huong dan su dung khangs in h

B Y T

S: 708/Q-BYT

CNG HA X HI CH NGHA VIT NAM c lp - T do - Hnh phc

H Ni, ngy 02 thng 3 nm 2015

QUYT NH V vic ban hnh ti liu chuyn mn

Hng dn s dng khng sinh

B TRNG B Y T

Cn c Lut khm bnh, cha bnh nm 2009;

Cn c Ngh nh s 63/2012/N-CP ngy 31/8/2012 ca Chnh Ph quy nh chc nng, nhim v, quyn hn v c cu t chc ca B Y t;

Theo ngh ca Cc trng Cc Qun l Khm, cha bnh,

QUYT NH:

iu 1. Ban hnh km theo Quyt nh ny ti liu chuyn mn Hng dn s dng khng sinh.

iu 2. Ti liu Hng dn s dng khng sinh ban hnh km theo Quyt nh ny c p dng ti cc c s khm bnh, cha bnh.

Cn c vo ti liu ny v iu kin c th ca n v, Gim c c s khm bnh, cha bnh xy dng v ban hnh ti liu Hng dn s dng khng sinh ph hp thc hin ti n v.

iu 3. Quyt nh ny c hiu lc k t ngy k ban hnh.

iu 4. Cc ng, b: Chnh Vn phng B, Chnh Thanh tra B, Cc trng Cc Qun l Khm, cha bnh, Cc trng v V trng cc Cc, V thuc B Y t, Gim c cc bnh vin, vin c ging bnh trc thuc B Y t, Gim c S Y t cc tnh, thnh ph trc thuc trung ng, Th trng Y t cc B, Ngnh v Th trng cc n v c lin quan chu trch nhim thi hnh Quyt nh ny./.

Ni nhn: - Nh iu 4; - B trng B Y t ( b/c); - Cc Th trng BYT; - Bo him X hi Vit Nam ( phi hp); - Cng thng tin in t BYT; - Website Cc KCB; - Lu VT, KCB.

KT. B TRNG TH TRNG

( k)

Nguyn Th Xuyn

B Y t | BAN BIN SON 1

B Y T

HNG DN S DNG KHNG SINH (ban hnh km theo Quyt nh s 708/Q-BYT ngy 02/03/2015)

H NI - 2015


Ch bin

PGS.TS. Nguyn Th Xuyn

ng ch bin

PGS. TS. Lng Ngc Khu

GS. TS. Trn Qu

GS.TS. Hong Th Kim Huyn

BAN BIN SON

GS.TS Trn Qu

GS.TS Hong Th Kim Huyn

GS.TS Nguyn Ln Vit

GS.TS Ng Qu Chu

GS.TS L Quang Cng

PGS.TS Trn Hu Khang

PGS.TS Nh Hn

PGS.TS Bch Quc Khnh

PGS.TS Trn An

PGS.TS Nguyn Gia Bnh

PGS.TS inh Th Kim Dung

PGS.TS Trng Thanh Hng

PGS.TS Bi V Huy

PGS.TS Nguyn Th Ngc Lan

PGS.TS Th Liu

PGS.TS o Vn Long

PGS.TS on Mai Phng

PGS.TS Nguyn Hu Su

PGS.TS Phm Th Hng Thi

PGS.TS Nguyn Th Vinh


TS.BS Trn Th T Chu

TS.BS L Xun Cung

TS.BS Phm Ngc ng

TS.BS Nguyn Hi Anh

TS.BS V Vn Gip

TS.BS Chu Th Hnh

TS.BS Nguyn Thanh Hi

TS.BS V Trng Khanh

TS.BS Nguyn Vn Knh

TS.BS Phan Thu Phng

TS.BS Trn Qu Tng

TS.BS L Th Dim Tuyt

TS.BS L Th Kim Xun

TS.DS Nguyn Th Lin Hng

TS.DS Phm Th Thy Vn

TS.DS V Th Thu Hng

Ths.BSCKII V B Quyt

BSCKII Hunh Phan Phc Linh

Ths.DS Cao Hng Thi

Ths.DS Nguyn Hng Nga

Ths.BS Lu Vn i

Ths.BS Giang Thc Anh

Ths.BS Bi Hi Bnh

Ths.BS Nguyn ng Tun

Ths.BS L Th Ngc Lan

Ths V Quc t

Ths Nguyn Th Thanh Huyn

Ths on Th Phng Lan


Ths T Th Diu Ngn

Ths Nguyn Kim Th

BS Thm Trng Khnh Vn

T TH K V BIN TP:

Ths Nguyn c Tin

Ths Ng Th Bch H

Ths Trng L Vn Ngc

Ths Nguyn Th i Phong

Ths Nguyn Th Thy

B mn Dc lm sng Trng i hc Dc H Ni

B Y t | MC LC 5

MC LC

Ban bin son ................................................................................................ 2 Mc lc .......................................................................................................... 5 Danh mc bng .............................................................................................. 8 Danh mc hnh v ....................................................................................... 10 T vit tt ting Anh ................................................................................... 11 T vit tt ting Vit ................................................................................... 13 Li ni u .................................................................................................. 15

PHN I. I CNG V KHNG SINH V VI KHUN HC ............. 17

CHNG I. I CNG V KHNG SINH ................................................................................ 19 M u ......................................................................................................... 21 Cc nhm khng sinh v tc dng ............................................................... 22 C ch tc dng ca khng sinh v phi hp khng sinh ........................... 35 Khi nim Dc ng hc/Dc lc hc (PK/PD) v ng dng ............... 39 Cc nguyn tc s dng khng sinh ............................................................ 46

CHNG II. I CNG V VI KHUN HC ......................................................................... 56 i cng v vi khun hc ................................................................................................................ 58 Vai tr ca vi sinh lm sng vi s dng khng sinh hp l ...................... 63 S khng khng sinh ca vi khun ......................................................... 67

PHN II. IU TR CC BNH NHIM KHUN ................................... 74

CHNG I. NHIM KHUN H HP ............................................................................................ 76 Vim ph qun cp ngi ln .................................................................. 78 Gin ph qun .............................................................................................. 82 t cp bnh phi tc nghn mn tnh ........................................................ 87 Vim phi mc phi cng ng ............................................................... 93 S dng khng sinh iu tr vim phi cng ng tr em ....................... 99 Vim phi bnh vin ................................................................................. 110 Vim phi lin quan n th my ............................................................. 117 p xe phi ................................................................................................. 128 Trn m mng phi ................................................................................... 132

CHNG II. NHIM KHUN HUYT V SC NHIM KHUN ................................... 137 Nhim khun huyt v sc nhim khun .................................................. 139

CHNG III. NHIM KHUN TIM MCH ................................................................................ 149 Thp tim .................................................................................................... 151 Vim ni tm mc nhim khun ............................................................... 155

CHNG IV. NHIM KHUN DA V M MM ................................................................... 159 Nht ........................................................................................................... 161 Vim nang lng ......................................................................................... 164

Vim m bo ............................................................................................. 168

B Y t | MC LC 6

CHNG V. NHIM KHUN TIU HA.................................................................................... 171 Tiu chy do vi khun ............................................................................... 173 Dit Helicobacter pylori trong bnh l d dy t trng ............................ 178 Nhim khun ng mt ........................................................................... 181 p xe gan do vi khun ............................................................................... 185 Vim ty cp c nhim khun ................................................................... 189 Vim phc mc .......................................................................................... 192

CHNG VI. NHIM KHUN C XNG KHP ......................................................... 197 Vim khp nhim khun ........................................................................... 199 Vim xng ty nhim khun ................................................................... 203 Vim c, p xe c nhim khun ................................................................ 206 Nhim khun ht t phi ............................................................................. 210

CHNG VII. NHIM KHUN SN PH KHOA V CC BNH LY TRUYN QUA NG TNH DC. .................................................................................................................... 215

S dng khng sinh trong d phng sn khoa .......................................... 217 Nhim khun nng do sn khoa ................................................................ 219 Vim m o niu o do vi khun ........................................................ 222 Bnh giang mai .......................................................................................... 225 Bnh lu ..................................................................................................... 235 Bnh h cam .............................................................................................. 239

CHNG VIII. NHIM KHUN MT ........................................................................................... 243 Cc cu trc ca mt c lin quan n cc bnh l nhim khun ............. 245 S dng khng sinh trong nhn khoa ........................................................ 246 Vim kt mc cp ...................................................................................... 253 Vim kt mc do lu cu ........................................................................... 256 Vim gic mc do vi khun ....................................................................... 258 Bnh mt ht ............................................................................................. 260 Vim t chc hc mt ............................................................................... 263 Vim m ni nhn sau vt thng xuyn nhn cu .................................. 267 Vim b mi do vi khun ............................................................................ 271 Vim ti l ................................................................................................. 273

CHNG IX. VIM MNG NO .................................................................................................... 277 Vim mng no m ................................................................................... 279

CHNG X. NHIM KHUN TIT NIU ................................................................................... 285 Vim thn b thn cp ............................................................................... 287 Si thn tit niu nhim khun .................................................................. 293 Vim niu o cp khng do lu ............................................................... 299 Vim bng quang cp ................................................................................ 302

CHNG XI. S DNG KHNG SINH CHO NGI BNH SUY GIM MIN DCH .................................................................................................................................... 307

Suy gim min dch (gim bch cu ht trung tnh v sau ghp ty) ....... 309

B Y t | MC LC 7

PH LC 1. HNG DN X TR VIM PHI CNG NG TR EM ........................................................................................................................... 313

PH LC 2. LIU KHNG SINH TRONG D PHNG PHU THUT... 316 PH LC 3. LA CHN KHNG SINH D PHNG PHU THUT ...... 317 PH LC 4. HNG DN TIM/TRUYN MT S LOI KHNG SINH ........................................................................................................................... 322

B Y t | DANH MC BNG 8

DANH MC BNG

Bng I.1. Phn loi khng sinh theo cu trc ha hc ........................................ 22

Bng I.2. Phn nhm khng sinh Penicilin v ph khng khun ........................ 24

Bng I.3. Cc th h Cephalosporin v ph khng khun .................................. 25

Bng I.4. Khng sinh carbapenem v ph tc dng ............................................ 26

Bng I.5. Cc th h khng sinh nhm quinolon v ph tc dng ...................... 33

Bng I.6. Phn loi khng sinh lin quan n c tnh dc lc hc ................. 42

Bng I.7. Phn loi khng sinh theo ch s PK/PD ............................................. 43

Bng I.8. Sinh kh dng ca mt s khng sinh ng ung ............................. 51

Bng I.9. C quan bi xut chnh ca mt s khng sinh ................................... 52

Bng I.10. Nguyn tc MINDME trong s dng khng sinh ............................. 53

Bng II.1. La chn khng sinh trong iu tr vim ph qun cp ..................... 80

Bng II.2. T l mi mc VPC hng nm tr < 5 tui theo khu vc trn th

gii (WHO).......................................................................................................... 99

Bng II.3. 15 nc c s tr mc vim phi cao nht ....................................... 100

Bng II.4. 15 nc c s tr t vong do vim phi cao nht ............................ 100

Bng II.5. Tnh hnh khng khng sinh ca 3 vi khun thng gp gy vim phi

tr em .............................................................................................................. 105

Bng II.6. La chn khng sinh iu tr theo kinh nghim .............................. 112

Bng II.7. La chn khng sinh cho mt s chng vi khun a khng thuc .. 114

Bng II.8. Yu t nguy c v cc vi sinh vt c bit ....................................... 119

Bng II.9. Liu dng, ng dng c th ca mt s khng sinh .................... 124

Bng II.10. La chn khng sinh theo kinh nghim ......................................... 145

Bng II.11. Liu dng - cch dng ca mt s khng sinh ............................... 146

Bng II.12. Ngh ngi theo mc vim.......................................................... 152

Bng II.13. Thuc v cch s dng trong iu tr bnh thp tim ...................... 153

Bng II.14. Phn loi mc nng ca nhim khun ng mt .................... 182

Bng II.15. Cc la chn khng sinh trong nhim khun ng mt .............. 184

Bng II.16. Cc la chn khng sinh trong p xe gan do vi khun .................. 187

B Y t | DANH MC BNG 9

Bng II.17. im Balthazar nh gi mc nng trn CT ............................ 190

Bng II.18. Liu lng v cch dng khng sinh iu tr vim phc mc ....... 195

Bng II.19. Phc khng sinh kinh nghim khi cha c kt qu vi sinh ....... 281

Bng II.20. Liu khng sinh khuyn co trn ngi bnhngi bnh vim mng

no c chc nng gan thn bnh thng............................................................ 282

Bng II.21. Mt s chng vi khun thng gp ngi bnhngi bnh st

gim bch cu ht trung tnh ............................................................................. 311

B Y t | DANH MC HNH V 10

DANH MC HNH V

Hnh I-1. Lin quan gia mt vi khun (CFU) vi thi gian cc mc MIC

khc nhau (Th trn chng P. aeruginosa ATCC27853 vi tobramycin,

ciprofloxacin v ticarcilin cc nng t 1/4 MIC n 64 MIC) ................... 42

Hnh I-2. Cc ch s PK/PD ................................................................................ 43

Hnh I-3. S cu to t bo vi khun .............................................................. 59

Hnh I-4. Vi h bnh thng c th ngi ........................................................ 61

