M100-S21

Qui trnh thao tc chun v th nghim tnh nhy cm khng sinh Tiu chun c kt qu khng sinh v MIC Phin bn cp nht ln th 21 (Nm 2011)

Ngi dch

1. ThS. DS. Th Thu Nga, OUCRU

Ngy ___/___/___

Ngi sa

1. PGS.TS. Phm Vn Ca, NHTD 2. BS. T Song Dip, HTD 3. ThS. DS. Ng Th Bch H, MoH 4. TS. on Mai Phng, BV Bch Mai 5. PGS.TS. Nguyn V Trung, NHTD 6. TS. Heiman Wertheim, OUCRU

Ngy ___/___/___ Ngy ___/___/___ Ngy ___/___/___ Ngy ___/___/___ Ngy ___/___/___ Ngy ___/___/___

Ngi ph duyt

TS. Nguyn Vn Knh Gim c-NHTD Ch tch GARP-Vit Nam

Ngy ___/___/___

M100-S21 Vin Tiu chun Lm sng v Xt nghim Cht lng vt tri trong th nghim chm sc sc khe Vin Tiu chun Lm sng v Xt ngim (CLSI tn c NCCLS) l mt t chc quc t, a ngnh, phi li nhun, chuyn pht trin cc tiu chun, v gio dc. Vin thc y s pht trin v s dng nhng tiu chun v hng dn trong vic to s ng thun t nguyn trong lnh vc chm sc sc khe. Vin c c th gii cng nhn v s p dng cc quy trnh c nht to s ng thun trong vic pht trin cc tiu chun v hng dn cho cc th nghim trn bnh nhn v nhng vn lin quan ti chm sc sc khe. Cc quy trnh ca vin da trn nguyn l m qu trnh to s ng thun l qu trnh hiu qu v c gi thnh tt cng c cc th nghim trn bnh nhn v chm sc sc khe. Xut Bn Ti liu ny c xut bn nh l mt tiu chun, hng dn, hoc bo co Tiu chun Ti liu ny c pht trin thng qua qu trnh to s ng thun. Qu trnh ny ng nht ha mt cch r rng nhng yu cu cn thit v c bit cho nguyn vt liu, phng php v s thc hnh cho vic s dng nhng quy trnh khng th thay i. Hng dn Ti liu ny c pht trin thng qua qu trnh to s ng thun. Qu trnh ny m t chi tit cc yu cu cho s thc hnh chung, quy trnh, hoc cc vt liu s dng khng bt buc. Hng dn ny c th c s dng nh dng c son tho ra hay c th thay i bi ngi s dng cho ph hp vi nhng mc ch cn thit c bit. Bo co Ti liu ny khng phi bnh duyt li qu trnh to s ng thun v c xut bn bi Hi ng y Tr. Qu Trnh To S ng Thun Qu trnh to s ng thun t nguyn ca CLSI l mt quy trnh thit lp nhng yu cu chnh thng cho: Quyn ca d n S pht trin v bnh duyt ti liu c tnh cht m S sa cha ti liu l s p ng li vi nhng phn hi t ngi s dng S chp thun ti liu l mt quy trnh to s ng thun chun hoc hng dn chun

M100-S21 Mi ti liu c thit k bao gm hai mc to s ng thun trnh v ph duyt. Da vo yu cu cho tng lnh vc nh gi hoc qu trnh thu thp d liu. Ti liu c th c son tho mc to s ng thun trung gian trnh Giai on u ca qu trnh ng thun ti liu l thc thi qu trnh bnh duyt bi cng ng cc nh nghin cu trong lnh vc chm sc sc khe. Qu trnh ny nh l mt tiu chun hay hng dn ang trong qu trnh trnh. Ti liu phi tip thu ton b nhng bnh xt chuyn mn bao gm s bnh xt bao qut v mc ch, cch tip cn, v li ch cng nh nhng bnh xt t m tng ni dung chuyn mn v nh dng vn bn. Chp thun Mt tiu chun hoc hng dn mun c chp thun phi thu c s ng thun trong cng ng cc nh nghin cu trong lnh vc chm sc sc khe. Qu trnh ny phi c sot xt nh gi li ch ca ti liu cui cng v bo m s ng thun t c (nhng ch gii trong ti liu mi nht phi tha mn nhng mc tiu t ra) v xc nh s cn thit cho s ng thun ti liu b sung. Tiu chun v hng dn ny ca chng ti i din cho mt quan im ng thun cho nhng s thc hnh tt v phn nh s tn thnh cn thit t nhng nh hng v mt vt cht, kh nng thc thi v quyn li ca bnh nhn thu c t nhng quy trnh to s ng thun c xc nh ca CLSI. Nhng iu khon trong tiu chun v hng dn ca CLSI c th nghim ngt hn hoc km nghim ngt hn cc quy nh trong cc vn bn lut php. Do , s chp hnh theo ti liu c ng thun mt cch t nguyn khng da vo trch nhim t nguyn ca ngi dung nh i vi cc vn bn ni quy. Phn Hi Nhng phn hi t ngi s dng l v cng cn thit cho qu trnh to s ng thun. Bt k ai mun phn hi xin r a ch theo nh quy trnh to s ng thun c t ra bi Hi ng c vit trong ti liu ny. Bt c phn hi no, bao gm c nhng phn hi ng gp vo s thay i ca vn bn trong n phm k tip hoc nhng phn hi khng to ra s thay i cho ti liu xin r a ch nh trong phn ph lc ca ti liu. Chung ti nhit lit khuyn khch ngi c gi phn hi v bt c phn no ca ti liu bt c phin bn no. a ch phn hi: Clinical Laboratory Standards Instittute, 940 West Valley Road, Suite 1400, Wayne, PA 19087, USA Tham Gia Tnh Nguyn CLSI hi thc cc chuyn gia trong lnh vc chm sc sc khe mi chuyn khoa tham gia tnh nguyn vo d n ca chng ti. Xin hy lin lc vi chng ti qua a ch customerservice@clsi.org hoc s in thoi +610.688.0100 c thm nhng thng tin t y ban.

