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  • 7/25/2019 Nguyn Tc S Dng Khng Sinh_yhocthuchanh2015

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    I. TNG QUAN

    II. LA CHN KHNG SINH

    iu tr khng sinh da trn s khc bit sinh ha gia ngi v vi sinh vt. Thuc khng sinhc hiu qu trong iu tr nhim trng bi chng c c tnh chn lc (selective toxicity), tc lcc khng sinh c kh nng km hm, tiu dit vi khn k sinh m khng lm tn thng t boc th. Trong hu ht cc trng hp, c tnh chn lc ca khng sinh ch mang tnh tngi, nng thuc khi s dng phi m bo kim sot nhim khun v c th bnh nhnvn dung np c.

    la chn mt khng sinh thch hp nht trong iu tr cn phi bit:1.Loi vi khun gy bnh

    2. nhy cm ca vi khun vi cc khng sinh 3.V tr nhim khun 4.C a bnh nhn 5.Tnh an ton ca khng sinh c chn

    6.Chi ph iu trTuy nhin trong nhiu trng hp, cn iu tr khng sinh theo kinh nghim (S dng thuctrc khi c kt qu khng sinh )

    A. Xc nh loi vi khun gy bnh

    c tnh ca loi vi khun gy bnh chnh l trung tm ca vic la chn khng sinh thch

    hp. Vic xc nh nhanh loi vi khun gy bnh i khi da trn kt qu php nhum Gram.Phng php ny c bit hiu qu khi cn xc nh nhanh s hin din v cc c imhnh thi ca vi khun gy bnh trong cc dch c th: Mu, huyt thanh, dch no ty, dchmng phi, dch bng, dch khp v nc tiu (trong iu kin sinh l cc dch ny vkhun). Tuy nhin, thng thng vic nui cy nhm xc nh chnh xc v nh gi tnhnhy cm ca vi khun vi cc khng sinh l cn thit.

    Nguyn l s dng khng sinhJamie Kisgen - Lippincott Illustrated Reviews: Pharmacology - Sixth EditionDch:V Tin Khoa

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    B. iu tr kinh nghim trc khi xc nh c vi khun gy bnh

    Da vo cc phn ngmin dch ca c th5

    Tm DNA hoc RNA 4

    Tm khng nguyn3

    Nui cy vxc nh 2

    Soi trc tip 1

    Hnh 1

    Mt s k thut thng dng trong phngxt nghim chn on bnh nhim khun

    Chnh v th, cn c cc mu nui cy vi khun trc khi bt uiu tr. Nu khng c cc mu nui cy ban u, ta khng th phnbit c khi cc mu nui cy sau ny khng pht hin ra vi khunth l tc dng ca khng sinh hay do khng c vi khun. Xc nhchnh xc cc vi khun gy bnh i hi cc k tht khc nhau trong

    cc phng xt nghim nh: tm khng nguyn, DNA hoc l RNA,phn ng vim c hiu hoc cc p ng min dch ca c th ivi vi khun gy bnh (Hnh 1)

    Trong iu kin l tng, cc khng sinh c s dng trong iutr nhim khun s c la chn sau khi xc nh c vi khungy bnh v xc nh c tnh nhy cm ca chng vi cc khngsinh. Tuy nhin trong nhng trng hp nng, nu chm tr bnhnhn c th t vong, cn c nhng ch nh ngay lp tc da trnkinh nghim iu tr.

    1.Thi im iu tr:Cc bnh nhn c nhim khun nng, cp

    tnh khng r nguyn nhn VD: Bnh nhn gim bch cu trungtnh (mt trong nhng i tng rt d nhim khun) hoc bnhnhn b vim mng no (vim cp mng ngoi bao ph pha ngoino hoc ty sng) - cn c iu tr ngay lp tc. Nu c th, ccch nh iu tr nn c a ra sau khi cc mu bnh phm c phn tch ti phng xt nghim, nhng trc khi c kt qukhng sinh , cn a ra cc iu tr tc thi.

