vn tc kh acetyl ca cht ny gia tng v thi gian bn thi ca thuc gim dn sau
14 ngy tr liu. Khong 30 % rifampicin c bi tit vo nc tiu v 60 - 65 % vo
phn.
Isoniazid (INH): phn b tt vo m, dch c th v c bn trong t bo. c chuyn
ha gan v bi tit vo nc tiu (75 - 95 %). Sn phm chuyn ha chnh l kt qu
ca s acetyl ha v s thy phn bi enzym. Vn tc acetyl ha lm thay i ng k
nng INH trong huyt tng cng nh thi gian bn thi ca thuc ny.
Streptomycin (xem phn Nhm Aminoglycosid)
Ethambutol: c bi tit phn ln qua thn dng khng chuyn ha.
Pyrazinamid: bi tit qua thn sau khi b thy phn v hydroxyl ha.
1.1.3. Tc dng ph c tnh - Chng ch nh
Rifampicin

D ng (4 % bnh nhn) ban da, st, bun nn, nn ma.

c tnh trn gan, nht l khi dng phi hp vi INH hay pyrazinamid hay ngi
c bnh gan.

c tnh trn thn v mu.

L cht gy cm ng men gan mnh, lm gim tc ng ca nhiu thuc nh:

digitoxin, quinidin, ketoconazol, propranolol, methadon, corticosteroid, theophyllin,
cht khng ng mu dng ung, thuc ung nga thai, barbiturat

Chng ch nh: thiu nng gan v thn.

48

Isoniazid

D ng, st, ban da, nga.

c tnh trn gan: vim gan cp, nht l khi dng chung vi cc cht gy cm ng
men gan nh rifampicin hay khi b thiu nng gan.

c tnh thn kinh: vim dy thn kinh ngoi bin, co git, vim dy thn kinh mt.
C th lm gim c tnh trn thn kinh bng cch dng phi hp vi pyridoxin
liu thp.

Chng ch nh: bnh gan v cc bnh v thn kinh.

Ethambutol

Vim dy thn kinh mt: thng xy ra v rt nng.

D ng (him): ni mt da, au u, chng mt.

Tiu ha: au bng, n khng ngon, bun nn.

Pyrazinamid

c tnh trn gan: xy ra 15 % bnh nhn vi liu ung 3g mi ngy. Cn ngng

thuc khi c du hiu tn thng gan.

Chng ch nh ngi thiu nng gan.

Streptomycin

c tnh trn thn

c tnh trn thnh gic.

1.2. CC THUC KHNG LAO HNG TH HAI

y l cc thuc c th dng thay th cho thuc nhm hng th nht trong trng hp
iu tr lao khng nhiu thuc (MDR - TB), lao khng thuc ph rng (XDR - TB) hay
trng hp nhim vi khun lao khng in hnh (M. avium, M. xenopi) bnh nhn
HIV.
Acid aminosalicylic (PAS): ngy nay t c s dng do kh nng hp thu km. y
l cht km khun tc ng bng cch c ch tng tranh vi acid para aminobenzoic
(PABA) trong s tng hp folat vi khun.
Capreomycin: l mt peptid c tc dng c ch s tng hp protein vi khun, c s
dng bng ng tim chch. Capreomycin l thuc c u tin dnh cho vic iu
tr lao a khng thuc (MDR). Cn theo di tr liu phng nga c tnh trn thn
v thnh gic.
Cycloserin: c hiu lc qua ng ung, tc dng bng c ch s tng hp thnh vi
khun. c phn b tt trong cc dch c th, k c dch no ty. Thuc c bi tit
vo nc tiu th nguyn vn v dng chuuyn ha, c th tch t ngi suy thn.
49

Tc dng ph gm xo trn thn kinh trung ng, bnh l v thn kinh ngai bin
cng c th xy ra, nhng p ng vi pyridoxin (vitamin B6).
Ethionamid: c cu trc tng t isoniazid nhng c th khng tc dng vi cng c
ch. Cht ny c th c ch s acetyl ha isoniazid. c s dng bng ng ung
v phn b khp c th, k c dch no ty. Thuc c chuyn ha v thi tr ch yu
qua ng tiu Cc tc dng ph c th gii hn vic dng thuc l kch ng d dy,
bnh l thn kinh ngai bin v vim dy thn kinh th gic. Vic dng b sung
vitamin B6 c th gim bt c tnh trn thn kinh.
Fluoroquinolon: nh ciprofloxacin v levofloxacin c v tr quan trng trong iu tr
lao khng nhiu thuc. Mt s chng Mycobacterium khng in hnh cng nhy cm
vi cc thuc ny.
Macrolid: nh azithromycin v clarithromycin, l thnh phn phi hp vi
ethambutol v rifabutin trong iu tr M. avium ni t bo. Azithromycin c chn
dng cho bnh nhn HIV v thuc ny khng nh hng n s chuyn ha ca cc
ARV (thuc khng HIV).
1.3. S DNG TR LIU
Nhm ngn nga s pht trin khng cc thuc khng lao, vic iu tr phi gm t
nht 3 thuc m vi khun lao cn nhy cm trong giai on tn cng.
1.4. CC PHC TR LIU THEO WHO 2008
Trc khi c rifampicin, vic iu tr lao phi ko di 12 thng phng ti pht
bnh. Ngy nay, phc tr lao vi rifampicin thng p dng l 6 thng v trong giai
on u c th dng kt hp 3 hay 4 thuc. Theo OMS, phc ha tr liu ngn
ngy c nhiu thun li cho bnh nhn, m ha vi khun nhanh v t l ti pht thp.
Phc tr liu c s quan st trc tip ca cn b y t (DOT= Directly Observed
Therapy) ko di t 6 - 8 thng.
Phc cho lao mi, lao ngi b HIV nng: 6 - 8 thng
2 HRZE/ 4RH hay 2 HRZE/ 6HE