M100-S21 Qui trnh thao tc chun v th nghim tnh nhy cm khng sinh; Phin bn cp nht ln th 21 M u Nhng thng tin trong ti liu ny nhm mc ch b sung cho nhng quy trnh chun v xc nh tnh nhy cm vi khng sinh c cng b trong nhng ti liu trc ca CLSI nh: M02-A10-Quy Trnh Chun cho Th Nghim Xc nh Tnh Nhy Cm Khng Sinh bng Phng php Khoanh Giy Khuch tn; v M07-A8- Xc nh Tinh Nhy Cm Khng Sinh bng Phng Php Pha Long i vi cc Vi Khun Hiu Kh. Tiu chun ny mang nhng thng tin v quy trnh chun cho th nghim bng c phng php khoanh giy v pha long cho cc vi khun hiu kh. Thng tin t cc Labo Vi sinh Lm sng cc k quan trng vi cc Bc s Lm sng trong vic iu tr cc bnh nhn nng. Kt qu ca th nghim tinh nhy cm khng sinh c gi tr lm sng khi th nghim c thc hin di iu kin ti u nht v Labo c kh nng cung cp nhng thng tin v nhng nhm khng sinh mi nht. Nhng thng tin dng bng trong ti liu ny th hin nhng thng tin mi nht trong quy trnh chun v la chn khng sinh, din gii kt qu khng sinh v m bo cht lng xt nghim trong M02 v M07. Ngi s dng phi thay th nhng bng c bng nhng bng mi ny. Nhng s thay i ny c th hin bng in m. Vin Tiu chn Lm sng v Xt nghim. Qui Trnh Thao Tc Chun v Th Nghim Tnh Nhy Cm Khng Sinh; Phin bn cp nht ln th 21. Ti liu ca CLSI M100-S21 (ISSBN 1-56238-742-1). Vin Tiu chun Lm sng v Xt nghim, 940 West Valley, Suite 1400, Wayne, Pennsylvania 19087 Hoa K, 2011 Nhng thng tin c din gii di dng bng trong ti liu ny ch c gi tr khi quy trnh c thc hin theo ng nh ti liu M02-A10 Quy Trnh Chun cho Th Nghim Xc nh Tnh Nhy Cm Khng Sinh bng Khoanh Giy; Tiu Chun c Chp Thun-Phin Bn Ln Th Mi v M07-A08 Phng Php Xc nh Tinh Nhy Cm Khng Sinh bng Pha Long vi Vi Khun Hiu Kh; Tiu Chun c Chp Thun-Phin Bn Ln Th Tm.

M100-S21 Tm tt quy trnh ca CLSI cho vic xc nh tiu chun din gii v nhng khong cho php ca qun l cht lng xt nghim Vin Tiu chun Lm sng v Xt ngim (CLSI tn c NCCLS) l mt t chc quc t, a ngnh, phi li nhun, chuyn pht trin cc tiu chun, v c chc nng gio dc. Vin c chng nhn bi Vin cc Tiu chun Quc gia Hoa K (American National Standards Institute). Vin thc y v pht trin vic s dng nhng tiu chun v hng dn c ng thun trong lnh vc chm sc sc khe. Nhng tiu chun v hng dn c ng thun c pht trin nhm vo nhng lnh vc quan trng ca cc th nghim chun on v chm sc sc khe, v c pht trin bi mt quy trnh to s ng thun m cng vi s tho lun. CLSI cu th mi c nhn v t chc quan tm ti lnh vc th nghim chun on v chm sc bnh nhn. Nhng thng tin v CLSI c th c tm thy ti www.clsi.org. y ban v th nghim tnh nhy cm khng sinh (Khng sinh ) ca CLSI tin hnh sot xt d liu t rt nhiu nghin cu v cc ngun khc nhau (v d, nghin cu in vitro, nghin cu dc ng hc, nghin cu lm sng) xc nh nhng phng php khng sinh , tiu chun din gii kt qu, v cc tham s cho qun l cht lng (QC). Nhng yu cu i vi cc d liu cho vic xc lp tiu chun din gii kt qu, cc d liu cho cc tham s ca QC, quy trnh ca vic cn nhc, nh gi cc d liu c trnh by trong ti liu CLSI-M23- Pht trin cc Tiu chun cho Th nghim Nhy cm Khng sinh v cc Tham s cho Kim sot Cht lng (Development of In Vitro Susceptibility Testing Criteria and Quality Control Parameters). Mc nhy cm ca vi khun vi khng sinh ngy cng suy gim, gy ln tnh trng khng hiu qu v/hoc thiu an ton cho lm sng. Cc phng php khng sinh v cc tham s QC cn phi c iu chnh m bo chnh xc hn, d dng thc hin hn. Chnh v nhng l do trn, CLSI lin tc gim st v cp nht thng tin co cc ti liu ca Vin. Mc d, cc tiu chun v hng dn ca CLSI c pht trin da trn nhng thng tin mi nht, nhng kin thc ph hp vi thi im hin hnh. Nhng vi nhng thay i lin tc trong lnh vc Khoa hc v Y-Sinh hc, nhng hng dn v tiu chun ny phi c p dng mt cch hi ha vi nhng iu chnh lm sng, sao cho, mi kt qu xt nghim phi ph hp v c gi tr trong vic iu tr bnh nhn ca tng trung tm. Nhng thng tin b sung, cp nht v cc thay i trong ti liu ny c tm thy ti phn ring ca y ban Th nghim Nhy cm Khng sinh theo s sau: trang nh www.clsi.org -> Committees -> Microbiology -> S/C Antimicrobial Susceptibility Testing.

M100-S21 Tuyn b v Nhim v ca y ban Th nghim Nhy cm Khng sinh y ban v th nghim nhy cm khng sinh c thnh lp bao gm cc i din t chuyn gia, chnh ph, v cng nghim, bao gm phng xt nghim vi sinh, c quan chnh ph, cung cp dch v chm sc sc khe v gio dc, dc phm v cng nghim chn on vi sinh. Bng quy trnh to s ng thun t nguyn ca CLSI, y ban pht trin nhng tiu chun m thc y s chnh xc trung th nghim khng sinh v s ph hp trong bo co kt qu khng sinh . Nhim v ca y ban Th nghim Nhy cm Khng sinh l: Pht trin cc phng php tham chiu chun cho cc th nghim nhy cm khng sinh. Cung cp cc tham s QC cho cc phng php th nghim chun. Xc nh tiu chun din gii kt qu cho cc th nghim nhy cm khng sinh chun. Cung cp nhng gi v chin lc th nghim v bo co m c gi tr lm sng v hiu qu kinh t. Lin tc iu chnh cc tiu chun v ti u ha s pht hin cc c ch khng mi ni t pht trin hoc ci tin cc phng php, tiu chun din gii kt qu, v tham s cho QC. Tuyn truyn cho ngi s dng cc tiu chun v hng dn thng qua cc knh truyn thng a phng tin. Khuyn khch s trao i vi ngi s dng v cc phng php.

Mc tiu thc tin cho nhim v ca y ban l cung cp nhng thng tin hu dng cc phng xt nghim c th h tr lm sng trong vic la chn liu php khng sinh ph hp iu tr bnh nhn. Nhng tiu chun v hng dn c ngha l cha ng y cc thng tin tng minh ca tt c cc khng sinh v phi tha mn cc tiu chun c ra bi CLSI. Gi tr dn ng cho nhim v ca y ban l cht lng, chnh xc, tng minh, thi gian, hp tc, ng thun, ang tin cy.