    2.La chn khng sinh:Vic la chn khng sinh khi cha c ktqu khng sinh s da vo v tr nhim khun, bnh s (v d nhcc nhim trng trc y, tui, lch s di chuyn gia cc vng al, cc khng sinh thng s dng, tnh trng min dch, nhimtrng xy ra ti bnh vin hay cng ng). Cc khng sinh ph rng

    c ch nh trong trng hp cha r loi vi khun gy bnh hocbnh nhn c biu hin nhim nhiu loi vi khun. La chn khngsinh cng c th da trn cc chng vi khun hay gy ra mt sbnh cnh lm sng nht nh. V d: cu khun Gram (+) trong dchno ty tr s sinh th hu ht khng phi l Streptococcus pneumo-niae m hu ht l Streptococcus agalactiae ( Mt type lin cunhm B), loi vi khun ny nhy cm vi Penicillin G. Tri li, cukhun Gram (+) trong dch no ty bnh nhn khong 40 tuithng l S. pneumonia. Loi vi khun ny thng khng penicillinG v phi iu tr bng Cephalosporin th h 3 ( Vd: Ceftriaxone)hoc Vancomycin.

    C. La chn khng sinh da vo nhy cm ca vi khun:Sau khi nui cy, tnh nhy cm ca vi khun s nh hng chovic la chn khng sinh trong iu tr. Mt vi loi vi khun, VD:Streptococcus pyogenes v Neisseria meningitides thng nhycm vi mt s loi khng sinh nht nh. Tri li, hu ht cc loitrc khun Gram m, Enterococci v cc chng t cu tnh nhycm thng kh d on v cn kt qu khng sinh la chnkhng sinh iu tr. Nng c ch ti thiu (MIC), nng ditkhun ti thiu (MBC) c th xc nh bng thc nghim ( Hnh 2)

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    64 32 16 8 4 2 1 0.5

    1

    2

    Cc ng cha vi khun v cthmkhng sinh vi nng khc nhau

    nh lng vi khun sau khic 24h

    Nng khng sinh tng ng

    Nng khng sinhcao nht

    MBC l nng khng sinh thp nhttiu dit 99,9% vi khun ( trong v dny MBC = 32)

    3

    Bacterial growth

    64 32 16 8 4 2 1 0.5

    64 32 16 8 4 2 1 0.5

    No bacterial growth Bacterialgrowth

    MIC l nng thp nht ca khng sinhc ch s pht trin ca vi khun (trong vd ny MIC = 2)

    nh lng vi khun sau 24hcy chuyn trong mi trngkhng c khng sinh

    Hnh 2:Xc nh nng c ch ti thiu (MIC)v nng dit khun ti thiu (MBC)ca khng sinh

    Nng khng sinh

    thp nht

    Vi khun khng pht trinVi khunpht trin

    1. Khng sinh dit khun v khng sinh km khun:

    Khng sinh c phn loi thnh khng sinh km khun hoc khng sinh dit khun.Cc khng sinh km khun ngn chn s pht trin v nhn ln ca vi khun tronghuyt tng ( hoc nc tiu) mc liu c th c th dung np, do n ngn slan rng ca cc nhim khun, khi h min dch tn cng, bt gi v loi tr vi

    khun. Nu cc khng sinh ht tc dng trc khi h min dch loi tr cc vi khun,cc vi khun cn li c th tip tc pht trin v bt u mt t nhim trng th hai.Cc khng sinh dit khun c kh nng tiu dit vi khun vi nng thuc tronghuyt tng c th c th dung np c. Do hot tnh khng khun mnh hn, nncc khng sinh dit khun c la chn trong iu tr cc bnh nhim khun nnghoc cc bnh nhn suy gim min dch. Hnh 3: S pht trin ca vi khun b kmhm khi thm cc khng sinh km khun. iu ng ch l lng vi khun sngvn duy tr d thm khng sinh km khun trc . Tri li, khi thm cc khngsinh dit khun, tng s lng vi khun sng gim xung r rt. Trong thc hnh lmsng, s phn loi ny ch mang tnh tng i, mt khng sinh c tc dng kmkhun vi chng vi khun ny nhng li c tc dng dit khun khi tip xc vi chngvi khun khc. VD: Linezolid c tc dng km khun vi S. aureus v Enterococci

    nhng c tc dng dit khun vi hu ht cc loi S. pneumoniea.2. Nng c ch ti thiu ( MIC The minimum inhibitory concentration )

    Nng c ch ti thiu l nng khng sinh thp nht c ch s pht trin ca vikhun trong 24h iu kin nui cy. iu ny gip xc nh tnh nhy cm (in vitro)ca vi khun v thng c dng trong thc hnh lm sng nhm nng cao hiuqu iu tr. H thng my tnh t ng gip tng chnh xc v gim thi gian xcnh MIC v y l phng php ph bin nht trong cc phng xt nghim lmsng.