2 thng u: Rifampicin + INH+ PZA+ Ethambutol (hay streptomycin)

4 thng k: Rifampicin + INH hay 6 thng k: INH + Ethambutol

Thuc c th s dng hng ngy hoc 3 ln/tun .

Ghi ch:
S = streptomycin; R= rifampicin; H = INH hay isoniazid;
E= ethambutol; Z = PZA hay pyrazinamid.

50

Phc cho lao ti pht, khng p ng thuc hay iu tr b gin on: 8 thng
2 SRHZE / 1RHZE/ 5 R3H3E3

2 thng dng 5 thuc SHRZE,

1 thng 4 thuc HRZE,

5 thng 3 thuc RHE (dng thuc 3 ln mi tun)

Phc iu tr lao khng nhiu thuc (MDR - TB)

S la chn thuc trong phc thng phi c th ha, da vo nhy cm vi
khng sinh, ch thuc iu tr trc , tnh trng sc khe bnh nhnNn dng
cc thuc thuc hng th nht cn nhy cm phi hp vi 1 khng sinh nhm
Fluoroquinolon, 1 khng sinh nhm Aminoglycosid v thuc thch hp thuc hng th
hai.
Nguyn tc iu tr: bt u vi 4 - 6 thuc cha dng trc y. Thuc tim s ngng
sau vi thng nu thch hp v cc thuc kh dung np s b loi dn. Tuy nhin, bnh
nhn phi hon tt iu tr vi t nht 3 thuc c chng minh cn nhy cm trn
khng sinh . Thi gian iu tr: t 18 - 24 thng (theo ATS, American Thoracic
Society). Bnh nhn MDR - TB phi vo bnh vin trnh ly lan trong thi gian u
v c kim sot trc tip (DOT).
i vi bnh lao khng vi thuc hng th nht v nhiu thuc ca hng th hai (XDR
- TB) th phi s dng nhiu loi thuc m vi khun lao cn nhy cm (c th xem nh
thuc hng th ba) nh: linezolid, - interferon, - lactam (imipenem, amoxicillin clavulanat) vi liu cao v ko di nu bnh nhn c th dung np.
Phc iu tr lao do nhim mycobacterium khng in hnh.
Cc Mycobacterium khng in hnh (th d: M. avium, M. xenopi) thng
khng vi cc thuc khng lao c in. Cch y hn 10 nm, cc trng hp nhim
trng loi ny t xy ra (thng l nhim trng phi, hch, da) nhng gn y t l
bnh gia tng cng vi s xut hin ca bnh AIDS v ng hng th 3 trong cc bnh
nhim trng c hi nhng bnh nhn b bnh AIDS. Bnh ch yu do
Mycobacterium avium ni t bo gy ra. Cc thuc thng c dng phi hp tr
liu l cc thuc lao hng th hai:
- Amikacin

- Clofazimin

- Cycloserin

- Rifabutin

- Fluoroquinolon (ofloxacin, ciprofloxacin)

- Clarithromycin

Tuy nhin cc kt qu tr liu thng khng chc chn.

51

Liu lng
Cc thuc c dng ung mt ln trong ngy, lc i, ngoi tr cycloserin,
ethionamid, PAS do s lng ln phi chia lm 2 ln/ ngy.
- Isoniazid: 5 mg/kg/ ngy; 10 mg/kg 3 ln/tun
- Rifampicin: 10 mg/kg/ ngy hay 3 ln/tun (liu ti a 600 mg/ng)
- Ethambutol: 15 mg/kg/ ngy; 30 mg/kg 3 ln/tun
- Pyrazinamid: 25 mg/kg/ ngy ; 35 mg/kg 3 ln/tun
- Streptomycin: 15 mg/kg/ ngy hay 3 ln/tun, cn gim liu ngi suy thn.
1.5. PHC TR LIU TRONG NC
Hin nay, ti Vit Nam bnh nhn lao c iu tr theo hng dn ca CTCLQG
(Chng trnh chng lao quc gia) vi nhng phc tng t phc chun ca
WHO:
Lao mi pht hin 8 thng tr liu: 2SRHZ/ 6HE
- 2 thng tn cng vi 4 loi thuc SRHZ (c th thay streptomycin = ethambutol)
- 6 thng tip theo: 2 loi thuc HE
Lao ti pht: 2SHRZE/ 1HRZE/ 5R3H3E3 (R3: rifampicin dng 3ln/tun)
- 2 thng dng 5 thuc SHRZE
- 1 thng 4 thuc HRZE
- 5 thng 3 thuc RHE