M100-S21 I. A. La chn khng sinh cho th nghim v bo co Vic la chn cc loi khng sinh ph hp nht cho th nghim v bo co l quyt nh do cc phng xt nghim vi sinh lm sng kt hp tho lun vi Bc s chuyn khoa Truyn nhim v khoa Dc, cng nh vi Hi ng Thuc v iu tr v Khoa Chng nhim khun ca bnh vin. Nhng khuyn co trong ti liu ny vi tng nhm vi khun cng vi cc khng sinh c chng minh hiu qu bng cc k thut in vitro. Qu trnh cn nhc nh gi cho tng nhm khng sinh th nghim/bo co da trn hiu qu lm sng, tnh trng khng khng sinh, gim thiu nguy c khng khng sinh, gi thnh, nhng ch dn s dng lm sng ca FDA, v nhng khuyn co chung mi nht v nhm khng sinh u tin v cc nhm khng sinh thay th. S khng thuc bt thng phi c bo co (v d Enterobacteriaceae khng vi carbapenems). Th nghim i vi cc loi thuc khng sinh chn lc c th s dng cho mc ch chng nhim khun. B. Cc khng sinh xp trong cng mt ch chng cng mt nhm khng sinh do gii thch kt qu (nhy cm, trung gian, khng) v hiu qu trn lm sng tng t.. Trong mi , hoc gia cc khng sinh thuc cng mt nhm khng sinh, ch kh nng khng cho hoc nhy cho gn nh l hon ton. C ngha l cc li ln khng qu 3% v cc li nh khng qa 10% tng s th nghim. Ngoi ra, khi khng nh rng t nht 100 chng khng li hoc vi nhm khng sinh c th nghim th kt qu l khng ch c th rt ra khi c trn 95% chng khng vi tt c cc khng sinh c th nghim. Ch hoc cu trn cn c th dng trong trng trng hp cng th nghim vi cc chng trn nhng kt qu thu c l nhy v kt qu din gii l nhy cm (v d cefotaxime hoc ceftriaxone vi Haemophilis influenzae). C th da trn kt qa th nghim i vi mt khng sinh suy ra kt qu i vi khng sinh cn li (v d, h vi khun ng rut (Enterobacteriaceae) khng sinh ESBL nhy cm vi cefotaxime c th suy ra cng nhy cm vi ceftriaxone). Do , kt qu thu c t th nghim vi cefotaxime c th c bo co cng vi ch thch i km trong bo co rng vi khun cng nhy cm vi ceftriaxone. Vi cc khng sinh khng thuc cng mt nhm hoc khng thuc cng mt , th nghim ca mt khng sinh khng th dng d on kt qu cho cc khng sinh khc lin quan, cn thc hin nhng th nghim ring r hoc thu thp thng tin.

C. 1.

Th nghim/Bo co theo nhm Trong bng 1A, 1B v 1C, cc khng sinh Nhm A l la chn thch hp cho c th nghim thng qui, cc khng sinh u tin ln bo co thng qui cc kt qu i vi mt s vi khun c th thng gp.

2.

M100-S21 Nhm B gm cc khng sinh gip cng c th nghim u tin. Tuy nhin bo co cc kt qu mt cch chn lc v d nh vi khun khng cc khng sinh trong nhm A. Ch dn khc cho vic bo co kt qu c th bao gm cc loi bnh phm c bit (v d cephalosporin th h 3 dng cho trc khun gy bnh ng rut phn lp t dch no tu hoc trimethoprim-sulfamethoxazole dng cho cc vi khun phn lp t nc tiu), a nhim, nhim nhiu v tr, cc trng hp bnh nhn b d ng thuc, khng dung np thuc, khng p ng vi cc khng sinh trong nhm A hoc dng cho mc ch chng nhim khun.

3.

Nhm C bao gm cc khng sinh thay th hoc b sung. Nhng khng sinh ny i hi phi th nghim nhng bnh vin cha cc cn nguyn vi khun khng li nhiu loi khng sinh hng u (c bit l cng nhm, v d cc khng sinh nhm -lactam hoc nhm aminoglycoside), hoc dng trong iu tr i vi cc bnh nhn c tin s khng mt s thuc thuc nhm u tin, hoc iu tr cc vi khun bt thng (v d, cloramphenicol iu tr Salmonella spp., phn lp ngoi rut hoc mt s chng khng vancomycin) hoc bo co Khoa Chng nhim khun nh mt bin php h tr v mt dch t hc.

4.

Nhm U (Urine-nc tiu) bao gm mt s loi khng sinh nht nh (v d nitrofurantoin v cc quinolone) thng ch dng trong iu tr nhim trng tit niu Nhng khng sinh ny khng c php bo co thng qui vi cc cn nguyn vi khun phn lp c t ngoi ng tit niu c kh nng cha tr. Cc khng sinh ph rng c th c cho vo nhm U trong iu tr cc tc nhn gy vim ng tit niu (v d, Pseudomonas aeruginosa v ofloxacin).

5.

Nhm O (Other-khc) gm cc khng sinh c ch nh lm sng i vi mt nhm vi khun, nhng thng khng phi l la chn cho th nghim cng nh bo co thng qui Hoa K.

6.

Nhm Inv (Investigational-nghin cu) gm cc khng sinh ang trong qu trnh nghin cu, cha c FDA thng qua s dng Hoa K.

D.

Bo co chn lc Mi phng th nghim phi quyt nh la chn khng sinh no trong cc bng cho bo co thng qui (nhm A), v khng sinh no ch c la chn cho bo co chn lc (nhm B), ng thi nn tham kho kin t vn ca cc nh lm sng, cc dc s, Khoa chng nhim khun, Hi ng thuc v iu tr cng Khoa dc ca bnh vin. Cc bo co cn em li nhng gi tr v hiu qu trn lm sng ng thi h tr gim thiu c s pht trin ca cc chng thuc vi h bnh thng a khng thuc do s lm dng khng sinh ph rng. Kt qu bo co vi cc khng sinh trong

M100-S21 nhm B khng c trong bo co thng qui nhng lun cn c sn trong trng hp cn thit i vi mt s bnh phm. Cn bo co khi pht hin s khng thuc mi (v d, vi khun khng khng sinh thay th mc d vi khun ny nhy cm vi khng sinh u tin-hng u).

II.

Kt qu bo co Cc gi tr MIC (nng c th ca MIC) nh c m t trong bng M07-A8 c th c bo co trc tip cho bc s lm sng nhm phc v cng tc chm sc sc kho. Tuy nhin bc s lm sng cng cn phi hiu cc kt qu ny. Do cc Bc s lm sng cn c cung cp nhng thng tin v s din gi kt qu khng sinh mt cch u n. Tiu chun c kt qu v nh gi gi tr MIC i vi tng nhm vi khun c gii thiu trong ti liu CLSI-M23. Cc tiu chun c kt qu v nh gi gi tr MIC v khoanh giy khuch tn c da trn liu dng v ng dng thng thng M.