    3. Nng dit khun ti thiu ( The minimum bactericidal concentration MBC)

    Nng dit khun ti thiu l nng khng sinh thp nht tiu dit 99,9% vi khunsau mt m trong mi trng nui cy ( Hnh 2) ( Lu : Trong lm sng him khixc nh MBC)

    D. La chn khng sinh da vo v tr nhim khun: vai tr ca hng ro mu no

    Mun c tc dng, khng sinh phi t c nng nht nh ti v tr nhim khun.Thuc c vn chuyn n cc m nh cc mao mch, cc mao mch ny c tnhthm khc nhau vi cc loi khng sinh khc nhau. Qu trnh vn chuyn thuc trongc th b nh hng bi cc ro cn t nhin (VD: Tuyn tin lit, nhau thai, dch thytinh v h thn kinh trung ng) c to thnh t h mao mch trong cc m. ccu to t mt lp t bo ni m, hng ro mu no ngn cc cht trong mu xmnhp vo no, tr cc cht c kch thc phn t nh v c bn cht thn du. Khnng xm nhp v nng ca cc khng sinh trong h thn kinh trung ng b nhhng bi cc yu t sau:

    1.Tnh thn du (Lipid solubility):y l mt yu t quan trng quyt nh kh nngthm nhp vo no ca thuc. Cc khng sinh c bn cht thn du nh Cloram-phenicol, Metronidazole d dng xm nhp vo h thn kinh trung ng, trong khi h-Lactam b ion ha pH sinh l, t tan trong lipid, v vy chng gn nh khng quahng ro mu no trong iu kin bnh thng. Khi mng no b vim, khng mnhn c chc nng mt cch trn vn, tnh thm tng, mt s khng sinh h-Lactam c th i qua, t nng c tc dng trong h thn kinh trung ng.

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    Thi gian

    Slng

    vikh

    un

    106

    105

    104

    103

    102

    Nhm chng(khng c thuc)

    Thm khng sinh

    Thm KS km khun

    (VD:chloramphenicol)

    Thm KS dit khun (VD: Penicillin)

    Hnh 3

    nh hng ca khng sinh dit khunv khng sinh km khun ln s phttrin ca vi khun

    2.Khi lng phn t:Cc khng sinh c trng lng phn tthp c th i qua hng ro mu no, ngc li, cc thuc ctrng lng phn t cao (nh Vancomycin) kh nng thmnhp rt km, ngay c khi mng no b vim

    3.Kh nng lin kt vi protein:Thuc dng t do khng linkt vi protein huyt tng l yu t quan trng hn quytnh vic xm nhp vo h thn trung ng so vi tng lngthuc hin din (dng t do + dng lin hp vi protein huyttng). Do cc thuc c mc lin kt protein huyttng cao kh nng thm nhp vo thn kinh trung ng sb gim.

    E. C a bnh nhn:

    Trong la chn khng sinh, phi ch nhiu n yu t ca bnh nhn nh: tnh trng h min dch, chc nng gan,thn, tun hon, tui Ph n c thai, cho con b cng lnhng i tng cn thn trng khi ch nh khng sinh.

    1.H min dch:Vic loi tr cc vi khun gy bnh ph thucvo tnh ton vn ca h min dch, y l h thng phngng gip c th loi tr cc vi sinh vt xm nhp. Nghinru, nhim HIV, mc i tho ng, ngi cao tui cngnh bnh nhn ang s dng cc thuc c ch mindchc th nh hng n chc nng min dch ca cth. Nhm bnh nhn ny, cn s dng cc khng sinh dit

    khun liu cao, thi gian iu tr ko di.

    2.Suy thn:Suy thn c th gy tch ly thuc khi s dng mts khng sinh. Trong trng hp ny, cn hiu chnh liu trnh tch ly thuc v cc tc dng ph. Creatinine huyttng l ch s thng dng nh gi chc nng thn vhiu chnh liu khng sinh. Tuy nhin, vi mt s khng sinh(VD: Vancomycine, Amyloglycoside) ngi ta thng xcnh trc tip nng thuc trong mu nhm xc nh gi trti a v/hoc ti thiu gip phng nga c tnh ca thuc.(Ch : S lng Nephron gim dn theo tui, do bnhnhn ln tui l i tng d b tch ly thuc khi s dng

    cc khng sinh thi tr qua thn).3.Suy gan:Cc khng sinh tch ly hoc thi tr ti gan (VD:

    Erythromycin, Docyxycline) phi c s dng thn trng cc bnh nhn suy gan.