2. THUC IU TR PHONG
Bnh phong gy bi vi khun Mycobacterium leprae. Theo khuyn co ca T chc Y
T th gii (WHO) th iu tr phong hin nay phi l a tr liu vi s phi hp nhiu
thuc nhm trnh s khng thuc nhanh chng. Ba thuc chnh dng trong phc tr
phong hin nay l dapson, clofazimin v rifampicin. Mt s thuc khc c th dng
trong iu tr phong l ethionamid, thalidomid..
Dapson, DDS (Disulone)
Dapson c cu trc tng cn cc Sulfamid v c tc dng km khun i vi
Mycobacterium leprae, tuy nhin cc chng khng thuc xut hin.
C ch tc dng: tng t cc Sulfamid, i khng PABA dn n c ch tng hp
acid folic.
Dapson c hp thu tt qua ng tiu ha v c phn b khp c th, t nng
cao da. Dng thuc nguyn thy c chu k gan rut v c acetyl ha gan. Dng
nguyn thy v cht chuyn ha u c thi tr qua nc tiu.
52

Tc dng ph bao gm thiu mu tiu huyt, c bit d xy ra ngi b thiu men

G6PD (glucose - 6 - phosphat deshydrogenase), ri lon tiu ha, bnh l thn kinh
ngoi bin, v c th lm pht sinh cc nt sn l phn ng tin trin nghim trng
da trong bnh phong (ENL:Erythema Nodosum Leprosum), c th iu tr bng
thalidomid hay d phng bng clofazimin.
Clofazimin (Lamprene)
L cht loi phm mu phenazin, c tc ng dit khun i vi Mycobaterium leprae
v cng c mt phn hiu lc trn M. avium ni t bo. Thuc cn c hiu lc khng
vim do hn ch s to cc nt sn da.
C ch tc dng: gn kt vo phn t DNA ca vi khun v ngn cn s ti bn DNA.
Ngoi ra, cht ny c th to cc gc oxy c c tnh vi t bo v c vi vi khun.
Hp thu qua ng tiu ha, thuc c tch ly m, cho php tr liu khng lin
tc, tuy nhin khng qua c thn kinh trung ng.
Tc dng ph: c th lm da c mu nu v gy vim rut.
Rifampicin: cn c tc dng dit trc khun lao mnh v nhiu vi khun khc. Trong
iu tr phong, thng c dng phi hp vi cc thuc khc. Xem chi tit hn
phn Thuc khng lao.
Ethionamid: thuc khng lao, c th dng thay th clofazimin trong iu tr phong,
ung vi liu 250 - 375 mg/ ngy. Xem chi tit hn phn Thuc khng lao
Thalidomid: Khng c tc dng trn trc khun lao nhng c hiu qu r rt trn th
phn ng da nng ca bnh phong (ENL), lm h st, gim au v cc nt sn vi liu
100 mg x 3 - 4 ln/ ngy trong 1 tun, sau gim dn cn 25 - 100 mg/ ngy (dng
phi hp vi thuc khng lao). Nn nh, y l thuc c th gy qui thai nn cn c
s kim sot cht ch khi ch nh thuc cho ph n. Ngoi ra, tc dng ph thng
gp l bun ng, to bn v bnh l thn kinh ngai bin.
PHC IU TR PHONG (WHO)

DDS: 100 mg/ ngy

Clofazimin: 50 mg/ ngy

Rifampicin: 600 mg mt ln/thng (c gim st).

Cc thuc c dng bng ng ung. Thi gian iu tr t 6 - 24 thng ty theo tnh

trng bnh v phi c s theo di xt nghim vi khun nh k cng nh theo di cc
phn ng ph. Nn c s phi hp ha tr liu v vt l tr liu hn ch hu qu tn
ph .

53

3. CC NHM KHNG SINH KHC

Bng 1.1. Cc nhm khng sinh khc
CC NHM KHNG SINH
V CHT TIU BIU

PH KHNG KHUN

CH NH
TR LIU CHNH

C CH TC NG
V S KHNG

TC DNG PH
- C TNH

FOSFOMYCIN
Fosfomycin (Fosfocine)

Staphylococcus (c meti - R) Nhim trng nng: xng

khp, mng no, phi gy
Trc khun Gram ( - ):
bi cc chng khng, nht
- Vi khun h khun ng l Staphy.
rut.
Lun lun phi hp vi:
- Pseudomonas aeruginosa. Beta - lactam/
Aminoglycosid/ Quinolon/
rifampicin.

Fosfomycin Trometanol

Vi khun Gram (+) v( - ) gy Liu ung duy nht 3g ( 50 Nh trn

nhim trng ng tiu.
mg/kg) tr vim bng quang
cp tnh th khng phc tp
ngi ph n cn tr.