A. 1.

Din gii kt qu khng sinh nhy cm, trung gian v khng c bo co v nh ngha nh sau: Nhy cm (S) Kt qu l nhy cm khi vi khun b c ch bi nng thng thng t c ca mt khng sinh no khi dng vi liu c ch nh iu tr nhim trng.

2.

Trung gian (I) Khng trung gian (Intermediate) l kiu khng trong vi nhng nng c ch ti thiu ca mt khng sinh thng t c trong mu v t chc cho p ng thp hn so vi kiu nhy cm (S). Khng trung gian phn nh hiu qu lm sng ti cc c quan, b phn m thuc phn b (VD: nng khng sinh nhm quinolones v khng sinh nhm beta-lactam trong nc tiu) hoc kt qu iu tr t c khi s dng khng sinh vi liu cao hn liu thng thng, (VD: khng sinh nhm beta-lactam). i vi kiu khng ny cn thn trng khi nh gi ranh gii mc khng, trnh gy ra s khng thng nht trong vic nhn nh kt qu, c bit i vi cc loi thuc c gii hn c tnh hp.

3.

Khng (R) Khng (Resistant), l kiu khng m khng sinh liu thng thng khng c kh nng c ch s pht trin ca vi khun hoc c khng nh qua nng c ch v ng knh vng c ch nm trong gii hn ca c ch khng, hoc thc t khng sinh khng c hiu qu trong iu tr lm sng.

4.

Khng nhy cm (NS)

M100-S21 L mt cch din gii kt qu dng cho mt s chng vi khun ch c tiu chun c kt l nhy cm. Bi v him hoc khng c cc trng hp khng xy ra cc chng vi khun ny. Cc chng vi khun c gi tr MIC cao hn hoc c ng knh vng c ch thp hn gi tr nhy cm cn c bo co l khng nhy cm. LU 1: Mt chng cho kt qu khng nhy cm khng c ngha l chng thc s c c ch khng. iu ny c th do cc chng, c gi tr MIC ln hn gi tr nhy cm hoc thiu c ch khng. C ch khng ny c th gp phi trong nhm phn b t nhin rng sau thi im xy dng gi tr nhy cm. LU 2: i vi cc chng cho kt qu khng nhy cm, phn lp nh danh v th nghim nhy cm khng sinh cn c khng nh li (Xem Ph lc A). B. i vi mt s nhm vi khun khng c lit k trong cc bng t 2A n bng 2J, tham kho ti liu hng dn CLSI-M45- Phng Php cho Th Nghim Tnh Nhy Cm Khng Sinh bng Phng Php Pha Long v Khoanh Giy vi Vi Khun Kh Pht Trin v Vi Khun Him Gp. Ti liu ny cung cp nhng phng php chun khuyn co cho th nghim tnh nhy cm khng sinh. N bao gm cc thng tin v la chn khng sinh, din gii kt qu, kim sot cht lng. Cc nhm vi khun c cp trong ti liu ny l Abiotrophia v Granulicatella spp. (hay Streptococci thiu ht v mt dinh dng), Aeromonas hydrophilia, Bacillus spp., (tr B. anthracis), Campylobacter jejuni/coli, Corynebacterium spp., (bao gm c C. diphtheriae), Erysipelothrix rhusiopathiae, nhm HACEK: Aggregatibacter spp. (trc y l nhm Aphrophilus ca h Haemophilus (v d, H. aphrophilus, H. paraphrophilus, H. segnis) Actinobacillus actinomycetemcomitans, Cardiobacterium spp., Eikenella corrodens v Kingella spp.; Helicobacter pylori; Lactobacillus spp., Leuconostoc spp., Listeria monocytogenes, Moraxella catarrhalis, Pasteurella spp., Pediococcus spp., cc chng vi khun c th s dng trong khng b sinh hc v Vibrio spp., bao gm c Vibrio cholerae i vi cc vi khun khc khng c cp trn, cc nghin cu cha xy dng tiu chun phn tch kt qu. Cc vi khun ny c th i hi iu kin nui cy, mi trng nui cy khc hoc c s pht trin khng n nh. i vi cc vi khun ny, tham kho t vn ca cc chuyn gia v bnh truyn nhim v vic tin hnh cc th nghim tnh nhy cm khng sinh v phn tch kt qu. Trong trng hp cn thit tin hnh th nghim, phng php khng sinh pha long l thch hp nht, v c th chuyn chng n phng th nghim chun xt nghim. Cn cnh bo cho bc s lm sng nhng hn ch ca th nghim cng nh vic phn tch kt qu.

C.

M100-S21 Cn c s phi hp gia cc chuyn gia v bnh truyn nhim, cc dc s, cc chuyn gia chng nhim khun v hi ng iu tr trong vic xy dng cc chnh sch lin quan n cc th h khng sinh lu tin. a s cc trng hp, kt qu khng v trung gian khng nn phi hp trong cng mt s liu thng k. Tham kho ti liu CLSI-M39-Phn tch v trnh by s liu th nghim nhy cm khng sinh lu tin.

III.

Tho lun v liu php Mt s tho lun c a ra lin quan n nhng bn khon trong qu trnh iu tr. Nhng tho lun ny c nh du bng k hiu Rx. C th a cc tho lun ny vo bnh n hoc bo co. V d: cn a vo bo co v tnh nhy cm ca enterococcus phn lp t bnh phm mu vi nhn xt liu php phi hp khng sinh ampicillin, penicillin hoc vancomycin (i vi cc chng nhy cm) vi mt khng sinh nhm aminoglycoside thng c ch nh trong nhim khun enterococal th nng, v d nh vim ni tm mc, tr khi khng mc cao vi c gentamicin v streptomycin. Phi hp ny c tc dng hip ng tiu dit vi khun Enterococcus Liu khng sinh c ch nh thng rt khc nhau. Trong mt s trng hp, gi tr MIC da vo ch s dc ng hc hoc s dng liu lng c bit cho bnh nhn. Trong trng hp s dng liu lng c bit cho bnh nhn c t ra, nhng ch thch v liu lng phi a vo bng bo co.

IV.