    4.Gim ti mu vng nhim khun:Gim ti mu nmt s vng ca c th, v d vng chi di bnh nhn itho ng, lng khng sinh a n khu vc ny gim,cc nhim khun ti cc v tr ny s kh iu tr hn.

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    III. ng dng thuc

    NHM M T KHNG SINH

    Cha c nghincu RCT v nguyc trn ngi;Cc NC trnng vt chothynguy ctim tng

    c tnh trnng vt c xc nh,nguy c trnngi cha r.

    c tnh trnngi cxc nh, cnnhc li ch nguyc khi dng

    c tnh trnthai nhi vt xali ch; chngch nh cho thaiph

    B

    C

    D

    X

    -Lactams-Lactams with

    inhibitorsCephalosporinsAztreonamClindamycinErythromycinAzithromycinMetronidazoleNitrofurantoinSulfonamides

    ChloramphenicolFluoroquinolonesClarithromycinTrimethoprimVancomycinGentamicinTrimethoprim-sulfamethoxazole

    TetracyclinesAminoglycosides(except genta-micin)

    Khng gy hihoc c nguy ctim tng vi

    thai nhi

    A

    Hnh 4

    Cefazolin

    Clindamycin

    Linezolid

    Daptomycin

    Vancomycin

    Hnh 5

    So snh chi ph tng i ca mt s Ks dng iu tr S. aureus

    5.Tui: tr s sinh, chc nng thi tr ti gan v thn cha honthin, y l i tng d b c tnh khi s dng Cloramphenicolv Sulfamide. Bnh nhi cng khng nn s dng cc khng sinhTetracycline, khng sinh h Quinolones, cc khng sinh ny nh

    hng n s pht trin xng, sn tr nh. i vi bnh nhnln tui, chc nng gan, thn thng suy gim, thng s dcng hc ca mt s khng sinh cng v th thay i theo.

    6.Ph n mang thai v cho con b:Nhiu khng sinh qua hngro nhau thai xm nhp vo c th thai nhi, mt s khc i vo cth tr qua ng sa m. Hnh 4 tm tt v phn nhm cc khngsinh theo nguy c khi dng cho thai ph ca FDA. Cc thuc trongbng khng bao gm tt c khng sinh m ch mang tnh i din.Nng khng sinh trong sa m thng thp, nhng tng liu mtr nhn c qua sa m c th gy ln cc tc dng btli.

    7.Yu t nguy c ca nhim vi khun a khng: Trong nhimkhun a khng, iu tr ban u theo kinh nghim cn s dng ccloi khng sinh ph rng. Yu t nguy c ca nhim khun akhng bao gm: iu tr khng sinh trn 90 ngy, nm vin trn 2ngy trong vng 90 ngy trc khi pht hin nhim khun, nmvin trn 5 ngy, khu vc sng hoc bnh vin ti khu vc angsng c tn sut khng thuc cao, bnh suy gim min dch hocs dng thuc c ch min dch.

    Bng phn loi khng sinh thenguy c trn thai nhi ca FDA

    F. Tnh an ton ca khng sinh

    Nhm -Lactam l mt trong nhng khng sinh an ton nht nh tcdng chn lc trn vi khun. Mt s khng sinh khc (VD: Clorampheni-

    col) tc dng t chn lc hn c th gy c tnh nng n trn bnhnhn do thng ch c dng trong cc nhim khun nng e datnh mng ( Ch : c tnh ca khng sinh khng ch lin quan n ccc tnh t nhin ca thuc m yu t c a bnh nhn cng c thdn n c tnh khi dng thuc).

    G. Gi thnh:

    Mt vi khng sinh thng dng cho thy hiu qu tng t nhau khiiu tr nhim khun nhng gi thnh li khc nhau rt xa. V d, trongiu tr t cu khng Methicillin (MRSA) thng s dng mt trong cckhng sinh sau y: Vancomycin, Clindamycin, Daptomycin hocLinezolid. Mc d vic la chn khng sinh thng xem yu t sau ltrung tm: v tr nhim khun, mc trm trng ca nhim khun,

    bnh nhn c kh nng ung thuc hay khngnhng gi thnh cngl mt yu t quan trng cn xt n. Bng 37.5 m t tng i githnh ca mt s khng sinh dng iu tr t cu

    Khng sinh ng ung thng c dng cho cc nhim khun nh,c th iu tr ngoi tr. Do li th v kinh t, khng sinh ng ungcng c cn nhc s dng trong iu tr nhim khun nng.