Ri lon tiu ha, da.

ACID FUSIDIC

Ph hp:

Xo trn tiu ha

Acid fusidic

Staphylococcus: meti - S v
meti - R.

(Uridose, Monuril)

(Fucidine)

Vi khun k kh Gram (+)

Clostridium.

54

Ch yu dng tr nhim
trng nng do t cu khun.
Vim rut kt mng gi

c ch enzym pyruvyl Tiu chy

transferase trong giai on
u ca s tng hp Tng transaminase
peptidoglycan.
Dng IV: 1g Fosfomycin
khng do t bin nhim cha 0,33gNa, do cn
gim liu ngi suy thn,
sc th.
ph, suy tim.

c ch s tng hp protein
ribosom.

Vng da (nh)

khng do t bin nhim

Cn gim liu ngi suy
sc th.
Lun lun dng phi hp vi
gan.
khng sinh khc.

LINCOSAMID
Lincomycin (Lincocine)
Clindamycin (Dalacine)
IM, PIV, gel.
POLYPEPTID
Polymyxin E = Colistin
(Colimycine)
Polymyxin B

Ph hp
Staphylococcus
Streptococcus
Vi khun k kh Gram ( - )
(Bacteroides fragilis)
Ph hp, gm mt s trc
khun Gram ( - ): E. coli,
Klebsiella, Shigella,
Salmonella, H. influenza,
Enterobacter,
Pseu.aeruginosa.

(Polymyxine B)
Bacitracin A

Ph gn ging ca penicillin

Tyrothricin (Ricridene)

Cc trc khun Gram (+)

Lincomycin: nhim trng do

Staphylococcus, nht l
xng khp (tr vim mng
no).

c ch tng hp protein
ribosom 50S.
khng thu nhn
(plasmid).

Ri lon tiu ha
D ng
Gim bch cu ht

Clindamycin: nhim trng do

vi khun k kh (Bacteroides)
tr mng no.

Vim rut kt mng gi

Tim chch (ngoi l): nhim Lm thay i tnh thm

trng nng do trc khun
chn lc ca mng t bo
Gram ( - ), Pseudomonas
vi khun do gy ri lon
cu trc.
Ung (ngoi l) vim d dy
rut
khng t nhin l ch
yu. t c khng thu
Ti ch: thuc m, dung dch
nhn.
Ch s dng ti ch do c
tnh qu cao

c tnh trn thn cao (20 %)

khi dng tim chch
c tnh thn kinh: d cm,
o gic, xo trn th gic
D ng (him)

55

CU HI N TP phn khng sinh khng khun:

1. iu no khng ng i vi s khng khng sinh c ngun gc plasmid
A.

L s khng c tn sut cao.

B.

Xy ra i vi nhiu nhm khng sinh khc nhau.

C.

Chim 80 - 90 % cc trng hp khng.

D.

khng pht sinh do cm ng vi khng sinh.

E.

Tnh khng di truyn theo chiu dc cho cc vi khun cng h.

2. Khng sinh c xem l c hiu lc dit khun ph thuc thi gian

A.

Imipenem

B.

Ampicillin

C.

Neomycin

D.

Streptomycin

E.

Ciprofloxacin (trn Gram m)

3. c ch s tng hp protein l c ch tc ng ca
A.

Ceftazidim

B.

Chloramphenicol

C.

Piperacillin

D.

Sulbactam

E.

Mt khng sinh khc.

4. Khng sinh c xem l c hiu lc trn cc mm a khng l

56

A.

Tobramycin

B.

Rifampicin

C.

Clindamycin

D.

Amikacin

E.

Aztreonam

5. au khp, c, tn thng gn Achill l tc dng ph c bit xy ra khi tr liu ko

di bng khng sinh no sau y
A.

Doxycyclin

B.

Erythromycin

C.

Amikacin

D.

Norfloxacin

E.

Lincomycin

6. Cht c hiu lc mnh nht trong cc cyclin

A.

Chlortetracyclin

B.

Doxycyclin

C.

Minocyclin

D.

Tetracyclin

E.

Oxytetracyclin

7. Cephalosporin th h III c s dng bng ng ung l

A.

Ceftriazon

B.

Cefotaxim

C.

Latamoxef

D.

Ceftazidim

E.

Cefpodoxim

8. Khng sinh no khi s dng n c d chn lc ra cc chng khng do t bin

nhim sc th
A.

Gentamicin

B.

Fosfomycin

C.

Lincomycin

D.

Paromomycin

E.

Doxycyclin

57

9. S phi hp 2 loi khng sinh no di y s gy ra hiu lc i khng

A.

Penicillin v gentamicin

B.

Trimethoprim v sulfamethoxazol

C.

Erythromycin v ampicillin

D.

Rifampicin v fosfomycin

E.

Vancomycin v amikacin

10. Khng sinh c hiu lc trn trc khun m xanh do bn vng vi men
Cephalosporinase
A.

Meticillin

B.