Khng nh kt qu trn bnh nhn Cc thng s ca th nghim c kim sot bi qui trnh qun l cht lng khuyn co c m t trong ti liu ny. Tuy nhin, kt qu chp nhn c c t vic th nghim cc chng chun khng th m bo chc chn tuyt i cho kt qu thu c khi tin hnh th nghim vi cc chng phn lp t bnh nhn. Do cn xem xt tt c cc kt qu th nghim vi tt c cc loi khng sinh vi cc chng phn lp t bnh phm trc khi bo co. iu gip m bo: 1) Kt qu khng sinh nht qun vi kt qu nh danh vi khun; 2) kt qu ca tng khng sinh c th trong mt nhm khng sinh phi mang tnh logic th bc theo hot ph khng khun (v d: cephems th h 3 phi c tc dng mnh hn cephem th h 1 v 2 i vi Enterobacteriaceae); 3) vi khun nhy cm vi mt s loi khng sinh v cha c bo co no v s khng thuc i vi khng sinh c ghi nhn vi tiu chun c kt qu l nhy cm trong ti liu M100 (v d, vancomycin v Streptococcus spp). i vi cc trng hp kt qu bt thng hoc khng nht qun, cn kim tra li cc thng s sau: 1) li ghi chp; 2) nhim trong qu trnh th nghim (kim tra v trng); 3) i vi th nghim MIC, a mi trng khng m bo cht lng (v, mi trng khng kn a, dy khng ng tiu chun); 4) kt qu trc trn bnh nhn (v d, bnh nhn phn lp c cng loi vi khun c kt qu khng sinh bt thng trc ). Trong trng hp khng xc nh c nguyn nhn gy ra kt qu sai lch, cn tin hnh li th nghim v/hoc nh danh li tc nhn gy

M100-S21 bnh. Hoc c th thay i phng php th nghim. Tham kho ph lc A danh sch cc kt qu cn xc nh li. Mi phng xt nghim nn xy dng phng php x l cc kt qu bt thng v nhn mnh v nh hng ca cc kt qu n vic chm sc sc kho ca bnh nhn. V. S pht trin ca tnh trng khng thuc v th nghim phn lp lp li Mt s vi khun ban u nhy cm khng sinh nhng sau mt thi gian iu tr tr nn khng trung gian hoc khng thuc. Do , vic phn lp c cng mt chng gy bnh trn cng bnh nhn cng v tr ly bnh phm nn c th nghim pht hin s xut hin ca cc chng khng thuc. S khng thuc c th xy ra trong vng 3 ti 4 ngy v mt s vi khun khng thuc thng gp bao gm Enterobacter, Citrobacter, Serratia spp., khng cephalosporin th h 3; trc khun m xanh P. aeruginosa khng tt c cc loi khng sinh, t cu khng khng sinh nhm quinolones. i vi t cu vng (S. aureus), cc chng nhy cm vi vancomycin cng c th tr nn khng trung gian nu iu tr ko di. Trong mt s trng hp, th nghim pht hin cc chng khng mi c tin hnh sm hn 3-4 ngy v hin tng khng mi c th xy ra sm hn. a ra c quyt nh th nghim sm cn c s hiu bit v cc tnh hung c th v tnh trng sc kho ca bnh nhn (v d, Enterobacter cloaceae phn lp t cy mu trn bnh nhn s sinh thiu thng). Phng xt nghim hng dn thi im thc hin th nghim xc nh hin tng khng mi sau khi t vn cng cc cn b y t khc trong bnh vin. VI. Cnh bo Mt s gp c ghi trong bng. Nhng gp ny lin quan n vic hiu nhng kt qu mt cch sai lch gy nguy him c th xy ra khi mt s loi khng sinh c th nghim v bo co l nhy cm i vi mt s vi khun gy bnh. Nhng chng ny c nh du vi ch Cnh bo. Cnh bo: Cc cp khng sinh v vi khun sau y c th c tc dng trong phng xt nghim nhng khng c hiu qu iu tr trn lm sng, do khng c bo co l nhy cm V tr Bng 2A Bng 2C Vi khun Salmonella spp., Shigella spp. Staphylococcus spp., khng oxacillin Khng sinh khng c bo co l nhy cm Cephalosporin th h 1, 2, cephamycins, aminoglycoside Penicillins, phi hp khng sinh -lactam/cht c ch men -lactamase, cephems c kh nng khng staphylococcal, carbapenems Aminoglycosides (khng k nng cao), cephalosporins, clindamycin v trimethoprim-sulfamethoxazole

Bng 2D

Enterococcus spp.

M100-S21 VII. Th nghim sng lc

Th nghim sng lc, theo nh m t trong ti liu ny, xc nh mt chng l nhy cm hoc khng vi mt hoc mt s khng sinh da trn c ch khng c th hoc biu hin khng c th. Mt s th nghim sng lc c nhy v c hiu m bo. Kt qu ca th nghim sng lc ny cho kt qu ng tin cy v c th bo co m khng cn n th nghim h tr khc. Cc chng khc i hi th nghim thm khng nh kt qu thu c t th nghim sng lc. Di y l bng tng kt cc th nghim sng lc; chi tit ca tng th nghim bao gm c hiu ca th nghim, cc hn ch, v cc th nghim h tr cn c khng nh kt qu, c cung cp trong cc bng b sung c lit k di y. Chng vi khun V tr bng C ch khng hoc biu hin khng Enterobacteriaceae 2A-S1 Sinh ESBL C 2 phng php vi pha long v khoanh C, nu th nghim sng lc dng giy khuch tn vi cc khng sinh nhm tnha cephalosporin v aztreonam 2A-S2 Sinh Carbapenemase C 2 phng php vi pha long v khoanh C, nu th nghim sng lc dng giy khuch tn vi cc khng sinh nhm tnh carbapenems 2C-S3 Sinh Carbapenemase C 2 phng php vi pha long v khoanh C, nu th nghim sng lc dng giy khuch tn vi cc khng sinh nhm tnh carbapenems Staphylococcus aureus 2C-S4 Sinh beta-lactamase Test nhanh xc nh -lactamase Nu th nghim sng lc m tnh, tin hnh th nghim MIC vi penicillin v th nghim sinh beta-lactamase (nu MIC penicillin 0.12 g/ml hoc ng knh vng c ch 29 mm) trn Th nghim sng lc Th nghim h tr khng nh?

M100-S21 cc chng tip theo trn cng bnh nhn; cn nhc lm PCR xc nh gen blaZ

Khng Oxacilllin

Pha long trn thch: MHA vi 4% NaCl Khng v 6 g/ml oxacillin

C ch khng oxacillin C 2 phng php vi pha long v khoanh Khng qua trung gian mecA giy khuch tn vi cefoxitin

MIC Vancomycin 8 Pha long trn thch; BHI vi 6 g/ml C, nu th nghim sng lc cho kt g/ml vancomycin qu dng tnh

Khng clindamycin suy C 2 phng php vi pha long v khoanh Khng din giy khuch tn vi clindamycin v erythromycin Khng mupirocin mc C 2 phng php vi pha long v khoanh Khng cao T cu khng sinh men coagulase 2C-S5 Sinh beta-lactamase giy khuch tn vi mupirocin Test nhanh xc nh -lactamase Nu th nghim sng lc m tnh, tin hnh th nghim MIC vi penicillin v th nghim sinh beta-lactamase (nu MIC penicillin 0.12 g/ml hoc ng knh vng c ch 29mm) trn cc chng tip theo trn cng bnh nhn; cn nhc lm PCR xc nh gen blaZ