Hnh I-5. S tc ng (ring r/ phi hp) ca beta-lactamase (c ESBL), gim

tnh thm qua mng ngoi (porin), thay i PBPs v h thng bm y dn n

s khng beta-lactam trc khun Gram-m. ............................................... 68

Hnh II-1. Cc cu trc ca mt c lin quan n ............................................. 245

B Y t | T VIT TT TING ANH 11

T VIT TT TING ANH

A6AP Acid 6-aminopenicilanic

A7AC Acid 7-aminocephalosporanic

ADN Deoxyribonucleic acid

ADR Adverse drug reaction (Tc dng khng mong mun)

AFB Acid Fast Bacillus (Nhum hunh quang tm vi khun khng acid)

BK Bacilie de Koch (Vi khun lao)

CFU Colony forming unit (khun lc)

CK Creatine kinase

CLSI Clinical and Laboratory Standards Institute (Vin tiu chun thc v lm sng v xt nghim)

CPIS Clinical Pulmonary Infection Score (im nh gi nhim khun phi trn lm sng)

CRP C-reactive protein (Protein phn ng C)

CT Computed tomography (Chp ct lp vi tnh)

ESBL Extended spectrum beta-lactamase (Beta-lactamase ph rng)

Hib Heamophilus influenzae type b (Haemophilus influenzae

nhm B)

HIV Human immunodeficiency virus

ICU Intensive care unit

INR International normalized ratio (T s bnh thng ha quc t)

KPC Klebsiella pneumoniae carbapenemase

MBC Minimum Bactericidal Concentration (nng ti thiu cn thit tiu dit vi khun)

MIC Minimum Inhibitory Concentration (Nng c ch ti thiu)

MDR Multi-drug resistant (a khng)

MRI Magnetic resonance imaging (Chp cng hng t)

B Y t | T VIT TT TING ANH 12

MRSA Methicillin resistant Staphylococcus aureus (T cu khng Methicilin)

MSSA Methicillin sensitive Staphylococcus aureus (T cu nhy cm vi Methicilin)

PAE Post-Antibiotic Effect (Tc dng hu khng sinh)

PALE Post-Antibiotic Leucocyt Enhancement Effect (Hiu qu bch cu sau khng sinh)

PaCO2 p lc ring phn ca carbonic trong mu ng mch

PaO2 p lc ring phn ca oxy trong mu ng mch

PCR Polymerase Chain Reaction (Phng php khuch i gen)

PD Pharmacodynamics (Dc lc hc)

PDR Pan-drug resistant (Ton khng)

PK Pharmacokinetics (Dc ng hc)

SpO2 Saturation of Peripheral Oxygen ( bo ha oxy trong mu)

TDM Therapeutic Drug Monitoring (Theo di nng thuc trong mu)

TMP-SMX Trimethoprim/Sulfamethoxazole

WHO World Health Organization (T chc Y t th gii)

B Y t | T VIT TT TING VIT 13

T VIT TT TING VIT

BV Bnh vin

CTM Cng thc mu

KC Khuyn co

KSDP Khng sinh d phng

NCPT Nc ct pha tim

NK Nhim khun

NKBV Nhim khun bnh vin

NKN Nhim khun nng

TB Tim bp

TCV T cu vng

TE Tr em

TM Tnh mch

TTT Thi tm thu

VK Vi khun

B Y t | LI NI U 14

B Y t | LI NI U 15

LI NI U

T khi pht hin ra khng sinh Penicilline n nay hng trm loi khng sinh v cc thuc tng t c pht minh v a vo s dng. S ra i ca khng sinh nh du mt k nguyn mi ca y hc v iu tr cc bnh nhim khun, cu sng hng triu triu ngi khi cc bnh nhim khun nguy him. Khng sinh cn c s dng rng ri trong trng trt, chn nui gia sc, gia cm v thy sn,

Tuy nhin cng do vic s dng rng ri, ko di v lm dng, cha hp l, an ton nn tnh trng khng khng sinh ca cc vi sinh vt (vi khun, vi rt, k sinh trng, nm, ) ngy mt gia tng. Mc khng thuc ngy cng trm trng lm nh hng n hiu qu iu tr, tin lng xu, nguy c t vong cao, thi gian iu tr ko di, chi ph iu tr tng cao, nh hng n sc khe ngi bnh v cng ng.

Cng vi cc nc trn th gii, Vit Nam hng ng tch cc li ku gi ca T chc Y t th gii Khng hnh ng hm nay, ngy mai khng c thuc cha v K hoch hnh ng quc gia v chng khng thuc giai on t nm 2013 n nm 2020 c ban hnh (Quyt nh s 2174/Q-BYT ngy 21/6/2013) nhm y mnh cc hot ng phng, chng khng thuc gp phn nng cao cht lng, hiu qu ca cng tc phng, chng dch bnh, khm bnh, cha bnh, bo v, chm sc v nng cao sc khe nhn dn.

Bin son ti liu Hng dn s dng khng sinh l mt trong nhiu nhim v ca K hoch hnh ng trn. Ban bin son c thnh lp theo Quyt nh s 4259/Q-BYT ngy 31/10/2012 gm cc chuyn gia u ngnh v y v dc. Ti liu cung cp nhng kin thc v k nng c bn, cp nht ng thi ph hp vi thc t ca Vit Nam v vic s dng khng sinh hp l, an ton ng dng trong cng tc khm, cha bnh, phng bnh, bo v chm sc v nng cao sc khe nhn dn, gp phn hn ch tnh trng khng khng sinh ang c nguy c gia tng hin nay.

Ti liu gm c 11 Chng v 55 bi, bao gm i cng v khng sinh v vi khun, s dng khng sinh trong cc bnh nhim khun thng gp (nhim khun h hp, tim mch, tiu ha, thn - tit niu,).

Ti liu c bin son cng phu, cht lng, cp nht v thc t Vit Nam, tuy nhin cng cn nhng thiu st. Rt mong cc gio s, cc chuyn gia v cc ng nghip, bn c gp kin b sung ti liu c hon chnh hn.

Chng ti trn trng cm n s ch o st sao ca PGS. TS. Nguyn Th Kim Tin - B trng B Y t, cc Gio s, Ph Gio s, Tin s, Thc s, Bc s, Dc s, cc thnh vin Ban bin son, cc chuyn gia u ngnh ca cc chuyn khoa rt c gng, dnh nhiu thi gian qu bu bin son, sa cha, thm nh cun sch ny v trn trng cm n s h tr ca AstraZeneca cho vic t chc v in n hon thin hng dn ny. y l ln n bn u tin ca cun sch, chc chn cn nhiu thiu st, chng ti rt mong nhn c s ng gp t Qu c gi v ng nghip cun sch ngy mt hon thin.

THAY MT BAN BIN SON

GS.TS. Trn Qu

B Y t | 16

B Y t | 17

PHN I. I CNG V KHNG SINH V VI KHUN HC

B Y t |

18

B Y t |

19

Chng I. i cng v khng sinh

B Y t |

20

B Y t | M U 21

M U

Khng sinh l mt nhm thuc c bit v vic s dng chng khng ch nh hng n ngi bnh m cn nh hng n cng ng. Vi nhng nc ang pht trin nh Vit Nam, y l mt nhm thuc quan trng v bnh l nhim khun nm trong s nhng bnh ng hng u c v t l mc bnh v t l t vong.

S lan trn cc chng vi khun khng khng sinh l vn cp bch nht hin nay. S xut hin cc chng vi khun khng nh hng n hiu qu iu tr v sc khe ngi bnh. Vic hn ch s pht sinh ca vi khun khng khng sinh l nhim v khng ch ca ngnh Y t m ca c cng ng nhm bo v nhm thuc ny.

Khng sinh c nh ngha:

Khng sinh (antibiotics) l nhng cht khng khun (antibacterial substances) c to ra bi cc chng vi sinh vt (vi khun, nm, Actinomycetes), c tc dng c ch s pht trin ca cc vi sinh vt khc.

Hin nay t khng sinh c m rng n c nhng cht khng khun c ngun gc tng hp nh cc sulfonamid v quinolon.

bo m s dng thuc hp l, cn nm vng nhng kin thc lin quan n khng sinh, vi khun gy bnh v ngi bnh.

Trong ti liu ny, cc thuc khng sinh c cp n bao gm tt c cc cht c tc dng trn vi khun gy bnh. Nhng cht c tc dng n vi rt v nm gy bnh s c cp n ti liu tip theo.

B Y t | CC NHM KHNG SINH V TC DNG 22

CC NHM KHNG SINH V TC DNG

Cc nhm khng sinh c sp xp theo cu trc ho hc. Theo cch phn loi ny, khng sinh c chia thnh cc nhm nh sau (Bng I.1):

Bng I.1. Phn loi khng sinh theo cu trc ha hc

TT Tn nhm Phn nhm

1 Beta-lactam Cc penicilin

Cc cephalosporin

Cc beta-lactam khc

Carbapenem

Monobactam

Cc cht c ch beta-lactamase

2 Aminoglycosid

3 Macrolid

4 Lincosamid

5 Phenicol

6 Tetracyclin Th h 1

Th h 2

7 Peptid Glycopeptid

Polypetid

Lipopeptid

8 Quinolon Th h 1

Cc fluoroquinolon: Th h 2, 3, 4

9 Cc nhm khng sinh khc

Sulfonamid

Oxazolidinon

5-nitroimidazol

1. KHNG SINH NHM BETA-LACTAM

Nhm beta-lactam l mt h khng sinh rt ln, bao gm cc khng sinh c cu trc ha hc cha vng beta-lactam. Khi vng ny lin kt vi mt cu trc vng khc s hnh thnh cc phn nhm ln tip theo: nhm penicilin, nhm cephalosporin v cc beta-lactam khc.

1.1. Phn nhm penicilin

- Cc thuc khng sinh nhm penicilin u l dn xut ca acid 6-aminopenicilanic (vit tt l A6AP). Trong cc khng sinh nhm penicilin, ch


c penicilin G l khng sinh t nhin, c chit xut t mi trng nui cy Penicilium. Cc khng sinh cn li u l cc cht bn tng hp.

- S thay i nhm th trong cu trc ca penicilin bn tng hp dn n s thay i tnh bn vng vi cc enzym penicilinase v beta-lactamase; thay i ph khng khun cng nh hot tnh khng sinh trn cc chng vi khun gy bnh.

- Da vo ph khng khun, c th tip tc phn loi cc khng sinh nhm Penicilin thnh cc phn nhm vi ph khng khun tng ng nh sau:

+ Cc penicilin ph khng khun hp

+ Cc penicilin ph khng khun hp ng thi c tc dng trn t cu

+ Cc penicilin ph khng khun trung bnh

+ Cc penicilin ph khng khun rng ng thi c tc dng trn trc khun m xanh.

- i din ca mi phn nhm v ph khng khun tng ng c trnh by trong Bng I.2.

1.2. Phn nhm cephalosporin

- Cu trc ha hc ca cc khng sinh nhm cephalosporin u l dn xut ca acid 7-aminocephalosporanic (vit tt l A7AC). Cc cephalosporin khc nhau c hnh thnh bng phng php bn tng hp. S thay i cc nhm th s dn n thay i c tnh v tc dng sinh hc ca thuc.

- Cc cephalosporin bn tng hp tip tc c chia thnh 4 th h. S phn chia ny khng cn cn c trn cu trc ha hc m ch yu da vo ph khng khun ca khng sinh. Xp theo th t t th h 1 n th h 4, hot tnh trn vi khun Gram-dng gim dn v hot tnh trn vi khun Gram-m tng dn. Ph khng khun ca mt s cephalosporin trong tng th h c trnh by trong Bng I.3. Lu thm l tt c cc cephalosporin hu nh khng c tc dng trn enterococci, Listeria monocytogenes, Legionella spp., S. aureus khng methicilin, Xanthomonas maltophilia, v Acinetobacter spp.


Bng I.2. Phn nhm khng sinh Penicilin v ph khng khun

Phn nhm Tn thuc Ph khng khun

Cc penicilin ph khng khun hp

Penicilin G

Penicilin V

Cu khun Gram-dng (tr cu khun tit penicilinase, do khng c tc dng trn phn ln cc chng S. aureus).

Cc penicilin ph khng khun hp ng thi c tc dng trn t cu

Methicilin

Oxacilin

Cloxacilin

Dicloxacilin

Nafcilin

Hot tnh khng khun km hn trn cc vi khun nhy cm vi penicilin G, nhng do c kh nng khng penicilinase nn c tc dng trn cc chng tit penicilinase nh S. aureus v S. epidermidis cha khng methicilin.

Cc penicilin ph khng khun trung bnh

Ampicilin

Amoxicilin

Ph khng khun m rng hn so vi penicilin G trn cc vi khun Gram-m nh Haemophilus influenzae, E. coli, v Proteus mirabilis. Cc

thuc ny khng bn vng vi enzym beta-lactamase nn thng c phi hp vi cc cht c ch beta-lactamase nh acid clavulanic hay sulbactam.

Cc penicilin ph khng khun rng ng thi c tc dng trn trc khun m xanh

Carbenicilin

Ticarcilin

Ph khng khun m rng hn trn cc chng vi khun Gram-m nh Pseudomonas, Enterobacter, Proteus spp. C hot tnh mnh hn so vi ampicilin trn cu khun Gram-dng v Listeria monocytogenes, km hn piperacilin trn Pseudomonas.