Bacampicillin

C.

Ticarcillin

D.

Oxacillin

E.

Mt khng sinh khc

11. Thuc khng lao c tc ng gy cm ng men gan mnh

A.

Isoniazid

B.

Ethambutol

C.

Pyrazinamid

D.

Rifampicin

E.

Streptomycin

12. Nhum mu cam cc dch sinh l ca bnh nhn l c im ca loi thuc

khng lao no sau y

58

A.

Streptomycin

B.

INH

C.

Pyrzinamid

D.

Ethambutol

E.

Rifampicin

13. Cc thuc khng lao sau y u c c tnh trn gan, ngoi tr

A.

INH

B.

Streptomycin

C.

Rifampicin

D.

Pyrazinamid

E.

B v D ng

14. Loi sufamid c s dng ti ch l

A.

Sulfadoxin

B.

Sulfisoxazol

C.

Sulfamethizol

D.

Sulfamethoxazol

E.

Sulfacetamid

15. c xp vo loi thuc khng lao hng th hai :

A. Isoniazid

D. Pyrazinamid

B. Ethambutol

E. Capreomycin

C. Isoniazid
16. Khng sinh Fluoroquinolon c hiu lc tt trong nhim trng phi mc phi
cng ng:
A. Pefloxacin

D. Ciprofloxacin

B. Ofloxacin

E. Mt loi khc

C. Moxifloxacin
17. Cc thuc sau y c hiu lc trn trc khun lao, ngoi tr:
A. Dapson
B. Clofazimin
C. Rifampicin
D. Thalidomid
E. Ethionamid.
18. Gii thch v tc ng hip lc ca hai thnh phn trong co - trimoxazol

59

CHNG 4. THUC KHNG NM, KHNG VIRUS

BI 7. THUC KHNG NM
MC TIU BI HC
1. K cc cht tiu biu v thng c s dng trong iu tr nhim nm tan thn
v nm ti ch.
2. Trnh by ph khng nm, c ch tc ng ca thuc v nu c ch khng ca
t bo nm i vi thuc.
3. M t v dc ng hc, tc dng ph v c tnh ca mi loi thuc khng nm.
4. Nu ch nh tr liu v chng ch nh cng nh cc tng tc thuc quan trng
ca thuc khng nm.
NI DUNG BI HC

1. I CNG
iu tr cc bnh nhim nm, ngi ta dng cc thuc khng nm. l cc khng
sinh c hiu, khng c tc ng trn vi khun v mi loi c mt ph khng nm nht
nh.
Da trn s phn bit hai th bnh: nhim nm tan thn v nhim nm b mt, cc
thuc khng nm cng c chia thnh hai loi: thuc khng nm ng ton thn v
loi s dng ti ch. Tuy nhin, s phn chia ny ch c tnh tng i v mt s thuc
khng nm nh amphotericin B, cc dn xut imidazol v triazol c th c s dng
cho c hai mc ch tr liu.
Cc thuc khng nm c th c ngun gc sinh hc (nh amphotericin B, nystatin,
griseofulvin) hay c tng hp ha hc (flucytocin, cc dn xut imidazol v triazol).

2. THUC KHNG NM TON THN

2.1. AMPHOTERICIN B
Amphtericin B (Fungizone, Ambisome) c ly trch t nm Streptomyces nodosus
(1956), l cht thuc nhm khng sinh polyen Macrolid.
Hot tnh khng nm
Ph khng nm ca amphotericin B rng, bao gm cc nm Candida, Cryptococcus,
Blastomyces, Histoplasma, Coccidioides, Aspergillus.

60

C ch tc ng v s khng ca nm
Amphotericin B gn vo ergosterol c trong mng t bo nm, lm gia tng tnh thm
ca mng, khin mt s phn t nh bn trong t bo b thot ra ngoi v nm b hy
hoi. Mt c ch khc l s oxy ha lm h hi t bo nm.
S khng ca nm vi amphotericin B him xy ra, c th do s t bin gen, thay
th ergosterol bng cc tin cht ca sterol.
Dc ng hc
Amphotericin B hp th rt km qua ng ung, do thng c dng bng
ng tnh mch. Cht ny qua dch no ty cng rt km ( tr vim mng no do
nhim nm, c th tim qua ty sng hay no tht bn). Vo c th, amphotericin B
c gn gi mnh cc m, nht l m gan, t tng sau thn v phi. c thi
tr rt chm, ch yu qua mt.
Tc dng ph c tnh
Phn ng cp tnh: thng xy ra trong hai gi u khi tim amphotericin B l au
u, st, n lnh, i khi dn n h huyt p, try tim mch. phng nga, c th
s dng trc thuc khng histamin hay corticoid v thuc h nhit (paracetamol).
c tnh trn thn: Kh thng xuyn nht l khi s dng liu cao hoc ko di hay
c dng ng thi vi cc thuc c c tnh vi thn (Aminoglycosid,
cyclosporin). Nu khng ngng kp thi, s gy tn thng thn khng hi phc.
c tnh trn mu: thiu mu, gim tiu cu, gim bch cu ht c th xy ra, hi phc
chm khi ngng tr liu.
Cc tc dng ph khc: bun nn, nn ma, gim cn, vim tnh mch huyt khi ni
tim.
S dng tr liu:
Do s km dung np v c nhiu c tnh nn amphotericin B c s dng gii hn
trong iu tr bnh nhim nm ton thn bng ng tim tnh mch (IV). Ngoi ra
amphotericin B cn c dng bng ng ung tr nhim Candida rut v di
dng ti ch iu tr bnh ngoi da v nm ming do Candida.
Liu IV: 0,5 0,6 mg/kg trong dung dch glucose 5 %. Tim truyn rt chm (8 - 10
gi) v cch nhau 48 gi.
Ngoi dng c in, amphotericin B cn c bo ch vi cng thc c lipid nh dng
phc hp lipid (Abelcet, 1996), dng bao bi mng liposom c ng knh < 100nm
(Ambisome, 1997) hay dng phn tn keo (Amphotec, 1996). Cc dng mi ny (IV)
c th gp thuc d dung np hn v gim c tnh thn.

