KHNG SINH V C CH KHNG THUC CA VI KHUN

Mc tiu
1.Xc nh bn cht thuc KS, phn bit thuc KS vi cht st khun v cht ty u. 2.Nu c ch tc ng ca KS 3.Lit k cc h KS ch yu. 4.Gii thch c ch, ngun gc ca s khng thuc v nu cc bin php hn ch s khng thuc

Ni dung
1.i cng v thuc KS 2.C ch tc ng ca KS. 3.Xp loi KS 4.S khng thuc

LCH S KS
Gia TK 17, mt thy thuc hong gia Anh cha bnh bng cch dng ru p ln vt thng Cui TK 19 ti Anh, cc mu bnh m mc c dng cha vt thng 1928, Alexnder Flemming (BV Saint Mary, London) pht hin nm tit ra cht c tc dng dit khun -Nm Penicillium notatum -Cht c tc dng dit khun : penicillin

LCH S KS
1938, Ernst Boris Chain v Howard Walter Florey (H Oxford) bt u nghin cu tc dng iu tr ca penicillin 25/5/1940 th nghim thnh cng trn chut Edward Abraham nghin cu iu ch penicillin tinh cht 1943 d n sn xut penicillin c chnh ph M c bit ch

LCH S KS
1944, iu tr mt ca nhim trng bng penicillin tn # 200 USD 1945, Chain v Florey nhn gii Nobel y hc Thp k 40, tui th trung bnh ca ngi phng Ty tng t 54 ln 75 tui

LCH S KS
Mt s KS khc : Sulfonamid c Gerhard Domard (c) tm ra vo nm 1932 Streptomycin c Selman Waksman v Albert Schatz tm ra vo nm 1934 Ngy nay con ngi bit c khong 6000 loi KS, 100 loi c dng trong y khoa.

i cng
Thuc KS l nhng cht c tc ng chng li s sng ca VK, ngn VK nhn ln bng cch tc ng mc phn t, hoc tc ng vo mt hay nhiu giai on chuyn ha cn thit ca i sng VK hoc tc ng vo s cn bng l ha

i cng
Antobiotic Anti : chng li Biotic : s sng

i cng
KS c hiu : tc ng ln mt loi VK hay mt nhm VK nht nh KS ph rng : c hot tnh i vi nhiu loi VK khc nhau KS ph hp : c hot tnh i vi mt hay mt s t VK

i cng
Ngun gc T nhin Tng hp Bn tng hp

i cng
Cht st khun Cht ho hc Ph hy t bo VK t c hiu gy hi cho m sng ca c th Dng ngoi da Mt s c tc ng c ch VK VK c th phc hi tr li

i cng
Cht st khun Hiu qu dit khun ph thuc : Nng ha tan Nhit Thi gian tip xc

i cng
Cht kh khun Cht ha hc Tiu dit t bo VK Rt c hi cho c th Dng kh khun vt

C ch tc ng ca KS
c ch s thnh lp vch t bo c ch nhim v ca mng t bo c ch s tng hp protein c ch s tng hp acid nucleic

C ch tc ng ca KS
c ch s thnh lp vch t bo Chc nng ca vch t bo : Gi hnh dng c trng ca t bo VK Che ch cho t bo khi v di p lc thm thu cao bn trong t bo Lm khun mu tng hp vch mi

C ch tc ng ca KS
c ch s thnh lp vch t bo Khi s tng hp vch t bo b c ch VK Gr(+) bin thnh dng hnh cu khng c vch (proto-plast) VK Gr(-) c vch khng hon chnh (spheroplast) t bo d v mi trng c trng lc bnh thng

C ch tc ng ca KS
c ch s thnh lp vch t bo KS thuc nhm ny : Bacitracin Cephalosporin Cycloserine Penicillin Rostocetin Vancomycin

C ch tc ng ca KS
c ch s thnh lp vch t bo C ch : Giai on 1: -Thuc gn vo th th PBPs phong b transpeptidase ngn tng hp peptidoglycan -C 3 - 6 th th PBP -Nhng th th khc nhau c i lc khc nhau i vi mt loi thuc tc dng ca thuc khc nhau

C ch tc ng ca KS
c ch s thnh lp vch t bo C ch : Giai on 2 : Hot ha cc enzym t tiu ly gii t bo mi trng ng trng