Mezlocilin

Piperacilin

C tc dng mnh trn cc chng Pseudomonas, Klebsiella, v mt s chng vi khun Gram-m khc. Piperacilin vn gi c hot tnh tng t ampicilin trn t cu Gram-dng v Listeria monocytogenes.


Bng I.3. Cc th h Cephalosporin v ph khng khun

Th h Tn thuc Ph khng khun

Cephalosporin th h 1

Cefazolin

Cephalexin

Cefadroxil

C hot tnh mnh trn cc chng vi khun Gram-dng nhng hot tnh tng i yu trn cc chng vi khun Gram-m. Phn ln cu khun Gram-dng nhy cm vi cephalosporin th h 1 (tr enterococci, S. epidermidis v S. aureus khng

methicilin). Hu ht cc vi khun k kh trong khoang ming nhy cm, nhng vi B. fragilis thuc khng c hiu qu. Hot tnh tt trn cc chng Moraxella catarrhalis, E. coli, K. pneumoniae, v P. mirabilis.


Cefoxitin

Cefaclor

Cefprozil

Cefuroxim

Cefotetan

Ceforanid

Cc cephalosporin th h 2 c hot tnh mnh hn trn vi khun Gram-m so vi th h 1 (nhng yu hn nhiu so vi th h 3). Mt s thuc nh cefoxitin, cefotetan cng c hot tnh trn B. fragilis


Cefotaxim

Cefpodoxim

Ceftibuten

Cefdinir

Cefditoren

Ceftizoxim

Ceftriaxon

Cefoperazon

Ceftazidim

Cc cephalosporin th h 3 ni chung c hot tnh km hn th h 1 trn cu khun Gram-dng, nhng c hot tnh mnh trn vi khun h Enterobacteriaceae (mc d hin nay cc chng vi khun thuc h ny ang gia tng khng thuc mnh m do kh nng tit beta-lactamase). Mt s cc thuc nh ceftazidim v cefoperazon c hot tnh trn P. aeruginosa nhng li km cc thuc khc trong cng th h 3 trn cc cu khun Gram-dng.

Cephalosporin th h 4 Cefepim

Cephalosporin th h 4 c ph tc dng rng hn so vi th h 3 v bn vng hn vi cc beta-lactamase (nhng khng bn vi Klebsiella pneumoniae carbapenemase

(KPC) nhm A). Thuc c hot tnh trn c cc chng Gram-dng, Gram-m (bao gm Enterobacteriaceae v Pseudomonas)


1.3. Cc beta-lactam khc

a) Nhm carbapenem

Nghin cu bin i cu trc ha hc ca penicilin v cephalosporin to thnh mt nhm khng sinh beta-lactam mi, c ph khng khun rng, c bit c hot tnh rt mnh trn vi khun Gram-m l khng sinh nhm carbapenem. Tn thuc v ph tc dng ca mt s khng sinh trong nhm ny c trnh by trong Bng I.4.

Bng I.4. Khng sinh carbapenem v ph tc dng

Tn khng sinh Ph tc dng

Imipenem

Thuc c ph tc dng rt rng trn c vi khun hiu kh v k kh. Cc chng vi khun nhy cm bao gm streptococci (k c ph cu khng penicilin), enterococci (nhng khng bao gm E. faecium v cc chng khng penicilin khng do sinh enzym beta-lactamase), Listeria. Mt vi chng t cu khng methicilin c th nhy cm vi thuc, nhng phn ln cc chng ny khng. Hot tnh rt mnh trn Enterobacteriaceae (tr cc chng tit carbapenemase KPC). Tc dng c trn phn ln cc chng Pseudomonas v Acinetobacter. Tc ng trn nhiu chng k kh, bao gm c B. fragilis. Khng bn vng i vi men DHP-1 ti thn nn cn phi hp cilastatin.

Meropenem Ph tc dng tng t imipenem, c tc dng trn mt s chng Gram (-) nh P. aeruginosa, k c khng imipenem.

Doripenem

Ph tc dng tng t imipenem v meropenem.

Tc dng trn vi khun Gram-dng tng t imipenem, tt hn so vi meropenem v ertapenem.

Ertapenem Ph tc dng tng t cc carbapenem nhng tc dng trn cc chng Pseudomonas v Acinetobacter yu hn so vi cc thuc cng nhm.

b) Nhm monobactam

- Khng sinh monobatam l khng sinh m cng thc phn t c cha beta-lactam n vng. Cht in hnh ca nhm ny l aztreonam.

- Ph khng khun ca aztreonam kh khc bit vi cc khng sinh h beta-lactam v c v gn hn vi ph ca khng sinh nhm aminoglycosid. Thuc ch c tc dng trn vi khun Gram-m, khng c tc dng trn vi khun Gram-dng v vi khun k kh. Tuy nhin, hot tnh rt mnh trn Enterobacteriaceae v c tc dng i vi P. aeruginosa.

c) Cc cht c ch beta-lactamase

Cc cht ny cng c cu trc beta-lactam, nhng khng c hot tnh khng khun, m ch c vai tr c ch enzym beta-lactamase do vi khun tit ra. Cc cht hin hay c s dng trn lm sng l acid clavulanic, sulbactam v tazobactam.


1.4. Tc dng khng mong mun (ADR) ca cc khng sinh nhm beta-lactam:

- D ng vi cc biu hin ngoi da nh m ay, ban , mn nga, ph Quincke gp vi t l cao. Trong cc loi d ng, sc phn v l ADR nghim trng nht c th dn n t vong.

- Tai bin thn kinh vi biu hin kch thch, kh ng. Bnh no cp l ADR thn kinh trm trng (ri lon tm thn, ni sng, co git, hn m), tuy nhin tai bin ny thng ch gp liu rt cao hoc ngi bnhngi bnh suy thn do tr thuc gy qu liu.

- Cc ADR khc c th gp l gy chy mu do tc dng chng kt tp tiu cu ca mt s cephalosporin; ri lon tiu ho do lon khun rut vi loi ph rng.

2. KHNG SINH NHM AMINOGLYCOSID

Cc aminosid c th l sn phm t nhin phn lp t mi trng nui cy cc chng vi sinh, cng c th l cc khng sinh bn tng hp. Cc khng sinh thuc nhm ny bao gm kanamycin, gentamicin, neltimicin, tobramycin, amikacin.

2.1. Ph khng khun

Cc khng sinh nhm aminoglycosid c ph khng khun ch yu tp trung trn trc khun Gram-m, tuy nhin ph khng khun ca cc thuc trong nhm khng hon ton ging nhau. Kanamycin cng nh streptomycin c ph hp nht trong s cc thuc nhm ny, chng khng c tc dng trn Serratia hoc P. aeruginosa. Tobramycin v gentamicin c hot tnh tng t nhau trn cc trc khun Gram-m, nhng tobramycin c tc dng mnh hn trn P. aeruginosa v Proteus spp., trong khi gentamicin mnh hn trn Serratia. Amikacin v trong mt s trng hp l neltimicin, vn gi c hot tnh trn cc chng khng gentamicin v cu trc ca cc thuc ny khng phi l c cht ca nhiu enzym bt hot aminoglycosid.

2.2. Tc dng khng mong mun (ADR):

- Gim thnh lc v suy thn l 2 loi ADR thng gp nht. C 2 loi ADR ny s tr nn trm trng (ic khng hi phc, hoi t ng thn hoc vim thn k) khi s dng ngi bnhngi bnh suy thn, ngi cao tui (chc nng thn gim) hoc dng ng thi vi thuc c cng c tnh (vancomycin, furosemid).

- Nhc c cng l ADR c th gp khi s dng aminoglycosid do tc dng c ch dn truyn thn kinh c. ADR ny t gp nhng t l tng ln khi s dng phi hp vi thuc mm c cura (do cn lu ngng khng sinh trc ngy ngi bnhngi bnh cn phu thut). Tc dng lit c h hp c th gp nu tim tnh mch trc tip do to nng cao t ngt trong mu; v


vy khng sinh ny ch c truyn tnh mch (truyn qung ngn) hoc tim bp.

- Nhng ADR thng thng nh gy d ng da (ban da, mn nga) hoc sc qu mn cng gp vi nhm khng sinh ny.

3. KHNG SINH NHM MACROLID

3.1. Phn loi

Cc macrolid c th l sn phm t nhin phn lp t mi trng nui cy cc chng vi sinh, cng c th l cc khng sinh bn tng hp. Ty theo cu trc ha hc, c th chia khng sinh nhm macrolid thnh 3 phn nhm:

- Cu trc 14 nguyn t carbon: erythromycin, oleandomycin, roxithromycin, clarithromycin, dirithromycin.

- Cu trc 15 nguyn t carbon: azithromycin.

- Cu trc 16 nguyn t carbon: spiramycin, josamycin.

3.2. Ph khng khun

- Macrolid c ph khng khun hp, ch yu tp trung vo mt s chng vi khun Gram-dng v mt s vi khun khng in hnh.

- Macrolid c hot tnh trn cu khun Gram-dng (lin cu, t cu), trc khun Gram-dng (Clostridium perfringens, Corynebacterium diphtheriae, Listeria monocytogenes). Thuc khng c tc dng trn phn ln cc chng trc khun Gram-m ng rut v ch c tc dng yu trn mt s chng vi khun Gram-m khc nh H. influenzae v N. meningitidis, tuy nhin li c tc dng kh tt trn cc chng N. gonorrhoeae. Khng sinh nhm macrolid tc dng tt trn cc vi khun ni bo nh Campylobacter jejuni, M. pneumoniae, Legionella pneumophila, C. trachomatis, Mycobacteria (bao

gm M. scrofulaceum, M. kansasii, M. avium-intracellulare nhng khng tc dng trn M. fortuitum).


- ADR thng gp nht l cc tc dng trn ng tiu ho: gy bun nn, nn, au bng, a chy (gp khi dng ng ung), vim tnh mch huyt khi (khi tim tnh mch). Thuc b chuyn ho mnh khi qua gan nn c th gy vim gan hoc mt. C th gy ic, lon nhp tim nhng vi t l thp.

- Nhng ADR thng thng nh gy d ng da (ban da, mn nga) hoc sc qu mn cng gp vi nhm khng sinh ny.

4. KHNG SINH NHM LINCOSAMID

Nhm khng sinh ny bao gm hai thuc l lincomycin v clindamycin, trong lincomycin l khng sinh t nhin, clindamycin l khng sinh bn tng hp t lincomycin.

4.1. Ph khng khun


- Khng sinh nhm lincosamid c ph khng khun tng t nh khng sinh nhm macrolid trn pneumococci, S. pyogenes, v viridans streptococci.

Thuc c tc dng trn S. aureus, nhng khng c hiu qu trn S. aureus khng methicilin. Thuc cng khng c tc dng trn trc khun Gram-m hiu kh.

- Khc vi macrolid, khng sinh lincosamid c tc dng tt trn mt s chng vi khun k kh, c bit l B. fragilis. Thuc c tc dng tng i tt trn C. perfringens, nhng c tc dng khc nhau trn cc chng Clostridium spp. khc.

- Cng khc vi macrolid, khng sinh nhm ny ch tc dng yu hoc khng c tc dng trn cc chng vi khun khng in hnh nh M. pneumoniae hay Chlamydia spp.


Tc dng khng mong mun thng gp nht l gy a chy, thm ch trm trng do bng pht Clostridium difficile, gy vim i trng gi mc c th t vong. Vim gan, gim bch cu a nhn trung tnh cng gp nhng him v c th hi phc.

5. KHNG SINH NHM PHENICOL

Nhm khng sinh ny bao gm hai thuc l cloramphenicol v thiamphenicol, trong cloramphenicol l khng sinh t nhin, cn thiamphenicol l khng sinh tng hp.

5.1. Ph khng khun

- Khng sinh nhm phenicol c ph khng khun rng, bao gm cc cu khun Gram-dng, mt s vi khun Gram-m nh H. influenzae, N. meningitidis, N. gonorrhoeae, Enterobacteriaceae (Escherichia coli, Klebsiella

pneumoniae, Salmonella, Shigella). Thuc c tc dng trn cc chng k kh nh Clostridium spp., B. fragilis. Thuc cng c tc dng trn cc chng vi khun khng in hnh nh Mycoplasma, Chlamydia, Rickettsia.

- Tuy nhin, do a vo s dng rt lu nn hin nay phn ln cc chng vi khun gy bnh khng cc thuc nhm phenicol vi t l cao, thm vo nhm thuc ny li c c tnh nghim trng trn to mu dn n hin ti thuc khng cn c s dng ph bin trn lm sng.


Tc dng ph gy bt sn tu dn n thiu mu trm trng gp vi cloramphenicol. Hi chng xm (Grey-syndrome) gy tm ti, tru mch v c th t vong, thng gp tr s sinh, nht l tr non. Hin khng sinh ny t c s dng do nguy c gy bt sn tu c th gp mi mc liu; tuy him gp nhng rt nguy him, d gy t vong.

6. KHNG SINH NHM CYCLIN


Cc thuc nhm ny gm c cc khng sinh t nhin v khng sinh bn tng hp. Cc thuc thuc nhm bao gm: chlortetracyclin, oxytetracyclin, demeclocyclin, methacyclin, doxycyclin, minocyclin.