61

2.2. GRISEOFULVIN
Griseofulvin (Grisefuline, Fulcine) c trch ly t Penicillum griseofulvium, l dn
cht benzohydrofuran.
Hot tnh khng nm
Griseofulvin ch c hot tnh trn cc loi nm da (dermatophytes): Microsporum,
Epidermophyton v Tricophyton (gy bnh nm da, tc, mng).
C ch tc ng:
Griseofulvin c ch s gin phn ca t bo nm.
Dc ng hc
Griseofulvin c hp thu qua ng tiu ha tng i tt nhng khng ng u
i vi tng c th. S hp thu gia tng khi thuc c dng trong ba n c nhiu
cht bo. Thuc c phn tn ch yu trong cht sng da, tc, mng. Sau khi
chuyn ha gan, griseofulvin c thi tr chm qua ng tiu (50 %).
Do gy cm ng men microsom gan, griseofulvin c th lm gim tc ng ca thuc
nga thai dng ung v b gim hp thu ng tiu ha khi dng ng thi vi cc
barbiturat.
Tc dng ph
D ng da v nhy cm vi nh sng.
Ri lon tiu ha khi dng ko di.
Ri lon thn kinh: chng mt, nhc u, bun ng.
Him khi xy ra ri lon v mu (thiu mu, gim bch cu).
Chng ch nh: ph n c thai.
S dng tr liu: Tt c cc bnh nm da, tc, mng.
ng ung: 0.5 1g/ ngy, c th n 2g/ ngy trong trng hp nng, chia 3 - 4 ln.
Tip tc vic iu tr cho n khi ni b nhim xut hin tc, mng hay da bnh
thng.
Dng ti ch: pommade bi ngoi da.
2.3. FLUCYTOSIN: 5 - FLUOROCYTOSIN
Flucytosin (Ancotil) l thuc khng nm tng hp c s dng tr liu t nm 1967,
c cu trc tng t vi cytosin.
Hot tnh khng nm:
Ph khng nm ca flucytosin hp, c hot tnh cao trn cc nm Candida,
Cryptococcus, Torulopsis v tc ng yu hn trn Aspergillus.
62

C ch tc ng
Sau khi xm nhp t bo nm, 5 - fluorocytosin c bin i thnh 5 - fluorouracil
di tc dng ca men desaminase, 5 - fluorouracil l mt cht chng chuyn ha
mnh, c tc dng c ch s tng hp DNA v s tng hp protein ca nm. Tc ng
ny chuyn bit v t bo ngi khng c men chuyn i 5 - fluorocytosin thnh
5 - fluorouracil.
S khng ca nm
S khng xy ra khi s dng fluocytosin n tr. Do , thng s dng phi hp
flucytosin vi amphotericin B. y l mt phi hp ng vn. Nguyn nhn gy
khng c th do s gim tc ng ca cc enzym chuyn ha flucytosin.
Dc ng hc
Flucytosin c hp thu tt bng ng ung, phn b rt tt cc m, k c dch no
ty (nn c dng tr vim mng no). Thuc c thi tr qua thn dng c hat
tnh, do cn gim liu flucytosin ngi suy thn.
Tc dng ph
Xo trn tiu ha: bun nn, tiu chy, vim rut.
Xo trn mu: mt bch cu ht, gim tiu cu do flucytosin c th gy suy ty.
Xo trn cc enzym gan.
S dng tr liu
c dng iu tr cc trng hp nng do nhim Candida hay Cryptococcus nh
vim mng no, nhim nm ni tng, Phi s dng kt hp flucytosin vi mt
thuc khng nm ton thn khc, thng dng amphotericin B vi liu 0.3 mg/kg/
ngy.
Liu ung: 100 - 150 mg/kg ngy chia 4 ln, cn hiu chnh liu ngi suy thn.
2.4. CC DN XUT IMIDAZOL V TRIAZOL
y l cc cht khng nm tng hp, c s dng tr liu t u thp nin 1970. C
rt nhiu dn xut imidazol v triazol nhng ch mt s cht c tc ng khng nm
tan thn. l miconazol, ketoconazol (imidazol) v fluconazol, itraconazol (triazol).
Cc cht ny c cng ph khng nm v c ch tc ng.
Hot tnh khng nm
Ph khng nm rng, gm cc nm Candida, Cryptococcus, Blastomyces,
Histoplasma, Coccidioides, Aspergillus v cc nm ngoi da.
C ch tc ng
nng cho tc dng ton thn, cc dn xut imidazol v triazol ch yu c ch h
enzym cytochrom P-450 ca t bo nm, lm ngn cn s kh metyl 14 63