C ch tc ng ca KS
c ch nhim v ca mng t bo Chc nng ca mng t bo : Thm thu chn lc Vn chuyn ch ng Kim sot cc thnh phn bn trong mng t bo

C ch tc ng ca KS
c ch nhim v ca mng t bo Mt s ton vn ca mng t bo i phn t v ion thot ra khi t bo t bo cht Mng t bo VK v vi nm d b ph hy bi mt s tc nhn

C ch tc ng ca KS
c ch nhim v ca mng t bo KS thuc nhm ny : Amphotericin B Colistin Imidazole Nystatin Polymycins

C ch tc ng ca KS
c ch nhim v ca mng t bo Imidazole lm suy yu s ton vn ca mng t bo vi nm bng cch c ch s tng hp lipid ca mng t bo Polymycins tc ng ln VK Gr (-) Polyenes tc ng ln vi nm

C ch tc ng ca KS
c ch s tng hp protein KS thuc nhm ny Chloramphenicol Erythromycins Lincomycins Tetracyclines Aminoglycosides

C ch tc ng ca KS
c ch s tng hp protein Aminoglycosides : Streptomycin G 1: thuc gn vo th th trn tiu n v 30S G 2 : phong b hot tnh ca phc hp u tin trong qu trnh thnh lp chui peptid G 3 : thng tin mRNA b c sai 1 acid amin khng ph hp

C ch tc ng ca KS
c ch s tng hp protein Aminoglycosides : Streptomycin G 4 : lm v cc polysomes thnh monosomes khng c chc nng tng hp protein

C ch tc ng ca KS
c ch s tng hp protein Tetracyclines Thuc gn vo tiu n v 30S / rib th ngn chn cc amino acid mi gn vo chui peptid mi c thnh lp

C ch tc ng ca KS
c ch s tng hp protein Chloramphenicol Thuc gn vo tiu n v 50S / rib th c ch peptidyltransferase ngn cc amino acid mi gn vo chui peptid mi thnh lp

C ch tc ng ca KS
c ch s tng hp protein Macrolides Thuc gn vo tiu n v 50S/ rib th ngn cn s thnh lp phc hp u tin tng hp chui peptid Lincomycins C ch ging nhm Macrolides

C ch tc ng ca KS
c ch tng hp acid nucleic Actinomycin Thuc gn vo DNA to nn mt phc hp c ch polymerase ngn s tng hp RNA (mRNA) Mitomycin Thuc gn vo 2 chui DNA ngn 2 chui tch ri ra khng sao chp c

C ch tc ng ca KS
c ch tng hp acid nucleic KS thuc nhm ny Actinomycin Mitomycin Nalidixic acid Novobiocin Pyrimethamin Rifampin Sulfonamides Trimethoprim

C ch tc ng ca KS
c ch tng hp acid nucleic Rifampin Thuc gn vo polymerase c ch tng hp RNA Nalidixic acid Phong b DNA gyrase c ch tng hp DNA

C ch tc ng ca KS
c ch tng hp acid nucleic Sulfonamides PABA l mt tin cht tng hp acid folic tng hp acid nucleic Sulfonamides c cu trc tng t PABA cnh tranh to nhng cht tng t acid folic nhng khng c chc nng cn tr s pht trin ca VK

C ch tc ng ca KS
c ch tng hp acid nucleic Trimethoprim
c ch

KS

dihydrofolic acid reductase

Dihydrofolic acid

tetrahydrofolic acid

Tng hp purines / DNA

Xp loi KS
KS c xp loi da trn tnh c hiu dc l Cc h KS : Sulfonamides B-lactamines Aminoglycosides Tetracyclines Chloramphenicol Macrolides Rifamycin Polypeotides Quinilones

S khng thuc
C ch khng VK sn xut enzym ph hy hot tnh ca thuc VK lm thay i kh nng thm thu ca mng t bo i vi thuc im gn ca thuc c cu trc b thay i VK thay i ng bin dng lm mt tc dng ca thuc VK c enzym b thay i

S khng thuc
VK sn xut enzym ph hy hot tnh ca thuc Staphylococci sn xut -lactamase khng penicillin G VK Gr (-) sn xut adenylase, phosphorylase, acetylase ph hy aminoglycoside VK Gr (-) sn xut chloramphenicol acetyltransferase khng chloramphenicol