6.1. Ph khng khun

- Cc khng sinh nhm cyclin c ph khng khun rng trn c cc vi khun Gram-m v Gram-dng, c vi khun hiu kh v k kh. Thuc cng c tc dng trn cc chng vi khun gy bnh khng in hnh nh Rickettsia, Coxiella burnetii, Mycoplasma pneumoniae, Chlamydia spp., Legionella spp.,

Ureaplasma,Ngoi ra, thuc cng hiu qu trn mt s xon khun nh Borrelia recurrentis, Borrelia burgdorferi (gy bnh Lyme), Treponema pallidum (giang mai), Treponema pertenue.

- L khng sinh c a vo iu tr t rt lu, hin nay t l khng tetracyclin ca vi khun gy bnh cng rt cao. Mt s cyclin s dng sau nh doxycyclin hay minocyclin c th tc dng c trn mt s chng vi khun khng vi tetracyclin.

6.2. Tc dng khng mong mun (ADR)

ADR c trng ca nhm l gn mnh vo xng v rng, gy chm pht trin tr em, hng rng, bin mu rng; thng gp vi tr di 8 tui hoc do ngi m dng trong thi k mang thai. Tc dng ph trn ng tiu ho gy kch ng, lot thc qun (nu b ng thuc ti y), au bng, bun nn, nn, a chy hay gp khi dng ng ung. c tnh trn thn hoc trn gan, gy suy thn hoc vim gan, mt. Tng p lc ni s c th gp tr nh, c bit nu dng phi hp vi vitamin A liu cao. Mn cm vi nh sng cng l ADR phi lu tuy him gp.

7. KHNG SINH NHM PEPTID

Cc khng sinh thuc nhm ny c cu trc ha hc l cc peptid. Dng trong lm sng hin nay c cc phn nhm:

- Glycopeptid (vancomycin, teicoplanin)

- Polypetid (polymyxin, colistin)

- Lipopeptid (daptomycin)

7.1. Khng sinh Glycopeptid

- Hin nay c hai khng sinh glycopeptid ang c s dng trn lm sng l vancomycin v teicoplanin. y l hai khng sinh u c ngun gc t nhin, c cu trc ha hc gn tng t nhau. Hai khng sinh ny c ph tc dng cng tng t nhau, ch yu trn cc chng vi khun Gram-dng (S. aureus, S. epidermidis, Bacillus spp., Corynebacterium spp); phn ln cc chng Actinomyces v Clostridium nhy cm vi thuc. Thuc khng c tc dng trn trc khun Gram-m v Mycobacteria. Trn lm sng, hai thuc ny ch yu c s dng trong iu tr S. aureus khng methicilin.


- Tc dng khng mong mun (ADR)

+ Vancomycin: tc dng khng mong mun hay gp nht vi vancomycin l vim tnh mch v phn ng gi d ng. Vi ADR gy vim tc tnh mch, truyn thuc chm v pha long ng cch s gim bt ng k nguy c phn ng ny. Phn ng gi d ng do vancomycin c kh nng gy c trc tip trn t bo mast, dn n gii phng t histamin, dn n cc biu hin nh ban d di: hi chng c (red-neck) hay ngi (red-man), tt huyt p, au v co tht c. ADR khc cng cn lu vi vancomycin l c tnh trn tai v trn thn, thng lin quan vi tng qu mc nng thuc trong mu. Ngoi ra thuc c th gy ADR l biu hin ca qu mn nh phn ng phn v, st, rt run, chng mt

+ Teicoplanin: tc dng khng mong mun chnh ca thuc l ban da, thng gp hn khi dng vi liu cao. ADR khc bao gm phn ng qu mn, st, gim bch cu trung tnh Thuc cng c c tnh trn tai nhng him gp.

7.2. Khng sinh Polypeptid

- Cc khng sinh c s dng trn lm sng thuc nhm ny bao gm polymyxin B (hn hp ca polymyxin B1 v B2) v colistin (hay cn gi l polymyxin E). Cc khng sinh ny u c ngun gc t nhin, c cu trc phn t a peptid, vi trng lng phn t ln n khong 1000 dalton. Ph tc dng ca hai thuc ny tng t nhau, ch tp trung trn trc khun Gram-m, bao gm Enterobacter, E. coli, Klebsiella, Salmonella, Pasteurella, Bordetella, v Shigella. Thuc cng c tc dng trn phn ln cc chng P.aeruginosa, Acinetobacter.

- Cc thuc nhm ny c c tnh cao, c bit l c tnh trn thn, v vy hin nay polymyxin ch dng ngoi, cn colistin ch c ch nh hn ch trong mt s trng hp vi khun Gram-m a khng, khi khng dng c cc khng sinh khc an ton hn.


Cc thuc nhm polypeptid khng c hp thu nu dng ngoi trn da v nim mc nguyn vn, v vy khng gy ADR ton thn. Tuy nhin, thuc vn c th gy mt s ADR dng qu mn khi dng ti ch. Khi dng ng tim, thuc gy c ch dn truyn thn kinh c, vi cc biu hin nh yu c hoc nguy him hn l ngng th. Cc ADR khc trn thn kinh khc bao gm d cm, chng mt, ni lp. Cc thuc nhm ny u rt c vi thn, cn gim st cht ch, c gng trnh dng cng vi cc thuc c thn khc nh khng sinh aminoglycosid.

7.3. Khng sinh Lipopeptid

- Khng sinh nhm ny c s dng trn lm sng l daptomycin, y l khng sinh t nhin chit xut t mi trng nui cy Streptomyces roseosporus.


- Ph khng khun: thuc c tc dng trn vi khun Gram-dng hiu kh v k kh nh staphylococci, streptococci, Enterococcus, Corynebacterium spp., Peptostreptococcus, Propionibacteria, Clostridium perfringensc bit, thuc c tc dng trn cc chng vi khun khng vancomycin, tuy nhin MIC trong cc trng hp ny cao hn so vi trn cc chng nhy cm vi vancomycin.


ADR c bn ca thuc ny l gy tn thng trn h c xng. c bo co v cc trng hp tiu c vn, tuy him gp. Tng Creatin kinase (CK) c th xy ra, nhng nu tng CK n thun thng khng cn dng thuc, tr khi tng CK km theo cc biu hin khc ca bnh l c. Trong th nghim lm sng pha 1 v pha 2, ghi nhn mt vi trng hp c biu hin ca bnh l thn kinh c, tuy nhin khng gp ADR ny trong th nghim lm sng pha 3.

8. KHNG SINH NHM QUINOLON

8.1. Phn loi v ph khng khun

- Cc khng sinh nhm quinolon khng c ngun gc t nhin, ton b c sn xut bng tng hp ha hc.

- Cc khng sinh trong cng nhm quinolon nhng c ph tc dng khng hon ton ging nhau. Cn c vo ph khng khun, theo mt s ti liu, quinolon tip tc c phn loi thnh cc th h nh tm tt trong Bng I.5.

8.2. Tc dng khng mong mun (ADR)

ADR c trng ca nhm l vim gn, t gn Asin; T l gp tai bin tng nu s dng trn ngi bnhngi bnh suy gan v/hoc suy thn, ngi cao tui hoc dng cng corticosteroid. Bin dng sn tip hp gp trn ng vt non, do cng c th gp tr em tui pht trin nhng rt him. Tc dng ph trn thn kinh trung ng, gy nhc u, kch ng, co git, ri lon tm thn, hoang tng. Cc ADR ca nhm khng sinh ny tng t cc cyclin l tc dng trn ng tiu ho, gy bun nn, nn, au bng, a chy hoc gy suy gan, suy thn, mn cm vi nh sng.


Bng I.5. Cc th h khng sinh nhm quinolon v ph tc dng

Khng sinh quinolon Ph tc dng

Th h 1

Acid Nalidixic Tc dng mc trung bnh trn cc chng trc khun Gram-m h Enterobacteriaceae. Cinoxacin

Th h 2

Loi 1:

Lomefloxacin

Norfloxacin

Enoxacin

Cc khng sinh ny vn thuc nhm fluoroquinolon (cu trc phn t c flo), tuy nhin ph khng khun cng ch yu ch tp trung trn cc chng trc khun Gram-m h Enterobacteriaceae.

Loi 2:

Ofloxacin

Ciprofloxacin

Fluoroquinolon loi ny c ph khng khun m rng hn loi 1 trn cc vi khun gy bnh khng in hnh. Ciprofloxacin cn c tc dng trn P. aeruginosa. Khng c tc dng trn ph cu v trn cc vi khun Gram-dng.

Th h 3

Levofloxacin

Sparfloxacin

Gatifloxacin

Moxifloxacin

Cc fluoroquinolon th h 3 vn c ph khng khun trn Enterobacteriaceae, trn cc chng vi khun khng in hnh. Khc vi th h 2, khng sinh th h 3 c tc dng trn ph cu v mt s chng vi khun Gram-dng, v vy i khi cn c gi l cc quinolon h hp.

Th h 4

Trovafloxacin

Khng sinh ny c hot ph rng, tc dng trn Enterobacteriaceae, P. aeruginosa, vi khun khng in hnh, S. aureus nhy cm vi methicilin, streptococci, vi khun k kh.

9. CC NHM KHNG SINH KHC

9.1. Nhm Co-trimoxazol

- Co-trimoxazol l dng thuc phi hp gia sulfamethoxazol vi trimethoprim. Ph khng khun ca hai thnh phn ny tng t nhau v s phi hp ny mang li tnh hip ng trn tc ng c ch tng hp acid folic ca vi khun. Ph khng khun ca Co-trimoxazol kh rng trn nhiu vi khun Gram-dng v Gram-m, tuy nhin Pseudomonas aeruginosa, Bacteroides fragilis, v enterococci thng khng thuc. Thm vo , do a vo s dng kh lu nn hin nay Co-trimoxazol b khng vi t l rt cao.

- Tc dng khng mong mun (ADR):

ADR c trng ca cc dn cht sulfonamid l cc phn ng d ng nh my ay, nga, pht ban, hi chng Stevens-Johnson hoc Lyell vi cc ban phng nc ton thn, c bit l lot hc t nhin (ming, b phn sinh dc, hu mn) km theo cc triu chng ton thn trm trng nh tru tim mch, st


cao, thm ch t vong. c tnh trn gan thn: gy tng transaminase, vim gan, vng da, mt hoc suy thn cp (thiu niu, v niu). Trn mu gy thiu mu do tan mu gp nhiu ngi thiu men G6PD.

9.2. Nhm oxazolidinon

- y l nhm khng sinh tng hp ha hc, vi i din l linezolid. Thuc c tc dng trn vi khun Gram-dng nh staphylococci, streptococci, enterococci, cu khun Gram-dng k kh, Corynebacterium spp., Listeria monocytogenes. Thuc hu nh khng c tc dng trn vi khun Gram-m c hiu kh v k kh. Trn lm sng, linezolid thng c ch nh trong cc trng hp vi khun Gram-dng khng cc thuc khng sinh khc nh S. pneumoniae khng penicilin, cc chng staphylococci khng methicilin trung gian v khng vancomycin, enterococci khng vancomycin.


Thuc c dung np tt, c th gp mt s tc dng khng mong mun nh ri lon tiu ha, au u, pht banng lu nht l tc dng c ch ty xng, vi cc biu hin thiu mu, gim bch cu, gim tiu cuTrong , xut huyt gim tiu cu hoc s lng tiu cu gim xung mc rt thp c th gp vi t l ti 2,4% trn cc ngi bnhngi bnh s dng linezolid, thng lin quan vi di t iu tr. Cn gim st cht ch tc dng khng mong mun ny.

9.3. Khng sinh nhm 5-nitro-imidazol

- Nh tn gi ca nhm thuc, cc thuc nhm ny l dn xut ca 5-nitro imidazol, c ngun gc tng hp ha hc. Mt s thuc thng c s dng trong lm sng l metronidazol, tinidazol, ornidazol, secnidazol Cc thuc ny ch yu c ch nh trong iu tr n bo (Trichomonas, Chlamydia, Giardia) v hu ht cc vi khun k kh (Bacteroides, Clostridium)


Thuc c th gy mt s ri lon tiu ha nh nn, bun nn, v kim loi, chn nNc tiu c th b sm mu do cht chuyn ha c mu ca thuc. Thuc c th gy ADR trn thn kinh nh bnh thn kinh ngoi bin, co git, au u, mt phi hp nhng him gp v thng lin quan n dng liu cao. Do tc dng ging disulfiram, khng nn ung ru khi dng thuc.