metylsterol, l tin cht ca ergosterol. S thiu ht tng hp ergosterol v tch t cc

14 - metylsterol mng t bo nm lm c ch s tng trng ca nm.
S khng ca nm
Cc chng Candida khng vi nhng dn xut azol c tm thy cc bnh nhn
AIDS. Nguyn nhn khng c th do s gia tng sn xut enzym kh metyl hay lm
thay i enzym ny. Thng c s khng cho gia cc dn xut azol.
2.4.1. Ketoconazol
Dc ng hc
S hp thu bng ng ung ca ketoconazol mc trung bnh. Do cn mi trng
acid ha tan, sinh kh dng ca ketoconazol b gim khi dng ng thi vi cc
cht khng acid hay c ch tit acid (cimetidin, ranitidin).
Ketoconazol phn tn nhanh trong c th, ngoi tr dch no ty. c thi tr ch
yu qua mt dng chuyn ha mt hot tnh.
Tc dng ph c tnh:
Trn tiu ha: thng xy ra nn ma, km n, bun nn (20 %).
D ng da (2 - 4 %), rng tc.
Ketoconazol gy mt s ri lon v ni tit nh chng v to nam gii, bt lc n
ng, ri lon kinh nguyt ph n. l do cht ny c ch h enzym thuc
cytochrom P - 450, lm ngn chn s sinh tng hp steroid v thng thn ngi.
Tc ng ny ty thuc vo liu dng v gim dn khi ngng tr liu.
Vim gan: him xy ra nhng rt nng, c th gy t vong.
Do ketoconazol gy qui thai th th nghim v c bi tit vo sa, thuc ny b
chng ch nh ph n c thai v cho con b.
Tng tc thuc
Ketoconazol l cht c ch enzym ca microsom gan, do lm tng nng
cyclosporin, phenytoin trong huyt tng.
Ketoconazol cng lm tng nng terfenadin v astemizol trong mu, dn n s
gim dn truyn tim v c th gy t vong do cn xon nh. Phi hp vi cisapride
(Prepulsid) cng gy xon nh.
Rifampicin c tc ng cm ng enzym gan mnh hn tc ng c ch enzym ca
ketoconazol, do lm gim nng ketoconazol trong huyt tng.
Cc cht khng acid v c ch tit acid lm gim hp thu ketoconazol.
Lm tng hot tnh ca cc thuc khng vitamin K dng ung v cc Sulfamid h
ng huyt.

64

S dng tr liu
iu tr cc bnh nhim nm Candida v cc nm khc thuc ph tc dng. t hay
khng c hiu qu ngi b suy gim min dch v bnh vim mng no.
Liu lng ung: Ketoconazol (Nizoral) 200 - 600 mg/ ngy, chia 2 - 3 ln.
S dng ti ch dng kem 2 %, du gi.
2.4.2. Miconazol
Miconazol (Daktarin) c hp thu km qua ung ung v kh qua dch no ty.
Hin nay cht ny ch yu c s dng tr nhim nm ti ch v ng tim tnh
mch c tc dng ton thn cho kh nhiu tc dng ph nh d ng, c th gy sc
phn v, vim au ch tim, ri lon tiu ha, thn kinh . Ngoi ra, miconazol dng
bng ng tim chch cng lm tng hot tnh ca cc thuc khng vitamin K, cc
thuc Sulfamid h ng huyt v c th gy cn xon nh tim khi dng ng thi
vi terfenadin, astemizol hay cisapride.
2.4.3. Itraconazol, Fluconazol
y l cc dn xut triazol c s dng gn y iu tr cc bnh nhim nm ton
thn, nht l ngi b suy gim min dch nh bnh nhn AIDS.
V c ch tc dng, cc triazol ny c ch chn lc hn cytochrom P - 450 ca nm
nn c tnh v mt ni tit thp hn nhiu so vi ketoconazol.
Dc ng hc
Itraconazol v fluconazol c hp thu tt qua ng ung v phn b tt vo cc m
ca c th.
Fluconazol c u im hn itraconazol v s hp thu qua ng ung ca cht ny
khng b nh hng bi thc n hay acid d dy. Ngoi ra, kh nng thm qua dch
no ty ca fluconazol tt hn nhiu so vi itraconazol.
Fluconazol c thi ra trong nc tiu dng c hot tnh, cn itraconazol c
chuyn ha v phn hy gan.
Tc dng ph c tnh
Cc tc dng c th xy ra liu cao hn 200 mg/kg/ ngy: bun nn, nn ma, au
u, au bng, tiu chy, ban da. c tnh gan him xy ra.
Tng tc thuc
c tnh tng t ketoconazol. Tuy nhin, hai im khc bit i vi fluconazol l
cht ny t lm tng nng terfenadin trong mu nh ketoconazol, itraconazol v cc
thuc lm gim acid d dy khng nh hng r n nng fluconazol trong mu.