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    V. PH KHNG KHUN

    VI. PHI HP KHNG SINH

    Mt s chng vi khun quantrng trong y khoa

    Isoniazid: khng sinh ph hp

    Tetracycline: khng sinh phrng

    Ampicillin: khng sinh phtrung bnh

    A

    B

    C

    D

    Escherichia coliHaemophilus influenzaeProteus mirabilisSalmonella typhi

    Listeria monocytogenes

    Actinomyces, Rickettsiae, Amoebae

    Mycobacteria

    Gram (+) bacill i

    Gram () cocci

    Gram (+) cocci

    Gram () cocci

    Anaerobic organisms

    Spirochetes

    Chlamydia

    Other

    Mycoplasma

    Gram (+) bacilli

    Gram () cocci

    Gram () rods

    Anaerobic organisms

    Spirochetes

    Chlamydia

    Gram (+) cocci

    Mycoplasma

    Gram (+) bacilli

    Gram () cocci

    Gram () rods

    Anaerobic organisms

    Spirochetes

    Chlamydia

    Other

    Gram (+) cocci

    Mycoplasm a

    Gram () rods

    Anaerobic organisms

    Spirochetes

    Chlamydia

    Other

    Mycoplasm a

    Gram (+) bacilli

    Gram () rods

    Other

    EnterococciGram (+) cocci

    Hnh 7A. Cc chng vi khun quan trng trong

    y hcB. Isoniazid , khng sinh ph hp

    Trong ni dung bi vit ny, cc loi vi khun quan trng trn lmsng c chia lm 8 nhm da vo php nhum Gram, c imhnh thi, tnh cht sinh ha v cc c tnh khc (Bng 37.7A).Trong 9 nhm , nhm khc dng ch tt c cc loi vi khunkhng thuc 8 nhm trn. Trong phn ny ( v nhng phn sau ^^)bng mu ny s dng m t ph tc dng ca cc khng sinh.

    A.Khng sinh ph hp:

    Khng sinh ph hp l cc khng sinh ch tc trn mt hoc giihn mt s nhm vi khun nht nh. VD: Isoniazide ch c tcdng trn trc khun lao (Mycobacterium tuberculosis) ( Hnh 7B)

    B.Khng sinh ph trung bnh:

    Khng sinh ph trung bnh l loi khng sinh c tc dng trn ccchng vi khun gram dng v cng c tc dng trn nhiu

    chng vi khun gram m. V d Ampicillin c tc dng trn cc vikhun gram dng v mt vi chng gram m (Hnh 7C)

    C.Khng sinh ph rng

    Cc khng sinh nh Tetracycline, Fluorquinolone, Carbapenemc tc dng trn rt nhiu chng vi khun khc nhau, chng cgi l cc khng sinh ph rng (Hnh 7 D).S dng cc khng sinhph rng c th lm thay i h vi khun t nhin trn c th, vc th dn n bi nhim v d nh bi nhim Clostridium difficile,s sinh trng ca loi vi khun ny bnh thng b gii hn bicc vi khun k sinh khc.

    Trong iu tr nhim khun, nn s dng mt khng sinh c hiunht cho loi vi khun ang nhim. iu ny gip gim kh nng binhim, gim t l khng v hn ch ti a c tnh. Tuy nhin trongmt vi trng hp cn phi phi hp khng sinh, v d phi hpthuc trong iu tr lao.

    A.u im ca phi hp thuc

    Vi loi khng sinh khi phi hp nh -Lactam v Amyloglycosidecho thy tc dng hip ng; tc l phi hp ny cho hiu quvt tri so vi vic s dng tng thuc ring r. Tc dng hipng gia cc khng sinh xy ra khng nhiu do phi hp

    nhiu thuc ch c s dng trong cc trng hp c bit (Vd: Khi cha r loi vi khun gy bnh hoc trong iu tr vim nitm mc do Enterococcal)

    B.Nhc im ca phi hp thuc

    Mt s khng sinh ch pht huy tc dng khi vi khun ang nhnln. Do , khi s dng cc khng sinh ny vi mt khng sinhkm khun khc lm hn ch tc dng ca thuc. VD: Tetracyclinelm gim tc dng dit khun ca Penicillin v Cephalosporin.Mt khc, phi hp khng sinh ba bi lm tng cc chng vikhun khng thuc.