B Y t | C CH TC DNG CA KHNG SINH V PHI HP KHNG SINH

35

C CH TC DNG CA KHNG SINH V PHI HP KHNG SINH

1. C CH TC DNG CA KHNG SINH

Sau khi vo t bo, khng sinh c a ti ch tc ng 4 thnh phn cu to c bn ca t bo (xem thm bi i cng v vi khun hc, phn Cu to t bo vi khun) v pht huy tc dng: km hm s sinh trng & pht trin hoc tiu dit vi khun, c bit c hiu qu cc vi khun ang sinh trng v pht trin mnh (giai on 2/ log phase pht trin theo cp s nhn), bng cch:

a) c ch sinh tng hp vch t bo vi khun: cc khng sinh nhm beta-lactam, fosfomycin v vancomycin ngn cn sinh tng hp lp peptidoglycan nn khng to c khung murein tc l vch khng c hnh thnh. T bo con sinh ra khng c vch, va khng sinh sn c va d b tiu dit hoc b li gii, c bit vi khun Gram-dng. Nh vy, nhng khng sinh ny c tc dng dit khun nhng ch vi nhng t bo ang pht trin (degenerative bactericide).

b) Gy ri lon chc nng mng bo tng: chc nng c bit quan trng ca mng bo tng l thm thu chn lc; khi b ri lon cc thnh phn (ion) bn trong t bo b thot ra ngoi v nc t bn ngoi o t vo trong, dn ti cht, v d polymyxin B, colistin. Vi c ch tc ng ny, polymyxin c tc dng dit khun tuyt i (absolute bactericide), tc l git c t bo ang nhn ln v c t bo trng thi ngh - khng nhn ln.

c) c ch sinh tng hp protein: tham gia sinh tng hp protein ngoi ribosom cn c cc ARN thng tin v cc ARN vn chuyn. im tc ng l ribosom 70S ca vi khun: ti tiu phn 30S v d nh aminoglycosid (ni ARN thng tin trt qua), tetracyclin (ni ARN vn chuyn mang acid amin ti) hoc ti tiu phn 50S (ni acid amin lin kt to polypeptid) nh erythromycin, cloramphenicol, clindamycin. Kt qu l cc phn t protein khng c hnh thnh hoc c tng hp nhng khng c hot tnh sinh hc lm ngng tr qu trnh sinh trng v pht trin.

d) c ch sinh tng hp acid nucleic: gm 3 cp :

- Ngn cn s sao chp ca ADN m to ADN con, v d do khng sinh gn vo enzym gyrase lm ADN khng m c vng xon, nh nhm quinolon.

- Ngn cn sinh tng hp ARN, v d do gn vo enzym ARN-polymerase nh rifampicin.

- c ch sinh tng hp cc cht chuyn ha cn thit cho t bo: qu trnh sinh tng hp acid folic coenzym cn cho qu trnh tng hp cc purin & pyrimidin (v mt s acid amin) b ngn cn bi sulfamid v trimethoprim.


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Nh vy, mi khng sinh ch tc ng ln mt v tr nht nh trong thnh phn cu to, nh hng n mt khu nht nh trong cc phn ng sinh hc khc nhau ca t bo vi khun, dn n ngng tr sinh trng v pht trin ca t bo.

Nu vi khun khng b li gii hoc khng b nm bt (thc bo) v tiu dit, th khi khng cn tc ng ca khng sinh (ngng thuc) vi khun s c th hi phc/ sng tr li (reversible). Ch cn 1 t bo sng st, vi tc sinh sn nhanh chng, sau vi gi s lng t bo vi khun khng th m c (v d E. coli nu 20 pht 1 la th sau 5 gi: t 1 t bo m - ban u pht trin thnh 2

15 t bo v sau 10 gi l 230 hn 1 t); s nguy him hn na nu t

bo sng st khng khng sinh.

2. PHI HP KHNG SINH

Trong thc t nng cao hiu qu iu tr, mt s trng hp cn thit chng ta phi phi hp khng sinh.

a) C s l thuyt cho phi hp khng sinh l nhm mc ch:

- Lm gim kh nng xut hin chng khng: vi nhng khng do t bin th phi hp khng sinh s lm gim xc sut xut hin mt t bin kp. V d: xc sut t bin khng streptomycin l 10-7 v t bin khng rifampicin l 10

-9, th xc sut t bin khng c 2 khng sinh ny l 10-16.

y chnh l l do phi phi hp khng sinh trong iu tr lao v phong; ngoi ra cn p dng cho mt s bnh phi iu tr ko di nh vim mng trong tim v vim ty xng.

- iu tr nhim khun do nhiu loi vi khun gy ra, v d do c vi khun hiu kh v k kh th phi hp beta-lactam vi metronidazol nh trng hp vim phc mc, p xe no, p xe phi, mt s nhim khun ph khoa Nh vy mi khng sinh dit mt loi vi khun, phi hp khng sinh s dit nhiu loi vi khun hn.

- Lm tng kh nng dit khun: v d sulfamethoxazol & trimethoprim (trong Co-trimoxazol) tc ng vo 2 im khc nhau trong qu trnh sinh tng hp acid folic hoc cp phi hp kinh in beta-lactam (penicilin hoc cephalosporin) vi aminoglycosid (gentamicin hoc tobramycin hay amikacin).

b) Kt qu ca phi hp khng sinh

Mi khng sinh u c t nhiu tc dng khng mong mun; khi phi hp th nhng tc dng ph ny cng s cng li hoc tng ln. Khng nn hy vng phi hp th h c liu lng tng thuc v c th dn n nguy c xut hin vi khun khng khng sinh.

Phi hp khng sinh c th dn n tc dng cng (addition) hoc hip ng (synergism) hoc i khng (antagonism) hay khng thay i (indifference) so vi 1 thuc n l.

- Tc dng i khng: 2 m tc dng khng bng 1 thuc.


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+ Phi hp cc khng sinh c cng mt ch tc ng s c tc dng i khng v chng y nhau ra khi ch, v d phi hp erythromycin vi clindamycin (hoc lincomycin) v cloramphenicol.

+ Dng tetracyclin cng penicilin c th dn n tc dng i khng, v penicilin c tc dng tt trn nhng t bo ang nhn ln, trong khi tetracyclin li c ch s pht trin ca nhng t bo ny.

- Tc dng hip ng (n gin ha c th ni: 1+1 ln hn 2):

+ Trimethoprim v sulfamethoxazol c ch 2 chng khc nhau trn cng mt con ng tng hp coenzym acid folic cn thit cho vi khun pht trin nn 2 thuc ny c tc dng hip ng v c phi hp thnh mt sn phm (Co-trimoxazol).

+ Cp phi hp kinh in: mt beta-lactam vi mt aminoglycosid cho kt qu hip ng do beta-lactam lm mt vch to iu kin cho aminoglycosid d dng xm nhp vo t bo v pht huy tc dng. V d phi hp piperacilin vi aminoglycosid iu tr nhim khun nng do trc khun m xanh; penicilin vi gentamicin nhm dit lin cu.

+ Phi hp penicilin vi mt cht c ch beta-lactamase gip cho penicilin khng b phn hy v pht huy tc dng; v d phi hp amoxicilin vi acid clavulanic hoc ampicilin vi sulbactam hay ticarcilin vi acid clavulanic. Acid clavulanic hoc sulbactam n c khng c tc dng ca mt khng sinh, nhng c i lc mnh vi beta-lactamase do plasmid ca t cu v nhiu trc khun ng rut sinh ra.

+ Phi hp 2 khng sinh cng c ch sinh tng hp vch vi khun, nu mi khng sinh tc ng vo mt protein gn penicilin (PBP) - enzym trong qu trnh tng hp vch th s c tc dng hip ng; v d phi hp ampicilin (gn PBP1) vi mecilinam (gn PBP2) hay ampicilin vi ticarcilin.

c) Ch dn chung cho phi hp khng sinh

- Phi hp khng sinh l cn thit cho mt s t trng hp nh iu tr lao, phong, vim mng trong tim, Brucellosis.

- Ngoi ra, c th phi hp khng sinh cho nhng trng hp: bnh nng m khng c chn on Vi sinh hoc khng ch c kt qu xt nghim; ngi suy gim sc khng; nhim khun do nhiu loi vi khun khc nhau.

- Khi phi hp, cn dng liu v nn la chn nhng khng sinh c tnh cht dc ng hc gn nhau hoc c tc dng hip ng. Tc dng khng khun in vivo (trong c th) thay i ty theo s lng v tui (non - ang sinh sn mnh hay gi) ca vi khun gy bnh cng nh cc thng s dc ng hc ca cc khng sinh c dng phi hp.

- Mt s v d: nhim khun nng do t cu c th dng cc phi hp khc nhau nh oxacilin (hoc flucloxacilin) vi acid fusidic hoc cephalosporin th h 1 vi aminoglycosid hoc aminoglycosid vi clindamycin. Khi nhim vi


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khun k kh th dng metronidazol phi hp cha vim phc mc hay cc nhim khun bng; nu nghi nhim vi khun k kh vng u v ng h hp th dng cng clindamycin (khng sinh ny c tc dng tt trn c vi khun Gram-dng v vi khun k kh).

- Quan st in vivo cho thy phn ln cc phi hp khng sinh c kt qu khng khc bit (indifferent) so vi dng mt khng sinh, trong khi cc tc dng khng mong mun do phi hp li thng gp hn; v vy cn thn trng v gim st tt ngi bnh khi k n khng sinh.

B Y t | KHI NIM DC NG HC/DC LC HC (PK/PD) V NG DNG

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KHI NIM DC NG HC/DC LC HC (PK/PD) V NG DNG

1. MT S KHI NIM LIN QUAN TI PK/PD CA KHNG SINH

Ch s lin kt c tnh dc ng hc (Pharmacokinetics) v dc lc hc (Pharmacodynamics), k hiu l PK/PD, c p dng nng cao tnh hiu qu v an ton khi s dng khng sinh. i vi cc khng sinh, cc nghin cu trc y thng ch tp trung vo c tnh dc lc hc ngha l kh nng c ch hoc tiu dit vi khun in vitro, t xc nh cc gi tr MIC/MBC - nng ti thiu c ch hoc dit vi khun, lm c s cho la chn cc mc liu. Cc gi tr MIC/MBC l cc ch s rt quan trng phn nh hot lc ca khng sinh i vi vi khun nhng cc tr s ny n thun t nghin cu in vitro, khng d on hot tnh y ca khng sinh trn lm sng. Hiu qu khng khun trn lm sng ph thuc nhiu vo din bin nng thuc trong c th ngi bnh tc l vo c tnh dc ng hc ca khng sinh. Cc ch s PK/PD ca khng sinh c thit lp trn c s nng thuc trong huyt tng (gi tr u vo ca dc ng hc) v nng c ch ti thiu (gi tr u vo ca dc lc hc), nh phn nh chnh xc hn hiu qu ca thuc in vivo, khc phc c hn ch trn.

Cc thng s xc nh hot tnh khng khun in vitro

a) MIC v MBC

- MIC (Minimum Inhibitory Concentration) l nng ti thiu ca khng sinh c tc dng c ch s tng trng ca vi khun mc c th quan st c; MBC (Minimum Bactericidal Concentration) l nng ti thiu cn thit tiu dit vi khun. y l cc thng s ch yu c s dng xc nh hot tnh khng khun in vitro i vi cc chng vi khun. Khi t l MBC/MIC > 4, khng sinh c tc dng km khun, cn khi t l ny bng 1, khng sinh c tc dng dit khun. Khng sinh km khun thng c s dng trong nhng trng hp nhim khun nh v trung bnh, trn c a ngi bnhngi bnh c sc khng. Cc nhm khng sinh c tc dng km khun l: macrolid, tetracyclin, phenicol, lincosamid. Khng sinh dit khun c dng cho cc nhim khun nng, trn nhng ngi bnhngi bnh yu, suy gim min dch. Cc nhm khng sinh c tc dng dit khun l: beta-lactam, aminoglycosid, fluoroquinolon, 5-nitro-imidazol, co-trimoxazol.

- MIC v MBC c xc nh ngoi c th (in vitro) nn cc iu kin tc ng ln vi khun c nhiu khc bit vi iu kin nhim khun trn lm sng, v d:

+ iu kin nui cy vi khun in vitro thng l hiu kh, vi mi trng lng c nng protein thp v pH 7,2 trong khi iu kin ti v tr nhim khun trong c th li a phn l mi trng k kh, c pH acid v ti y thuc c th dng lin kt vi protein ca t chc.


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+ Thi gian xc nh MIC v MBC l c nh k t khi m (thng l t 18-24 gi) v nng khng sinh cng khng i trong sut qu trnh nui cy trong khi nng ny bin i lin tc trong c th.

+ Mt vi khun a vo nui cy thng c nh mc 105 CFU/ml, v thng khng ging vi mt vi khun m nhim khun (thng t 108-10

10 CFU/g m hoc m) v vic nui cy in vitro cng to ra s tng trng vi

khun theo hm m, khc vi iu kin nhim khun trn lm sng, ch yu l vi khun khng tng sinh v thng phi hp vi tc dng hu khng sinh (post-antibiotic effect = PAE) ngha l kh nng c ch s pht trin ca vi khun k c khi khng cn khng sinh ti nhim khun.

Nh vy MIC v MBC xc nh in vitro n thun khng d on y c hot tnh ca khng sinh trn lm sng, ni m hot tnh khng khun ph thuc vo din bin nng thuc theo thi gian.

b) Tc dng hu khng sinh - PAE (Post-Antibiotic Effect):

- Tc dng hu khng sinh l mt thng s dc lc hc ca khng sinh. n v ca PAE c tnh theo n v thi gian (gi hoc pht). PAE c th c xc nh trong m hnh in vitro hoc in vivo. PAE in vitro l thut ng m t tc dng c ch s tng sinh vi khun sau khi vi khun tip xc vi khng sinh trong thi gian ngn. PAE in vitro phn nh thi gian cn thit vi khun hi phc v s lng sau khi tip xc vi khng sinh v c chng minh bi cc nghin cu in vitro s dng m hnh ng hc tng trng ca vi khun sau khi loi b khng sinh. C ch ca PAE c th l: (1) vi khun b khng sinh tc ng nhng ch b thng tn cu trc t bo v sau c th hi phc li m khng b tiu dit; (2) khng sinh vn duy tr v tr gn hoc trong khoang bo tng v (3) vi khun cn thi gian tng hp enzym mi trc khi tng trng tr li.