S khng thuc
VK lm thay i kh nng thm thu ca mng t bo i vi thuc Tetracyclin tch t bn trong VK nhy cm Polymycins, Amikacin Mt s Aminoglycosides khc

S khng thuc
im gn ca thuc c cu trc b thay i VK t bin NST mt / thay i protein c bit trn tiu n v 30S mt im gn ca Aminoglycosides khng VK mt / thay i PBPs khng penicillin VK thay i th th trn tiu n v 50S / rib th khng Erythromycin

S khng thuc
VK thay i ng bin dng lm mt tc dng ca thuc VK s dng acid folic c sn VK khng cn cn PABA khng vi Sulfonamides

S khng thuc
VK c enzym b thay i Enzym b thay i vn cn chc nng bin dng nhng t b nh hng bi thuc VK nhy cm vi Sulfonamides : Tetrahydropteroic acid synthetase c i lc vi Sulfonamides cao hn nhiu so vi PABA.

S khng thuc
Ngun gc ca s khng thuc Khng do di truyn Do di truyn khng do NST khng ngoi NST

S khng thuc
Ngun gc khng do di truyn S nhn ln ca VK cn thit cho tc ng ca thuc -VK khng nhn ln c khng thuc -Nhng th h sau c th nhy cm tr li Mt im gn c bit dnh cho thuc

S khng thuc
Ngun gc do di truyn Phn ln VK khng thuc l do Thay i v mt di truyn Hu qu ca qu trnh chn lc bi thuc KS

S khng thuc
Ngun gc ca s khng thuc khng do NST t bin ngu nhin mt on gen kim sot tnh nhy cm vi thuc C ch chn lc Tn sut 10-7 10-12 Him xy ra : 10 20% Di truyn theo chiu dc

S khng thuc
Ngun gc ca s khng thuc khng ngoi NST Do cm ng vi KS Tn sut 10-6 10-7 Thng xy ra : 80 - 90% Di truyn theo chiu dc v chiu ngang

S khng thuc
Ngun gc ca s khng thuc Vt liu di truyn trn plasmid c truyn theo c ch : Chuyn th ( transformation) Chuyn np ( transduction) Chuyn v ( transposition) Giao phi ( conjugation)

S khng thuc
S khng cho Vk khng vi 2 hay nhiu loi thuc c cng c ch tc ng Thng gp nhng thuc c thnh phn ha hc gn ging nhau Polymycin B Colistin Erythromycin Oleandomycin Neomycin - Kanamycin

S khng thuc
S khng cho C th thy nhng thuc khng c lin h ha hc Erythromycin - Lincomycin

S khng thuc
Gii hn s khng thuc Duy tr liu lng thuc cao trong m Phi hp thuc Hn ch s dng

S khng thuc
S dng KS trong iu tr La chn KS da vo : Chn on Lm sng Cn lm sng Kh nng c on (kinh nghim) KS Th nghim tc ng dit khun trong huyt tng

S khng thuc
KS c ch nh trong trng hp : Tc nhn tm thy khng vi nhiu loi KS Nhim trng e da tnh mng Cn loi b nhanh chng VK ra khi c th

S khng thuc
Phi hp KS trong iu tr Ch nh : Nhim trng nng, suy gim MD Gim chng t bin khng thuc / nhim trng mn Nhim trng do nhiu loi VK phi hp Cn c tc dng hip ng dit khun Gim liu gim c tnh ca thuc

S khng thuc
Phi hp KS trong iu tr Bt li : Thy thuc ch quan Tng nguy c qu mn vi thuc Tng chi ph iu tr Hiu qu c th khng cao Xy ra tnh trng i khng

S khng thuc
Phi hp KS trong iu tr Hiu qu ca phi hp thuc : Hip ng : 1 + 1 > 2 Hp cng : 1 + 1 = 2 Khng thay i : 1 + 1 = 1 i khng : 1 + 1 < 1

Mt s phi hp thuc c tc dng hip ng

-lactamin + aminoglycoside Glycopeptid + aminoglycoside Sulfamide + trimethoprim -lactamin + fluoroquinolon Rifampicin + vancomycin

Mt s phi hp i khng cn trnh

Aminoglycoside + chloramphenicol Aminoglycoside + tetracyclin Quinolon + chlormphenicol Penicillin G / ampicillin + tetracyclin Penicillin G / ampicillin + macrolide