    C. Ampicillin, khng sinh ph trungbnh

    D. Tetracyclline, khng sinh ph rng

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    VII. S KHNG THUC CA VI KHUN

    Sulfonamides

    Trimethoprim

    Vancomycin

    Macrolides Macrolides

    Clindamycin

    b-Lactams

    Chloramphenicol

    Fluoroquinolones

    Aminoglycosides Aminoglycosides

    Rifampin

    Khng thuc do thayi ch tc dng

    Gim tnh thm Tng thi trthuc

    Khng thuc do to ra enzymebt hot thuc

    b-Lactams

    Fluoroquinolones

    TetracyclineTetracycline

    Fluoroquinolones

    Tetracycline

    Macrolides

    b-Lactams

    Chloramphenicol

    Tetracycline

    Trc y,Tetracyclineiu tr Bacteroides rthiu qu, tuy nhin hinti vi khun ny khng thuc do to racc knh protein, ythuc khi t bo.

    Thay i enzyme ch,DNA gyrase,dn n ktqu fluoroquinoloneb khng

    -Lactam xm nhp vo vikhun Gram m nh l lcporin. Enterobacter khngCephalosporin do titenzyme -Lactamase, tuynhin vi khun cng c thkhng thuc bng cchthay i h thng knhporin lm thuc khngvo c t bo vi khun.

    Khng thuc do lm gim tch lythuc trong t bo vi khun

    -Lactamase (penicillinase)ph hy khng sinh bngcch thy phn vng lactam.Hin nay lu cu(Neisseria gonorrhoeae)khng Penicillin rt mnhdo tit ra enzyme ny.

    Hnh 8

    Mt s c ch khng khng sinh.

    Vi khun c coi l khng thuc khi s dng khng sinh liu ti a c th c th dung np mvn khng lm gim mt na lng vi khun (halt their growth). Mt s loi vi khun khng tnhin vi mt s khng sinh, v d hu ht vi khun gram m u khng Vancomycin. Tuy nhin,cc loi vi khun thng khng khng sinh bng cch pht trin cc chng c c lc cao hn

    hoc to ra cc chng khng thng qua t bin, khng thu c v qua chn lc t nhin.Mt s loi vi khun c th khng nhiu loi khng sinh.

    A.Khng khng sinh do thay i thng tin di truyn

    S thay i tm thi hoc lu di cc thng tin di truyn ca vi khun dn n khng khngsinh. Khng khng sinh c th l do vi khun t bin DNA hoc thu nhn cc thng tin di truynt cc vi khun khc (Qua trao i plasmid Dch gi) ( Hnh 8)

    B.Thay i cc protein chc nng trong cc chng vi khun khng thuc

    Khng khng sinh c rt nhiu c ch, v d nh thay i ch tc dng, gim mc xm nhpca thuc bng cch gim tnh thm hoc to ra cc bm thi tr thuc, lm bt hot khng sinhbng cch tit ra cc enzyme bt hot thuc.

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    VIII. S DNG KHNG SINH D PHNG

    IX. TC DNG PH CA KHNG SINH

    iu tr d phng nhimlin cu c ch nh bnh nhn c tin s mcbnh thp tim. Nhngbnh nhn ny c th phi

    iu tr vi nm.

    Dng khng sinh dphng nhng bnhnhn phu thut rngming, s dng cc cquan nhn to nh vantim nhn to

    iu tr d phng lao vvim mng no cho nhngi tng phi tip xcnhiu vi bnh nhn.

    S dng khng sinh d phngtrc khi tin hnh phu thutgip gim t l nhim khunhu phu. D phng ch chiu qu d phng cc loivi khun thng gp,

    khng phi tt c tc nhngy bnh.

    1

    2

    3

    4

    Hnh 9

    Mt vi trng hp c ch nh s dng

    khng sinh d phng.