- Nhc im ca nh gi PAE in vitro l gi tr ny c xc nh khi khng c c ch phng v ca vt ch, do c nhng phng php xc nh PAE in vivo trn m hnh nhim khun trn ng vt. Trn m hnh in vivo, PAE phn nh s khc bit v thi gian mt lng vi khun tng thm 10 ln nhm th (ng vt c iu tr) so vi thi gian tng ng ca nhm chng, tnh t lc nng thuc huyt tng hoc m nhim khun gim xung di MIC.

Trong phn ln cc trng hp, PAE in vivo ko di hn cc PAE in vitro do c tc dng ca cc nng di MIC hoc c s tham gia ca bch cu v nh vy PAE di hay ngn ph thuc vo c tnh ca khng sinh v loi vi khun. Mt s loi khng sinh c th lm tng kh nng thc bo ca cc i thc bo trong c th vt ch, lm cho vi khun d b tiu dit hn (cc macrolid, penem, fluoroquinolon), iu ny cng lm tng PAE. c tnh ny cn c gi l PALE (Post-Antibiotic Leucocyt Enhancement Effect). Chnh v vy, PAE in vitro thng ngn hn PAE in vivo. Thc t th tt c cc khng


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sinh u c PAE nhng nu thi gian ko di khng ng k trong iu kin in vitro v khng c li th v lin kt mnh vi protein huyt tng hoc khng c PALE th PAE coi nh khng ng k. Theo c tnh dc lc hc ny, khng sinh c chia lm 2 loi:

+ Loi khng c PAE hoc PAE rt ngn:

Tiu biu cho loi ny l cc khng sinh beta-lactam. Ngi ta cho rng s d beta-lactam khng c PAE v c ch tc dng dit khun lin quan n s bin dng v v v t bo vi khun, ch xy ra khi vi khun c tip xc vi khng sinh.

+ Loi c PAE trung bnh hoc ko di:

Tiu biu cho loi c PAE di l cc khng sinh nhm aminoglycosid, rifampicin, fluoroquinolon, glycopeptid, tetracyclin v imidazol. Mt s khng sinh khc cng c c tnh ny l cc macrolid, carbapenem, lincosamid nhng ngn hn. Vi aminoglycosid s d c PAE di l do c ch c ch tng hp protein ca vi khun ko di to kh nng ngn cn ko di s pht trin tr li ca vi khun sau khi khng cn tip xc vi khng sinh na. Vi mt s khng sinh khc th PAE c c l nh c PALE hoc nh kh nng gn mnh vi protein ti t chc hoc do phn b mnh t bo vi khun.

c) c tnh dit khun ca khng sinh

- y l c tnh c lin quan n nng thuc trong mu, theo khng sinh c hai kiu tc dng chnh:

+ Kiu dit khun ph thuc nng (Concentration-dependent bactericidal activity):

Vi loi ny, tc v mc dit khun ph thuc vo ln ca nng khng sinh trong mu. Aminoglycosid, fluoroquinolon, daptomycin, ketolid, metronidazol, amphotericin B c kiu dit khun ny.

+ Kiu dit khun ph thuc thi gian: (Time-dependent bactericidal activity):

Vi loi ny, tc v mc dit khun ph thuc ch yu vo thi gian vi khun tip xc vi khng sinh, t ph thuc vo ln ca nng thuc trong mu. Kh nng dit khun t bo ha khi nng ln hn MIC khong 4 ln; khi tng hn na nng , tc v mc dit khun tng khng ng k. Nhm beta-lactam, macrolid, clindamycin, glycopeptid, tetracyclin, linezolid c kiu dit khun thuc nhm ny.


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Bng I.6. Phn loi khng sinh lin quan n c tnh dc lc hc

Khng c PAE hoc PAE ngn C PAE trung bnh hoc ko di

Cc Penicilin

Cc Cephalosporin

Monobactam (Aztreonam)

Aminosid

Imidazol

Fluoroquinolon

Glycopeptid

Macrolid

Tetracyclin

Carbapenem

Lincosamid

- Cc kiu dit khun khc nhau c gii thch nh Hnh I-1.

Hnh I-1. Lin quan gia mt vi khun (CFU) vi thi gian cc mc MIC khc nhau (Th trn chng P. aeruginosa ATCC27853 vi tobramycin, ciprofloxacin v

ticarcilin cc nng t 1/4 MIC n 64 MIC)

Hnh I-1biu din tc dit khun theo thi gian ca 3 khng sinh tobramycin, ciprofloxacin v ticarcilin i din cho 3 nhm khng sinh trn chng Pseudomonas aeruginosa ATCC 27853 vi cc nng tng dn. Nhn vo th c th thy: khi tng nng ca tobramycin v ciprofloxacin, tc v mc dit khun tng nhanh, th hin bng dc ng dit khun gim nhanh theo thi gian v do c gi l cc khng sinh c kiu dit khun ph thuc vo nng . Vi ticarcilin, ch c s thay i dc ca ng cong dit khun khi nng tng t 1 n 4 ln MIC cn khi tng nng cao hn (t trn 4 ln n 64 ln MIC) dc ng cong ch tng rt t; do cc khng sinh nhm ny c gi l cc khng sinh dit khun t ph thuc nng hay khng sinh ph thuc thi gian (ch lin quan n thi gian c nng trn MIC t 1-4 ln).

2. NG DNG CH S PK/PD TRONG S DNG KHNG SINH

a) Cc ch s PK/PD:

- Ch s PK/PD i vi khng sinh c thit lp trn c s nng thuc trong huyt tng (PK) v nng c ch ti thiu ca khng sinh i vi


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vi khun (PD). T cc nghin cu in vitro, c ba ch s PK/PD lin quan n tc dng ca khng sinh, l:

+ T>MIC: thi gian nng khng sinh duy tr mc cao hn MIC.

+ Cpeak/MIC: T l gia nng nh ca khng sinh v MIC.

+ AUC0-24/MIC: T l din tch di ng cong nng - thi gian trong 24 gi v MIC (Bng I.7).

Bng I.7. Phn loi khng sinh theo ch s PK/PD

Phn loi khng sinh Nhm i din Ch s PK/PD lin quan

n hiu qu

Khng sinh dit khun ph thuc thi gian v c tc dng hu khng sinh ngn hoc khng c

Beta-lactam T>MIC

Khng sinh dit khun ph thuc nng v c tc dng hu khng sinh trung bnh ti ko di

Aminoglycosid,

fluoroquinolon,

daptomycin,

metronidazol

Cpeak/MIC

v AUC0-24/MIC

Khng sinh dit khun ph thuc thi gian v c tc dng hu khng sinh trung bnh

Macrolid,

clindamycin,

glycopeptid,

tetracyclin

AUC0-24/MIC

Hnh I-2. Cc ch s PK/PD

- Trong nghin cu in vitro hoc in vivo trn ng vt, cc nhm khng sinh c nghin cu nhiu nht v ln ca cc ch s PK/PD l nhm khng sinh beta-lactam, fluoroquinolon v aminoglycosid.

+ Vi nhm khng sinh aminoglycosid:

Da trn cc nghin cu in vitro, hot tnh dit khun ti u ca nhm khng sinh ny t c khi Cpeak/MIC khong 8-10.

+ Nhm beta-lactam:


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T>MIC l ch s d bo hiu qu iu tr ca nhiu khng sinh nhm beta-lactam. Vi penicilin v cephalosporin, T>MIC cn chim 40-50% khong cch a thuc. Vi carbapenem, tc dng km khun v tc dng dit khun gn t ti a khi T>MIC ln lt l 20% v 40%.

+ Nhm fluoroquinolon: Ch s PK/PD lin quan vi hiu qu ca fluoroquinolon l AUC0-24/MIC. ln ca ch s ny to ra hiu qu km khun trn m hnh nhim khun trn ng vt l t 25-50, thay i i vi cc chng gy bnh thng gp. Trn lm sng, gi tr AUC0-24/MIC ca khng sinh nhm quinolon cho d bo hiu qu iu tr tt khc bit gia cc nghin cu v thng trn 100-125 i vi cc nhim khun Gram-m v trn 30 i vi vi khun Gram-dng. ng thi ch s Cpeak/MIC t 8-10 cng d bo hiu qu iu tr tt vi nhm khng sinh ny.

b) ng dng ch s PK/PD thit k ch liu iu tr:

- T nhng khuyn co trn, ngi ta xut cc mc liu dng cho c cc khng sinh c v mi, c bit c ch vi cc chng khng, khi cc mc liu thng thng khng c hiu qu. ti u ha iu tr, tng kh nng t ch s PK/PD khuyn co, trong mt s trng hp, phi thay i ch liu ca khng sinh v s thay i ny c p dng ch yu cho nhng trng hp sau:

+ Ngi bnhNgi bnh c thay i thng s dc ng hc ca khng sinh (ngi bnhngi bnh khoa iu tr tch cc, ngi bnhngi bnh bng nng, bo ph, tiu ng, ngi bnhngi bnh suy gan, suy thn, ngi gi, tr s sinh v tr nh...). y l nhng trng hp c thay i dc ng hc (PK) dn n thay i nng thuc trong mu. Lc ny vic hiu chnh liu ca thuc s c tnh ton da vo cc cng thc hiu chnh theo thng s dc ng hc ca c th ngi bnhngi bnh hoc da vo dc ng hc qun th v cn gim st iu tr thng qua theo di nng thuc trong mu (Therapeutic Drug Monitoring TDM).

+ Ngi bnhNgi bnh mc cc bnh l nhim khun nng do cc chng vi khun khng thuc: nhim khun huyt do trc khun m xanh, vim phi bnh vin do trc khun Gram-m, nhim khun trn ngi bnhngi bnh c dng c nhn to.... Nhng trng hp ny MIC tng cao nn mc liu dng thng thng khng p ng hiu qu iu tr, do cn tng liu. Vic tng liu nhm t ch s PK/PD khuyn co.

- Cho n nay, cc phng php ti u ha ch liu nhm gia tng hiu qu iu tr ca khng sinh, gia tng kh nng t c ch s PK/PD trong iu kin c gia tng tnh khng ca cc nhm khng sinh c tp trung ch yu vo 2 nhm khng sinh beta-lactam v aminoglycosid.

c) ng dng ch s PK/PD ngn nga khng thuc:

- ngn nga t bin khng thuc quan trng l m bo nng thuc trong mu ph hp c c Cpeak/MIC v AUC/MIC nh mong


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mun. Cc nghin cu cho thy cc gi tr PK/PD cn t c ngn nga chng t bin thng cao hn gi tr t hiu qu iu tr.

- V AUC/MIC:

+ Khi nghin cu ch s AUC/MIC ca khng sinh nhm quinolon, mt s nghin cu ch ra rng c th hn ch khng thuc bng cch tng ch s ny: ch s AUC/MIC t gi tr 100 ngn chn t bin khng thuc, trong khi nu ch s ny t 25-100 th c coi l nm trong ca s chn lc khng thuc. Tuy nhin, mt nghin cu in vitro khc cho thy AUC/MIC l 52 s lm gia tng chng khng, trong khi ch s ny t gi tr 157 th khng thy xut hin chng khng.

+ Mt s nghin cu in vitro cng chng minh liu thp ko di ca vancomycin vi AUC/MIC < 250 c lin quan n s pht trin khng ca cc chng S. aureus nhm II khng c gen iu ha agr, tuy nhin liu 750mg hoc 1g tng ng vi t s AUC/MIC l 382 hoc 510 khng cho thy s thay i trong tnh khng ca chng t cu ny. D liu ny cng ch ra kh nng to chng t bin do dng liu thp ko di vancomycin.

+ Tuy nhin gi tr AUC/MIC ngn nga chng khng cha thng nht gia cc nghin cu v cn thm cc nghin cu lm sng khng nh gi tr ny.

- V Cpeak/MIC:

+ Mt s nghin cu in vitro cho thy ch s Cpeak/MIC < 8 i vi cc quinolon c coi l mt yu t nguy c gy pht trin cc chng vi khun Gram-m khng khng sinh cn khi Cpeak/MIC >10 li c kh nng c ch qun th t bin khng thuc v ngn nga t vong do pht trin chng khng trong iu tr.

+ Cc nghin cu in vitro vi enoxacin v netilmicin cng cho thy nu Cpeak/MIC < 8 c kh nng lm tng s chng vi khun t bin khng thuc.

+ Nh vy, cc nghin cu cho thy Cpeak/MIC thc s c vai tr tc ng n khng thuc trong liu trnh iu tr. Tuy nhin, gi tr ti u ca ch s ny rt khc bit gia cc nhm khng sinh v tu thuc vo tng cp khng sinh vi khun. Do vy, cn thm cc nghin cu lm r mi lin quan ca cc c ch khng khc nhau vi cc thng s ng hc ca thuc p dng ti u cc m hnh dc lc hc trong lnh vc ny.

B Y t | CC NGUYN TC S DNG KHNG SINH 46

CC NGUYN TC S DNG KHNG SINH

1. LA CHN KHNG SINH V LIU LNG

- La chn thuc khng sinh ph thuc hai yu t: ngi bnhngi bnh v vi khun gy bnh. Yu t lin quan n ngi bnhngi bnh cn xem xt bao gm: la tui, tin s d ng thuc, chc nng gan thn, tnh trng suy gim min dch, mc nng ca bnh, bnh mc km, c a d ng Nu l ph n: cn lu i tng ph n c thai, ang cho con b cn nhc li ch/nguy c. V vi khun: loi vi khun, nhy cm vi khng sinh ca vi khun. Cn cp nht tnh hnh khng khng sinh c la chn ph hp. Cn lu cc bin php phi hp lm gim mt vi khun v tng nng khng sinh ti nhim khun nh lm sch m, dn lu, loi b t chc hoi t khi cn.