M100-S21 C ch khng oxacillin Khoanh giy khuch tn vi cefoxitin qua trung gian mecA Khng clindamycin suy C 2 phng php vi pha long v khoanh Khng din giy khuch tn vi clindamycin v erythromycin Enterococci 2D-S6 Khng vancomycin Pha long trn thch vi vancomycin C, nu th nghim sng lc dng tnh Khng aminiglycoside C phng php vi pha long, pha long Khng i vi MIC; c i vi khoanh trn thch v khoanh giy khuch tn vi giy, nu khng thuyt phc gentamicin v streptomycin Streptococcus pneumoniae Streptococcus spp. 2H-1-S7 Khng suy din clindamycin C 2 phng php vi pha long v Khng khoanh giy khuch tn vi clindamycin v erythromycin 2G Khng penicillin Khoanh giy khuch tn vi oxacillin C, nu khng nhy cm Khng

mc cao (HLAR)

Nhm tan mu beta

Vit tt: BHI, canh thang BHI; ESBL, khng lactam ph rng; FDA, Cc qun l Thuc v An ton Thc phm Hoa K; HLAR, khng amynoglycoside nng cao; MHA, thch Mueller-Hinton; MIC, Nng c ch ti thiu; MRSA, T cu vng khng methicilin
a

Nu s dng cc im nhy cm cephalosporin v aztreonam sa, khng cn tin hnh th nghim ESBL; nu vn tin hnh th nghim sng lc ESBL,

cn tin hnh th nghim khng nh xc nh s c mt ca ESBL.

M100-S21 VII. Cc ch vit tt AST th nghim nhy cm khng sinh ATCC tn thng mi ca h thng chng chun theo tiu chun ca Hoa K BHI Canh thang no tim BLA -lactamase dng tnh (pht hin bng th nghim chromogenic cephalosporin) BLNAR -lactamase m tnh, khng ampicillin BSC t an ton sinh hc BSL2 An ton sinh hc cp 2 BSL3 An ton sinh hc cp 3 CAMHB canh thang Mueller-Hinton iu chnh cation CDC Trung tm kim sot v phng nga dch bnh (Hoa K) CoNS T cu khng sinh men coagulase CSF dch no tu DMF dimethyl formamide DMSO dimethyl sulfoxide ESBL men -lactamase ph rng FDA Cc qun l an ton thuc v thc phm HLAR khng aminoglycoside nng cao HTM Mi trng th nghim Haemophilus KPC K. pneumonia sinh men carbapenemases LHB Ly gii mu nga MHA Thch Mueller-Hinton MHB Canh thang Mueller-Hinton MIC Nng c ch ti thiu (Nng khng sinh ti thiu c ch vi khun) MRS Staphylococci khng methicillin MRSA T cu vng khng methicillin NAD nicotinamide adenine dinucleotide PABA para-aminobenzoic axit PBP 2a Protein 2a gn penicillin QC kim sot cht lng

M100-S21 Bng 1A. Cc nhm khng sinh vi cc ch dn lm sng ca FDA cn c th nghim v bo co thng qui i vi cc vi khun d mc ti cc phng xt nghim vi sinh lm sng Hoa K NHM A. TH NGHIM V BO CO U TIN Enterobacteriaceaeg Ampicilling Pseudomonas aeruginosa Ceftazidime Staphylococcus spp. Azithromycinc hoc clarithromycinc hoc erythromycinc Clindamycinc Oxacillin ( cefoxitin)k,l Penicillink Enterococcus spp.n Ampicillin Penicillino

Cefazolinh, i

Gentamicin Tobramycin Piperacillin

Gentamicin Tobramycin

Trimethoprimsulfamethoxazole

NHM Be. TH NGHIM U TIN V BO CO CHN LC

Amikacin Amoxicillin-clavulanic axit Ampicillin-sulbactam Piperacillin-tazobactam Ticarcillin-clavulanic axit Cefuroxime

Amikacin Aztreonam Cefepime

Daptomycin Linezolid Telithromycind

Daptomycin Linezolid Quinupristindalfopristinp

Ciprofloxacin Levofloxacin Cefepime Cefotetan Cefoxitin Imipenem Meropenem Piperacillin-tazobactam Ticarcillin

Doxycycline Minocycline Tetracyclined Vancomycin Rifampinb

Vancomycin

M100-S21 Cefotaxime hoc Ceftriaxoneg,h,i Ciprofloxacing Levofloxacing Doripenem Ertapenem Imipenem Meropenem Piperacillin Trimethoprimsulfamethoxazoleg
g,h,i

NHM Cf. BO CO CHN LC B SUNG

Aztreonami Ceftazidimei

Chloramphenicolc

Gentamicin (ch dng sng lc khng mc cao)

Ciprofloxacin hoc levofloxacin hoc ofloxacin Moxifloxacin Chloramphenicol Tetracyclinea

c,g

Streptomycin (ch dng sng lc khng mc cao)

Gentamicin Quinupristin-dalfopristinm

M100-S21 NHM U. B SUNG CHO BNH PHM NC TIU Cephalothin

f

Lomefloxacin hoc Ofloxacin Lomefloxacin hoc ofloxacin Norfloxacin Nitrofurantoin Sulfisoxazole Trimethoprim

Lomefloxacin Norfloxacin

Ciprofloxacin Levofloxacin Norfloxacin Nitrofurantoin

Norfloxacin

Nitrofurantoin Sulfisoxazole Trimethoprim Tetracyclinea

Ch th nghim nng c ch ti thiu MIC, th nghim khoanh giy khuch tn khng ng tin cy

M100-S21 Bng 1A (Tip) Acinetobacter spp. j NHM A. TH NGHIM V BO CO U TIN Burkholderia cepacia j Stenotrophomonas maltophilia j,k Trimethoprimsulfamethoxazole Cc chng khc khng thuc nhm Enterobacteriaceaej Ceftazidime
*

Ampicillin-sulbactam Ceftazidime Ciprofloxacin Levofloxacin Imipenem Meropenem Gentamicin Tobramycin Amikacin

Trimethoprimsulfamethoxazole

Gentamicin Tobramycin Piperacillin

NHM Be. TH NGHIM U TIN BO CO CHN LC

Ceftazidime
* *

* c *

Ceftazidime Chloramphenicol
c

Amikacin Aztreonam Cefepime Ciprofloxacin Levofloxacin Imipenem Meropenem Piperacillin-tazobactam Ticarcillin-clavulanate Trimethoprimsulfamethoxazole

Chloramphenicol Levofloxacin

Levofloxacin Minocycline
*

Piperacillin-tazobactam Ticarcillin-clavulanic axit

Meropenem Minocycline * Ticarcillin-clavulanate

Ticarcillin-clavulanate

Cefepime

Cefotaxime Ceftriaxone

M100-S21 Doxycycline Minocycline Tetracycline Piperacillin Trimethoprimsulfamethoxazole