    1.Thay i ch tc dng: Thay ch tc dng ca thucthng qua t bin lm cho vi khun khng mt hoc mt vikhng sinh cng c ch tc dng. V d: S. pneumonia khng-Lactam bng cch thay i ch tc dng (l cc penicil-lin-binding protein), lm gim kh nng gn kt ca thuc vi

    ch tc dng.2.Gim tch ly thuc:Lm gim lng khng sinh a vo tbo vi khun hoc to ra cc bm thi tr thuc lm cho cckhng sinh khng t c nng cn thit v tr tc dng,khng th lm tn thng hoc tiu dit vi khun. V d: Vikhun gram m hn ch s xm nhp ca khng sinh, trong c -Lactam bng cch thay i s lng v cu trc knhporin ngoi mng t bo. S hin din ca cc bm thi trthuc cng lm hn ch s xm nhp ca khng sinh vo tbo vi khun, iu ny quan st thy Tetracycline.

    3.Tit ra cc enzyme bt hot khng sinh:vi khun khngkhng sinh c kh nng tit ra cc loi enzyme phn hy hoc

    bt hot khng sinh. Mt vi enzyme bt hot khng sinh: 1)-lactamase thy phn vng -lactam ca penicillin, cephalo-sporin v cc thuc lin quan; 2) Acetyltranferase gn thmnhm Acetyl vo cc khng sinh, enzyme ny bt hot Clor-amphenicol v Amyloglycoside; 3) Esterase thy phn vnglacton ca Macloride.

    Mt vi tnh hung lm sng, v d nh lm th tht, phu thutnha khoa cn s dng khng sinh d phng nhim khun (Hnh9). S dng khng sinh d phng ba bi c th dn n binhim v khng thuc, do ch s dng hn ch trong cctrng hp li ch em li vt tri hn so vi nguy c. Thigian s dng khng sinh d phng cng cn gim st cht chnhm hn ch khng thuc.

    Mc d cc khng sinh c c tnh chn lc trn vi khun, nhngiu y khng ng ngha vi vic n hon ton khng c tcdng ngoi trn c th. V d, thuc c th gy d ng hocgy c tnh khng lin quan n c ch tc dng.

    A.Phn ng qu mn

    Qu mn, d ng vi cc khng sinh hoc cht chuyn haca n xy ra kh thng xuyn. Penicillin mc d tng ian ton nhng c th gy ra cc phn ng qu mn nghimtrng, t ni m ay (pht ban) cho ti shock phn v. Bnhnhn c tin s b hi chng Steven-Johnson hoc hoi tthng b khi dng mt khng sinh tuyt i khng cdng li khng sinh . Qu mn, d ng vi khng sinhthm ch khng c thuc iu tr.

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    X. V TR TC DNG CA KHNG SINH

    SulfonamidesTrimethoprim

    ulfonamides

    Thuc khngchuyn ha

    PABA

    THFA

    TetracyclinesAminoglycosidesMacrolides

    c ch tng hpprotein

    Clindamycin

    Chloramphenicol

    FluoroquinolonesRifampin

    es Fluoro uinolones

    c ch chc nngv tng hp acidnhn

    IsoniazidAmphotericin B

    Polymyxins

    DNA

    Ribosomes

    MNG T BO

    mRNA

    -LactamsVancomycin

    -

    c ch tng hpthnh t bo

    Isoniazid

    Thuc tc dngtrn chc nngmng t bo.

    Linezolid

    Daptomycin

    Telavancin

    Fosfomycin

    Hnh 10

    Phn loi khng sinh theo v tr tc dng trn t bo vi khun (THFA = tetrahydrofolic acid; PABA = p-aminobenzoic acid.)

    B.c tnh trc tip

    Nng khng sinh cao c th gy c tnh trc tip ln t bo c th. V d, Amylogly-coside gy c tnh thnh gic do tc ng ln chc nng ca t bo c tai.

    C.Bi nhim

    iu tr khng sinh, c bit cc khng sinh ph rng hoc phi hp nhiu khng sinh cth lm thay i h vi khun ng h hp, ming, ng tiu ha, ng sinh dc,to iu kin cho cc vi khun c hi, nm, vi khun khng thuc pht trin. Khi binhim xy ra, cn iu tr li vi cc khng sinh c bit.

    Cc khng sinh c th c phn loi theo nhiu cch: 1)Da vo cu trc ha hc (VD: -Lactam v Amyloglyco -side); 2) Da vo c ch tc dng ( VD: Nhm c ch tnghp vch t bo); 3) Da vo i tng tc ng ca thuc( VD: Khng sinh khng nm, virus, khng sinh khngkhun)

    THNH T BO

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