- Chnh sch k n khng sinh nhm gim t l pht sinh vi khun khng thuc v t c tnh kinh t hp l trong iu tr. Vi nhng khng sinh mi, ph rng, ch nh s phi hn ch cho nhng trng hp c bng chng l cc khng sinh ang dng b khng.

- Liu dng ca khng sinh ph thuc nhiu yu t: tui ngi bnhngi bnh, cn nng, chc nng gan thn, mc nng ca bnh. Do c im khc bit v dc ng hc, liu lng cho tr em, c bit l tr s sinh v nh nhi c hng dn ring theo tng chuyn lun. Liu lng trong cc ti liu hng dn ch l gi ban u. Khng c liu chun cho cc trng hp nhim khun nng. K n khng liu s dn n tht bi iu tr v tng t l vi khun khng thuc. Ngc li, vi nhng khng sinh c c tnh cao, phm vi iu tr hp (v d: cc aminoglycosid, polypeptide), phi bo m nng thuc trong mu theo khuyn co trnh c tnh, do vy, vic gim st nng thuc trong mu nn c trin khai.

2. S DNG KHNG SINH D PHNG

- Khng sinh d phng (KSDP) l vic s dng khng sinh trc khi xy ra nhim khun nhm mc ch ngn nga hin tng ny.

- KSDP nhm gim tn xut nhim khun ti v tr hoc c quan c phu thut, khng d phng nhim khun ton thn hoc v tr cch xa ni c phu thut [10].

a) Ch nh s dng KSDP (Ph lc 2, 3):

- Phu thut c chia lm 4 loi: Phu thut sch, phu thut sch nhim, phu thut nhim v phu thut bn (theo ph lc).

- KSDP c ch nh cho tt c cc can thip phu thut thuc phu thut sch nhim.


-Trong phu thut sch, liu php khng sinh d phng nn p dng vi

mt s can thip ngoi khoa nng, c th nh hng ti s sng cn v/hoc

chc nng sng (phu thut chnh hnh, phu thut tim v mch mu, phu thut

thn kinh, phu thut nhn khoa)

- Phu thut nhim v phu thut bn: khng sinh ng vai tr tr liu.

KSDP khng ngn nga nhim khun m ngn nga nhim khun xy ra

khng pht trin.

b) La chn khng sinh d phng:

- Khng sinh c ph tc dng ph hp vi cc chng vi khun chnh

thng gy nhim khun ti vt m cng nh tnh trng khng thuc ti a

phng, c bit trong tng bnh vin

- Khng sinh t hoc khng gy tc dng ph hay cc phn ng c hi,

c tnh ca thuc cng t cng tt. Khng s dng cc khng sinh c nguy c

gy c khng d on c v c mc gy c nng khng ph thuc liu

(VD: khng sinh nhm phenicol v sunfamid gy gim bch cu min dch d

ng, hi chng Lyell).

- Khng sinh khng tng tc vi cc thuc dng gy m (VD

polymyxin, aminosid).

- Khng sinh t c kh nng chn lc vi khun khng khng sinh v

thay i h vi khun thng tr.

- Kh nng khuch tn ca khng sinh trong m t bo phi cho php t

nng thuc cao hn nng khng khun ti thiu ca vi khun gy nhim.

- Liu php khng sinh d phng c chi ph hp l, thp hn chi ph

khng sinh tr liu lm sng.

c) Liu khng sinh d phng: Liu KSDP tng ng liu iu tr mnh nht

ca khng sinh (Ph lc 2).

d) ng dng thuc

- ng tnh mch: Thng c la chn do nhanh t nng thuc

trong mu v m t bo.

- ng tim bp: c th s dng nhng khng m bo v tc hp

thu ca thuc v khng n nh

- ng ung: Ch dng khi chun b phu thut trc trng, i trng

- ng ti ch: Hiu qu thay i theo tng loi phu thut (trong phu

thut thay khp, s dng cht xi mng tm khng sinh)

e) Thi gian dng thuc

- Thi gian s dng khng sinh d phng nn trong vng 60 pht trc

khi tin hnh phu thut v gn thi im rch da.


- Cephalosporins tim tnh mch trong 3 5 pht ngay trc th thut v

t nng cn thit da sau vi pht.

- Vancomycin v ciprofloxacin cn phi c dng trc MT GI v

HON THNH vic truyn trc khi bt u rch da.

- Clindamycin cn c truyn xong trc 10 20 pht.

- Gentamicin cn c dng 1 liu duy nht 5 mg/kg ti a ha s

thm vo m v gim thiu c tnh. Nu ngi bnhngi bnh lc mu hoc

ClCr < 20 ml/pht, dng liu 2 mg/kg.

- i vi phu thut m ly thai, KSDP c th dng trc khi rch da

hoc sau khi kp dy rn gim bin chng nhim khun m.

- B sung liu trong thi gian phu thut:

+ Trong phu thut tim ko di hn 4 gi, cn b sung thm mt liu khng sinh.

+ Trong trng hp mt mu vi th tch trn 1500ml ngi ln, v trn 25ml/kg tr em, nn b sung liu KSDP sau khi b sung dch thay th. g) Lu khi s dng KSDP:

- Khng dng khng sinh d phng cho cc nhim khun lin quan n chm sc sau m v nhng nhim khun xy ra trong lc m.

- Nguy c khi s dng KSDP:

+ D ng thuc.

+ Sc phn v.

+ Tiu chy do khng sinh.

+ Nhim khun do vi khun Clostridium difficile.

+ Vi khun khng khng sinh.

+ Ly truyn vi khun a khng.

3. S DNG KHNG SINH IU TR THEO KINH NGHIM

- iu tr khng sinh theo kinh nghim khi cha c bng chng v vi khun hc do khng c iu kin nui cy vi khun (do khng c Labo vi sinh, khng th ly c bnh phm), hoc khi nui cy m khng pht hin c nhng c bng chng lm sng r rt v nhim khun.

- Phc s dng khng sinh theo kinh nghim l la chn khng sinh c ph hp nht gn vi hu ht cc tc nhn gy bnh hoc vi cc vi khun nguy him c th gp trong tng loi nhim khun.

- Khng sinh phi c kh nng n c v tr nhim khun vi nng hiu qu nhng khng gy c.

- Trc khi bt u iu tr, c gng ly mu bnh phm phn lp vi khun trong nhng trng hp c th iu chnh li khng sinh ph hp hn.


- Nn p dng mi bin php pht hin nhanh vi khun khi c th (Xem Chng II. i cng v vi khun hc) c c c s ng n trong la chn khng sinh ngay t u.

- Nu khng c bng chng v vi khun sau 48 gi iu tr, cn nh gi li lm sng trc khi quyt nh tip tc s dng khng sinh.

- Cn thng xuyn cp nht tnh hnh dch t v nhy cm ca vi khun ti a phng la chn c khng sinh ph hp.

4. S DNG KHNG SINH KHI C BNG CHNG VI KHUN HC

- Nu c bng chng r rng v vi khun v kt qu ca khng sinh , khng sinh c la chn l khng sinh c hiu qu cao nht vi c tnh thp nht v c ph tc dng hp nht gn vi cc tc nhn gy bnh c pht hin.

- u tin s dng khng sinh n c.

- Phi hp khng sinh ch cn thit nu:

+ Chng minh c nhim ng thi nhiu loi vi khun nn cn phi hp mi ph tc dng (c bit nhng trng hp nghi ng c vi khun k kh hoc vi khun ni bo).

+ Hoc khi gp vi khun khng thuc mnh, cn phi hp tng thm tc dng.

+ Hoc khi iu tr ko di, cn phi hp gim nguy c khng thuc (v d: iu tr lao, HIV).

5. LA CHN NG A THUC

- ng ung l ng dng c u tin v tnh tin dng, an ton v gi thnh r. Cn lu la chn khng sinh c sinh kh dng cao v t b nh hng bi thc n (


Bng I.8).

- Sinh kh dng t 50% tr ln l tt, t 80% tr ln c coi l hp thu ng ung tng t ng tim. Nhng trng hp ny ch nn dng ng tim khi khng th ung c. Vic chn khng sinh m kh nng hp thu t b nh hng bi thc n s bo m c s tun th iu tr ca ngi bnhngi bnh tt hn v kh nng iu tr thnh cng cao hn.

- ng tim ch c dng trong nhng trng hp sau:

+ Khi kh nng hp thu qua ng tiu ho b nh hng (do bnh l dng tiu ho, kh nut, nn nhiu).

+ Khi cn nng khng sinh trong mu cao, kh t c bng ng ung: iu tr nhim khun cc t chc kh thm thuc (vim mng no, mng trong tim, vim xng khp nng), nhim khun trm trng v tin trin nhanh.

Tuy nhin, cn xem xt chuyn ngay sang ng ung khi c th.


Bng I.8. Sinh kh dng ca mt s khng sinh ng ung

Khng sinh Sinh kh dng (%)

nh hng ca thc n n hp thu

Ampicilin

Amoxicilin

40

90

Lincomycin

Clindamycin

30

90

Erythromycin

Azithromycin

50

40

Tetracyclin

Doxycyclin

50

90

Pefloxacin

Ofloxacin

90

80

Ghi ch: Gim hp thu

Khng nh hng hoc nh hng khng ng k

6. DI T IU TR

- di iu tr ph thuc vo tnh trng nhim khun, v tr nhim khun v sc khng ca ngi bnhngi bnh. Cc trng hp nhim khun nh v trung bnh thng t kt qu sau 7 - 10 ngy nhng nhng trng hp nhim khun nng, nhim khun nhng t chc m khng sinh kh thm nhp (mng tim, mng no, xng-khp), bnh lao th t iu tr ko di hn nhiu. Tuy nhin, mt s bnh nhim khun ch cn mt t ngn nh nhim khun tit niu sinh dc cha bin chng (khong 3 ngy, thm ch mt liu duy nht).

- S xut hin nhiu khng sinh c thi gian bn thi ko di cho php gim c ng k s ln dng thuc trong t iu tr, lm d dng hn cho vic tun th iu tr ca ngi bnhngi bnh; v d: dng azithromycin ch cn mt t 3 5 ngy, thm ch mt liu duy nht.

- Khng nn iu tr ko di trnh khng thuc, tng t k xut hin tc dng khng mong mun v tng chi ph iu tr.

7. LU TC DNG KHNG MONG MUN V C TNH KHI S DNG KHNG SINH

- Tt c cc khng sinh u c th gy ra tc dng khng mong mun (ADR), do cn cn nhc nguy c/li ch trc khi quyt nh k n. Mc d a s trng hp ADR s t khi khi ngng thuc nhng nhiu trng hp hu qu rt trm trng, v d khi gp hi chng Stevens Johnson, Lyell ADR nghim trng c th dn ti t vong ngay l sc phn v. Cc loi phn ng qu


mn thng lin quan n tin s dng khng sinh ngi bnhngi bnh, do phi khai thc tin s d ng, tin s dng thuc ngi bnhngi bnh trc khi k n v phi lun sn sng cc phng tin chng sc khi s dng khng sinh.

- Gan v thn l 2 c quan chnh thi tr thuc, do s suy gim chc nng nhng c quan ny dn n gim kh nng thi tr khng sinh, ko di thi gian lu ca thuc trong c th, lm tng nng dn n tng c tnh. Do phi thn trng khi k n khng sinh cho ngi cao tui, ngi suy gim chc nng gan thn v t l gp ADR v c tnh cao hn ngi bnh thng.

- V tr bi xut chnh ch ni khng sinh i qua dng cn hot tnh. T Bng I.9 cho thy hai khng sinh c th cng mt nhm nhng c tnh dc ng hc khng ging nhau. c im ny gip cho vic la chn khng sinh theo c a ngi bnh.

- Cn hiu chnh li liu lng v/hoc khong cch a thuc theo chc nng gan thn trnh tng nng qu mc cho php vi nhng khng sinh c c tnh cao trn gan v/hoc thn.

- Vi ngi bnhngi bnh suy thn, phi nh gi chc nng thn theo thanh thi creatinin v mc liu tng ng s c ghi mc Liu dng cho ngi bnhngi bnh suy thn.

- Vi ngi bnhngi bnh suy gan, khng c thng s hiu chnh nh vi ngi bnhngi bnh suy thn m phi tun theo hng dn ca nh sn xut, thng l cn c vo mc suy gan theo phn loi Child-Pugh.

Bng I.9. C quan bi xut chnh ca mt s khng sinh

Khng sinh V tr bi xut chnh

Cefotaxim

Cefoperazol

Thn

Gan

Lincomycin

Clindamycin

Gan

Gan

Erythromycin

Azithromycin

Gan

Gan

Tetracyclin

Doxycyclin

Thn

Gan

Pefloxacin

Ofloxacin

Gan

Thn

Nhng ni dung chnh trong cc nguyn tc trn c tm tt thnh nguyn tc MINDME (Bng I.10).