NHM Cf. BO CO CHN LC B SUNG

Cefotaxime Ceftriaxone

Chloramphenicolc

NHM U. B SUNG CHO BNH PHM NC TIU

Lomefloxacin hoc oloxacin Norfloxacin Sulfisoxazole Tetracyclinea

=Ch th nghim nng c ch ti thiu MIC, th nghim khoanh giy khuch tn khng ng tin cy

M100-S21 Bng 1A. (Tip) Cnh bo: Cc khng sinh sau y c cp trong ti liu ny khng nn bo co thng qui vi cc chng vi khun phn lp t dch no ty. Cc khng sinh ny khng phi l cc thuc c la chn v c th khng c hiu qu trong iu tr nhim khun dch no ty do cc chng vi khun ny gy ra (v d: cc chng vi khun trong bng 2A n 2J: Cc khng sinh ch dng ng ung Cc khng sinh Cephalosporin th h 1 v 2 (tr Cefuroxime ng tim) v cephamycins Clindamycin Macrolides Tetracycline Fluoroquinolones

LU 1:

Vic la chn cc loi khng sinh thch hp nht cho th nghim v bo co nhy cm khng sinh i vi cc bnh nhim khun do cc phng xt nghim lm sng trc tip tho lun vi khoa dc, Hi ng Thuc v iu tr v khoa chng nhim khun quyt nh. Cc bng trn bao gm cc vi khun cng vi cc khng sinh i kem c chng minh hiu qu bng cc th nghim in vitro. Cc nhm A, B, C v U gm danh sch mt s loi khng sinh c la chn cho th nghim tnh nhy cm khng sinh i vi tng nhm vi khun. S la chn ny da trn hiu qu lm sng, tnh trng khng khng sinh ca vi khun vi khng sinh, v gim thiu s pht trin ca tnh trng khng khng sinh, gi thnh, ch nh lm sng ca FDA, cng nh da vo nhng hng dn mi nht ca cc khng sinh trong bng thuc khng sinh u tin v thuc khng sinh thay th, ngoi ra c cc gi c th trong phn ghi ch e v f.Khng khng sinh mi (khng khng sinh khng mong mun) phi c bo co (Enterobacteriaceae vi nhm carbapenem) Th nghim i vi cc loi thuc khng sinh chn lc c th s dng cho mc ch chng nhim khun.

LU 2:

Danh sch khng sinh trong tng bng c lit k theo nhm c kt qu th nghim tnh nhy cm (nhy cm, trung gian, khng) v hiu qu trn lm sng tng t. Do , ch la chn i din mt thuc trong mi nhm cho vic th nghim. Trong mi bng, ch hoc c dng ch cc nhm khng sinh cho kt qu khng r rng v s khng thuc hoc tnh nhy cm. C ngha l cc li ln khng qu 3% v

M100-S21 cc li nh khng qa 10% tng s th nghim. Ngoi ra, dng ch hoc, khi th nghim t nht 100 chng th c trn 95% chng khng. Hoc cng c dng ch cc khng sinh c tc dng tng ng, c th la chn thay th trong khi la chn cho th nghim (v d cefotaxime hoc ceftriaxone dng cho Haemophilis influenzae). C th da trn kt qa th nghim i vi mt khng sinh suy ra kt qu i vi khng sinh cn li (v d, vi khun ng rut khng sinh ESBL nhy cm vi cefotaxime c th suy ra cng nhy cm vi ceftriaxone). Cc khng sinh c la chn bo co, phi l cc khng sinh c th nghim, tr khi c th suy lun kt qu t mt th nghim khc chnh xc hn (v d, tnh nhy cm ca staphylococci i vi oxacillin da trn th nghim vi cefoxitin) v nn ph hp vi bo co ca bnh vin. Cc trng hp khng mi cn phi c bo co (v d, Enterobacteriaceae khng carbapenems). LU 3: Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc .

Ghi ch Lu chung: a. Mt s chng nhy vi tetracycline cng c th coi l nhy vi doxycycline v micocycline. Tuy nhin, mt s chngm khng trung gian hoc khng tetracycline c th vn cn nhy cm vi doxycycline v/hoc minocycline. b. Rx: Rifampin khng nn s dng n c trong iu tr cc bnh nhim khun. c. Khng bo co thng qui vi cc chng phn lp t ng tit niu d. Cc khng sinh nhm B c th tin hnh th nghim u tin nhng khi bo co ch nn chn lc khng sinh da trn cc tiu ch sau : vi khun khng khng sinh cng nhm trong nhm A. Cc ch tiu khc cho bo co c th bao gm ngun gc bnh (v d, cephalosporin th h 3 i vi trc khun gy bnh ng rut phn lp t dch no tu hoctrimethoprim-sulfamethoxazole cho cc vi khun gy vim ng tit niu), cc trng hp d ng hoc qu mn hay khng p ng vi khng sinh nhm A, bi nhim, nhim a nhiu v tr, hoccho mc ch chng nhim trng v h tr cng tc dch t. e. Nhm C bao gm cc khng sinh thay th hoc b sung c th yu cu th nghim ti cc bnh vin m ang hng chu nhng v dch gy ra bi cc vi khun khng li vi nhiu nhm khng sinh u tin hng u (c bit l cc khng sinh cng nhm, v d -lactams), i vi bnh nhn b d ng vi cc khng sinh u tin (hng u), hoc i vi iu tr cc vi khun c bit (v d, chloramphenicol i vi Salmonella spp., phn lp ngoi rut) hoc cho mc ch chng nhim trng v h tr cng tc dch t.