65

S dng tr liu
iu tr nhim nm ton thn (ni tng). Fluconazol c xem l thuc chn lc
iu tr bc u trong vim mng no do Cryptococcus ngi b AIDS cng nh
ngn nga s ti pht ca bnh.
Liu lng:

Itraconazol (Sporanox): 100 - 400 mg/ ngy dng theo ba n.

Fluconazol (Triflucan): 50 - 400 mg/ ngy.

Trng hp nhim Cryptococcus: 400 mg/ ngy trong 6 - 8 tun.

3. THUC KHNG NM TC NG TI CH
3.1. CC CHT NGUN GC SINH HC
3.1.1. Cc Polyen
* Nystatin (Mycostatine):
Nystatin c c lp t Streptomyces noursei (1950).
Nystatin c cu trc tng t v cng c ch tc ng vi amphotericin B nhng c
tnh cao hn v khng c dng cho tc ng tan thn. Cht ny khng c hp
thu qua da v ng tiu ha.
Nystatin c s dng iu tr ti ch di dng:

Vin ung, dch treo (Mycostatine) tr nm Candida ming, rut. Liu 3 - 6 triu UI/
ngy chia lm 3 - 4 ln.

Vin t m o: 1 vin 100000 UI/ ngy trong hai tun tr nm Candida m o

(Mycostatine; phi hp thuc khc: Polygynax, Tergynan).

Thuc m (Mycostatine): 100000 UI/g tr nm Candida da

* Amphotericin B (Fungizone): Xem phn thuc khng nm ton thn.

S dng dng kem, thuc m, nc ra cha 3 % amphotericin B.
3.1.2. Griseofulvin
Xem phn thuc khng nm ton thn.
3.2. CC CHT TNG HP
3.2.1. Cc dn xut Imidazol v triazol
Dn xut Imidazol

Miconazol (Daktarin); Ketoconazol (Ketoderm).

Econazol (Spectazole); Clotrimazol (Trimysten).

Tioconazol (Vagistat, Trozyd); Oxiconazol (Oxistat).

66

Isoconazol (Fazol).

Dn xut triazol:

Terconazol (Terazol) v butoconazol (Gynomyk).

Do th nghim in vitro v s nhy cm ca nm vi cc thuc trn khng gip d

on c cc p ng lm sng nn vic la chn mt trong cc dn xut azol c
da trn gi c v hiu lc ca thuc.
3.2.2. Ciclopiroxolamin
Ciclopiroxolamin (Mycoster) l cht khng nm thuc nhm pyridon, c hot tnh trn
cc nm men, nm da v c th thm qua cht sng.
3.2.3. Terbinafin
Terbinafin (Lamisil) thuc nhm allylamin, ch yu tc dng trn nm da, nm men,
h tr trong tr nm mng .
3.2.4. Cc cht khng nm khc thng dng trong cc bnh nm da

Tolnaftate (Sporilline): Kem v dung dch.

Cloprothiazol (Therops): phi hp vi acid salicylic

Haloprogin (Halotex): Kem v dung dch.

Acid benzoic v acid salicylic (6 % - 3 %)

CU HI N TP
1. Pht biu no khng ng i vi ketoconazol
A.

B gim hp thu qua ng ung khi dng chung vi thuc khng acid

B.

C th gy t vong khi dng chung vi terfenadin

C.

C tc ng gy cm ng men thuc microsom gan

D.

C th gy mt s ri lon v ni tit bnh nhn

E.

t hay khng c hiu lc ngi b suy gim min dch

67

19. Nhim nm Candida ng tiu ha c iu tr vi thuc no di y cho

tc dng ti ch bng ng ung
A.

Amphotericin B

B.

Griseofulvin.

C.

Nystatin

D.

A v C ng.

E.

B v C ng

20. Thuc khng nm c th lm gim hiu lc ca thuc nga thai dng ung:
A.

Flucytosin

B.

Griseofulvin

C.

Ketoconazol

D.

Itraconazol

E.

Amphotericin B

21. Thuc chon lc trong iu tr bc u vim no do Cryptococcus ngi b

AIDS
A.

Ketoconazol

B.

Nystatin

C.

Fluconazol

D.

Griseofulvin

E.

Amphotericin B

22. Cn cho bnh nhn dng paracetamol v diphenhydramin (hoc prednisolon) trc
khi iu tr bng thuc nao di y

68

A.

Fluconazol

B.

Amphotericin B

C.

Sparfloxacin

D.

Isoniazid

E.

Flucytosin