Bng I.10. Nguyn tc MINDME trong s dng khng sinh

M Microbiology guides wherever

possible

Theo ch dn vi khun hc bt k khi no c th

I Indication should be evidence-based Ch nh phi cn c trn bng chng

N Narrowest spectrum required La chn ph hp nht cn thit

D Dosage appropriate to the site and

type of infection

Liu lng ph hp vi loi nhim khun v v tr nhim khun

M Minimum duration of therapy Thi gian iu tr ti thiu cho hiu qu

E Ensure monotherapy in most situation Bo m n tr liu trong hu ht cc trng hp

KT LUN

iu tr thnh cng nhim khun ph thuc nhiu yu t, bao gm tnh trng bnh l, v tr nhim khun v sc khng ca ngi bnh. Cc kin thc v phn loi khng sinh, v PK/PD s gip cho vic la chn khng sinh v xc nh li ch liu ti u cho tng nhm khng sinh, l c s thc hin cc nguyn tc s dng khng sinh hp l. y cng l nhng ni dung quan trng i vi mi thy thuc bo m hiu qu - an ton - kinh t v gim t l khng khng sinh trong iu tr.

TI LIU THAM KHO

1. Antibiotic Expert Group (2010), Principles of antimicrobial use, in: Therapeutic

Guidelines: Antibiotic, Melbourne (pp. 1 28).

2. Andes D., Craig W. A. (2002), Animal model pharmacokinetics and pharmacodynamics: A

critical review. Int J Antimicrob Agents,19(4): pp 261-268.

3. Bergman S. J., et al.(2007), Pharmacokinetic and pharmacodynamic aspects of antibiotic

use in high-risk populations, Infect Dis Clin North Am, pp 821-846.

4. Bennett P. N., Brown M. J. (2003), Antibacterial drugs, Churchil Livingstone

5. British National Formulary 64th (2012), Chapter 5. Infection Antibacterial Drugs, Royal Pharmaceutical Society.

6. Goodman & Gilman's Pharmacology (2011), General Principles of Antimicrobial Therapy,

The McGraw-Hill Companies.

7. Jacobs M. R.(2001), Optimisation of antimicrobial therapy using pharmacokinetic and

pharmacodynamic parameters, Clin Microbiol Infect, 7(11) 589-596.

8. Lampiris H.W, Maddix D.S (2009), Clinical Use of Antimicrobial Agents, in:Basic &

Clinical Pharmacology (Bertram G. K. Masters S. B., Trevor A.J.), The McGraw-Hill

Companies.

9. Nightingale C.H, et al.(2007), Antimicrobial Pharmacodynamics in Theory and Clinical

Practice, Informa healthcare, New York.


10. Eugnie Bergogne-Brzin Pierre Dellamonica; (2004), Antibiothrapie en practique

clinique.

11. Network Scottish Intercollegiate Guidelines, Antibiotic prophylaxis in surgery. 2014

B Y t | 56

Chng II. i cng v vi khun hc

B Y t | I CNG V VI KHUN HC 57


I CNG V VI KHUN HC

Th gii sinh vt bao gm ng vt, thc vt v sinh vt n bo (protista); v kch thc nh b ca chng nn ngi ta thng gi chung l vi sinh vt. Da vo cu to chng c chia thnh 2 loi: Vi sinh vt bc cao v vi sinh vt bc thp. Vi sinh vt bc cao l nhng t bo c nhn tht (Eucaryota, ging t bo ng hoc thc vt) bao gm nm v ng vt nguyn sinh. Vi sinh vt bc thp tri li, c tin nhn (Procaryota, khng c mng nhn) bao gm vi khun v to lam (khng gy bnh). Virus l vi sinh vt nh hn v cu to n s hn na tc khng phi l t bo m ch l nhng ht c chc nng sng - nhn ln (sinh sn) khi trong nhng t bo sng. Bi ny ch gii thiu v vi khun.

1. KHI QUT V VI KHUN

a) ln: rt nh (ng knh thn thng t 0,5 n 1m v chiu di t 2

n 5m); n v tnh ln ca vi khun l micromet, vit tt l m (10-6 m hay 10

-3 mm).

b) Hnh th: c 3 loi hnh th chnh l hnh cu (gi l cu khun; v d: t cu, lin cu, ph cu, lu cu, no m cu), hnh ng (gi l trc khun; v d E. coli, m xanh, than, un vn) v hnh cong mm mi xon l xo (gi l xon khun; v d giang mai). Ngoi ra, c mt s hnh dng khc nh: trc khun ngn gi l cu trc khun nh vi khun dch hch hoc trc khun cong cng hnh helix nh Helicobacter pylori hay hnh du phy nh vi khun t.

c) Tnh cht bt mu: v vi khun rt nh nn phi nhum cho chng c mu rc r mi c th pht hin c hnh th ca chng di knh hin vi phng i 1000 ln.

- Nhum Gram: l phng php nhum quan trng, c p dng cho phn ln cc loi vi khun v h tr c lc cho vic chn on & iu tr sm bnh nhim khun. Nhum Gram va gip ta nhn nh c hnh dng ca vi khun, va phn bit c n l Gram-dng hay Gram-m; t ta c hng chn khng sinh thch hp dit vi khun nghi ng l tc nhn gy bnh. V d, nu tc nhn gy bnh nghi ng l vi khun Gram-dng th nn chn nhng khng sinh c ph tc dng chn lc trn Gram-dng nhiu hn nh penicilin G hoc cephalosporin th h 1; ngc li nu vi khun gy bnh nghi ng l trc khun Gram-m th nn chn amoxicilin hay cephalosporin th h 3 hoc nhm aminosid. S khc bit c bn gia vi khun Gram-dng v Gram-m l cu trc vch ca t bo (cell wall).

- Nhum Ziehl-Neelsen l phng php nhum dnh ring cho cc vi khun khng cn v acid (do vch c cha nhiu lipid v acid mycolic) nh vi khun lao, phong.

d) Tnh cht chuyn ha: da vo nhu cu oxy t do cho qu trnh chuyn ha, ngi ta chia vi khun thnh cc loi sau:


- Hiu kh bt buc (obligate aerobe): c oxy mi pht trin tt, v d trc khun m xanh, phy khun t

- K kh bt buc (obligate anaerobe): ch pht trin c trong iu kin hon ton hoc gn nh hon ton khng c oxy; thm ch gp oxy t do l cht, v d trc khun un vn, hoi th sinh hi, Bacteroides

- Hiu k kh ty tin (facultative anaerobe): pht trin c c khi c hay khng c oxy, v d cc trc khun ng rut (E. coli, thng hn, l) t cu, lin cu

- Vi hiu kh (microaerophile): cn mt lng nh O2 v nhiu CO2 hn, v d lu cu, ph cu, trc khun Haemophilus influenzae

2. CU TO T BO VI KHUN

Hnh I-3. S cu to t bo vi khun

- Bn thnh phn cu to quan trng t ngoi vo trong ca t bo vi khun l:

+ Vch (cell wall): b khung murein ca vch l do peptidoglycan to thnh. vi khun Gram-dng b khung ny gm nhiu lp peptidoglycan xp ln nhau; Gram-m ch l 1 lp peptidoglycan nhng li c 1 mng ngoi c cu to phc tp bao bc. Vch c nhim v: to hnh dng & bo v c hc cho t bo v tham gia vo qu trnh sinh sn (nhn ln) ca t bo.

+ Mng bo tng (plasma membrane) c chc nng thm thu chn lc.

+ Bo tng vi rt nhiu ribosome l ni sinh tng hp protein - cc enzym v thnh t thit yu cho qu trnh sinh trng v pht trin ca t bo.

+ Acid nucleic gm nhim sc th - vng nhn (ADN) v cc phn t ADN ngoi nhn (plasmid); ADN cha mt m di truyn (gen) qui nh cc c tnh ca t bo. Plasmid c th t truyn c cc gen ca n t t bo ny sang t bo khc. ng lu l: trn nhim sc th v plasmid c th tn ti


transposons gen nhy (on ADN c th nhy t nhim sc th vo plasmid v ngc li hoc t plasmid ny sang plasmid khc).

- Bn thnh phn cu to c bn nu trn cng chnh l 4 v tr tc ng ca thuc khng sinh trn t bo vi khun.

3. H VI KHUN C TH NGI BNH THNG

a) Vi h bnh thng ngi

- Khi nim:

+ Nhng qun th vi sinh vt c tr trn da v nim mc cc hc t nhin ca c th ngi gi l vi h bnh thng (normal microflora normal microbiota). Hu ht nhng qun th vi sinh vt l vi khun nn ngi ta cn gi chng l h vi khun bnh thng (normal bacteriaflora).

+ Trn da v nim mc cc hc t nhin - khoang rng c tip xc vi mi trng bn ngoi ca c th nh ming, mi, hng, m o, lun c rt nhiu vi sinh vt c tr; n bao gm: nhng vi sinh vt c mt thng xuyn (resident) ti v nhng vi sinh vt ch c mt thong qua (transient). Mt s phn ca c th nh mu, dch no ty, cc m, cc c quan ni tng do cu trc v hng ro min dch, iu kin bnh thng hon ton khng c vi sinh vt.

- S lng: ty tng v tr trn c th m s lng v chng loi vi sinh vt c khc nhau (Hnh I-4).

+ S lng cc loi v s lng c th ca tng loi vi khun thuc vi h bnh thng ti mi a im thng khng c nhn nhn ng. Trong thc t, v d da c ti 106/cm2; trong khoang ming c ti 109/ml nc bt; i trng c ti 1011/gam phn kh v trong dch m o c ti 107/ml dch. S lng vi khun trong t trng (duodenum) v hng trng (jejunum) c t hn, ch khong


Hnh I-4. Vi h bnh thng c th ngi

b) Vai tr ca vi h bnh thng

- Nhng vi sinh vt lun c tr trn b mt ca c th l nhng vi sinh vt hi sinh (commensal), chng khng hn c li v cng khng hn c hi. Chng sinh sn nhiu hay t ph thuc vo nhiu yu t sinh l khc nhau nh nhit , m v mt s cht dinh dng hay c ch nht nh. Cho s sng ca c th th khng quan trng, nhng mt s vng ca c th th vi h bnh thng ng vai tr nht nh trong vic gi thng bng cho sc khe v chc nng bnh thng ca c th.

- trong ng rut, cc thnh vin ca vi h sinh tng hp vitamin K v h tr cho vic hp thu thc n. Trn nim mc v da, cc vi sinh vt c tr thng xuyn c tc dng ngn cn s tn ti v xm ln ca vi sinh vt gy bnh, c th do c ch cnh tranh sinh hc.

- bt k ni c tr no cng tn ti nhng vi sinh vt c th gy bnh (facultative pathogen) khi c c hi, l khi mi trng thay i hoc do b


chn thng v chng xm nhp c vo m hoc vo mu. V d, lin cu c tr hng v ng h hp trn; nhng khi mt s lng ln vi khun vo mu (do tn thng ti ch) c th gy bnh vim ni tm mc (endocarditis). Bacteroides l c dn i trng th v hi, nhng nu chng xm nhp vo bng hoc do chn thng chng cng cc vi khun khc xm nhp vo m s gy nn nhng nhim khun c m v c th dn n nhim khun mu.

- Nh vy, cc vi sinh vt thuc vi h bnh thng cn c coi l nhng tc nhn gy bnh c hi (opportunistic pathogens). Cn ch iu ny chn khng sinh ph hp khi dng khng sinh d phng trong cc phu thut sch; v d: t da, vi khun ng hng u c th gy nhim khun sau m l t cu vng th ta chn cephalosporin th h 1; t ng tiu ha, thng l do cc trc khun Gram-m (h Enterobacteriaceae) th chn cephalosporin th h 3.

- ng lu : mi mt iu tr bng khng sinh l mt ln tc ng vo s cn bng ca vi h bnh thng: vi khun nhy cm b tiu dit, di p lc chn lc, nhng vi sinh vt khng khng sinh (ang s dng) c gi li, sinh sn mnh (qu sn) thay th nhng vi khun b tiu dit, lm mt cn bng cho i sinh vt c th ngi. Mt cn bng trong vi h bnh thng cng c th pht trin thnh bnh, v d ri lon tiu ha sau khi dng khng sinh ph rng ng ung di ngy hoc vim i trng gi mc do Clostridium difficile hoc b vim m o do nm sau khi t khng sinh khng khun di ngy.

Kt lun: ch dng thuc khng khun khi c nhim khun do vi khun gy ra v phi gim st din bin ngi bnh trong qu trnh iu tr bng khng sinh (khng ch theo di hiu qu dit vi khun gy bnh m cn c nhng nh hng khng mong mun ca thuc ti c th & vi h bnh thng)!

B Y t | VAI TR CA VI SINH LM SNG VI S DNG KHNG SINH HP L

63

VAI TR CA VI SINH LM SNG VI S DNG KHNG SINH HP L

I. MT S KHI NIM

Nhim khun nhim vi sinh vt, trong c nhim khun vn ang l bnh hay gp nc ta. iu tr bnh nhim khun chng ta hin ang c rt nhiu sn phm thuc khng khun (antibacterial antibiotics) trn th trng. Nhm s dng khng sinh hp l cho tng ngi bnh bc s iu tr cn bit r tc nhn/vi khun gy bnh l g v nhy cm ca chng vi khng sinh ra sao c th la chn c loi thuc c tc dng tt nht trn vi khun gy bnh v t gy tc dng khng mong mun nht cho

huong dan su dung khangs in h

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