M100-S21 Enterobacteriaceae f. Tiu chun c kt qu Cephalothin c th c s dng d on kt qu i vi cc khng sinh cefadroxil, cefpodoxime, cephalexin v loracarbef ng ung. Cc d liu c gi rng cc kt qu ca cephalothin c th d on tnh nhy cm vi mt s cephalosporin khc vn c th ng, nhng khng c cc d liu mi y khng nh iu ny. g. Cc chng Salmonella v Shigella spp., phn lp t phn ch kt qu th nghim vi ampicillin, quinolone v trimethoprim-sulfamethoxazole nn c bo co thng qui. Ngoi ra, cephalosporin th h 3 nn c th nghim v bo co i vi Salmonella spp. phn lp ngoi rut, chloramphenicol c th th nghim v bo co nu c yu cu. h. Cefotaxime v ceftriaxone nn c th nghim v bo co i vi cc vi khun phn lp t dch no ty thay cho cephalothin v cefazolin. i. Theo nhng thng tin mi v c tnhdc ng hc (PK-PD) v hn ch lm sng, cc tiu chun c kt qu mi i vi cephalosporins (cefazolin, cefotaxime, ceftazidime, ceftizoxime v ceftriaxone) v aztreonam c xy dng v lit k trong Bng 2. Cc tiu chun c kt qu cho Cefepime v cefuroxime (khng dng cho ng ung) cng c xc nh nhng khng c s thay i ln no v c trnh by Bng 2A. Khi s dng cc tiu chun mi, khng cn th nghim ESBL mt cch thng quy trc khi bo co kt qu (v d, khng cn thay i cc kt qu i vi cephalosporins, aztreonam, hoc penicillin t nhy cm sang khng). Tuy nhin, cho n khi cc phng xt nghim thc hin tin hnh theo cc tiu chun c kt qu mi, th nghim ESBL nn tin hnh nh m t trong Bng 2A-S1. Th nghim ESBL c th vn c ngha i vi dch t hc hoc mc ch chng nhim khun. Lu rng, cc tiu chun c kt qu i vi cc thuc khng sn c nhiu nc (v d, moxalactam, cefonicid, cefamandole, v cefoperazone) khng c nh gi. Nu xem xt s dng cc thuc ny cho E. Coli, Klebsiella, hoc Proteus spp., nn tin hnh th nghim ESBL (xem Bng 2AS1). Nu cc chng cho kt qu th nghim ESBL dng tnh, cc kt qu i vi moxalactam, cefonicid, cefamandole v cefoperazone nn bo co l khng. Pseudomonas aeruginosa v cc vi khun khc khng thuc h Enterobacteriaceae j. Cc vi khun khng thuc h Enterobacteriaceae bao gm Pseudomonas spp. V cc trc khun Gram m, khng ln men glucose, d mc tr P. aeruginosa, Acinetobacter spp., Burkholderia cepacia, B. mallei, B. pseudomallei v Stenotrophomonas maltophilia bi v c cc danh sch ring i vi cc thuc c gi th nghim v bo co i vi cc chng ny.

M100-S21 xut th nghim v bo co i vi B. mallei v B. pseudomallei trong ti liu CLSI M45.

Staphylococcus spp. k. Cc chng t cu nhy cm vi penicillin th cng nhy cm vi cc sinh khc cng nhm; cc phi hp -lactam/c ch -lactamase, cc khng sinh cephems, v carbapenems c FDA thng qua trong iu tr nhim t cu. Cc chng khng Penicillin, nhy cm vi oxacillin th thng khng vi cc penicillin d b phn hu bi men penicillinase, nhng nhy cm vi cc penicillin n nh vi penicilinase, cc phi hp khng sinh -lactam/cht c ch -lactamase, cephems c hot tnh khng staphylococcal thch hp v carbapenems. Staphylococci khng oxacillin th cng khng vi tt c cc khng sinh nhm beta-lactam hin nay tr cc cephalosporin th h mi vi hot tnh chng MRSA. Do , tnh nhy cm hoc tnh khng vi cc khng sinh thuc nhm beta-lactam c th c suy lun t kt qu ca th nghim vi penicillin v hoc cefoxintin hoc oxacillin. Th nghim thng qui vi cc khng sinh penicillin khc, cc phi hp khng sinh -lactam/cht c ch -lactamase, cc khng sinh nhm cephem, hoc cc khng sinh nhm carbapenem khng c khuyn dng. l. Kt qu ca th nghim khoanh giy khng sinh khuch tn v/hoc MIC vi cefoxitin c th dng d on tnh trng khng oxacillin qua trung gian mecA cc chng S. aureus, S. lugdunensis. Vi cc staphylococci khng sinh coagulase (ngoi tr S. Lugdunensis) s dng khoanh giy cefoxitin l phng php tt nht pht hin khng oxacillin qua trung gian mecA. . Cefoxitin c th c s dng lm i din pht hin khng oxacillin; bo co kt qu l nhy cm hay khng vi oxacillin da trn kt qu ca cefoxitin.. Nu mt khng sinh thuc nhm penicillin bn vi men penicillinase c th nghim, th oxacillin l khng sinh c la chn dng v kt qu c th c p dng cho cc khng sinh penicillin bn vi men penicillinase khc nh cloxacillin, dicloxacillin v flucloxacillin. m. Cc bo co i lp v cc chng Staphylococcus aureus nhy cm vi methicillin. Enterococcus spp. n. Cnh bo: i vi Enterococcus spp., cephalosporin, aminoglycoside (tr th nghim sng lc khng mc cao), clindamycin v trimethoprim-

sulfamethoxazole c th cho hiu qu trn in vitro nhng khng c hiu qu trn lm sng, v cc chng vi khun thng khng c bo co cc kt qu nhy cm. o. Enterococci nhy cm vi penicillin th cng nhy cm vi ampicillin, amoxicillin, ampicillin-sulbactam, amoxicillin-clavulanate, piperacillin-

tazobactam i vi cc chng Enterococci khng sinh men -lactamase. Tuy nhin, Enterococci nhy cm vi ampicillin khng th suy lun l nhy cm

M100-S21 vi penicillin. Nu cn thit, phi tin hnh th nghim mc nhy cm vi penicillin. Rx: S phi hp ampicillin, penicillin, hoc vancomycin (i vi cc chng nhy cm), vi aminoglycoside, thng c ch nh trong trng hp nhim enterococcal nng, v d vim mng trong tim, tr trng hp khng mc cao vi c gentamicin v streptomycin, s phi hp ny c hiu qu trong iu tr nhim Enterococcus. p. Cc bo co i lp v chng Enterococcus faecium khng vancomycin.

M100-S21 Bng 1B. Cc nhm khng sinh vi ch dn lm sng ca FDA cn th nghim v bo co thng qui i vi cc vi khun kh nui cy c thc hin ticc phng xt nghim vi sinh lm sng Hoa K. NHM A. TH NGHIM V BO CO U TIN Haemophilus spp. f Neisseria gonorrhoeae i Streptococcus pneumoniae j Erythromycina,e Penicillink (khoanh khng sinh oxacillin) Trimethoprimsulfamethoxazole Trimethoprimsulfamethoxazole Streptococcus spp. Nhm tan mu betaq Clindamycine,p Erythromycina,e,p Penicillinn hoc Ampicillinn Streptococcus spp. nhm Viridansr
* *

Ampicillin f,h

Ampicillinm Penicillinm

NHM Bb. TH NGHIM U TIN BO CO CHN LC

Ampicillin-sulbactam

* *

Cefepime Cefotaximek * Ceftriaxonek Clindamycine

Cefepime hoc Cefotaxime Ceftriaxone

Cefepime Cefotaxime Ceftriaxone

Cefuroxime (ng tim)

Cefotaximef hoc ceftazidime hoc ceftriaxonef

Gemifloxacink Levofloxacink Moxifloxacink Ofloxacin

Vancomycin

Vancomycin

M100-S21
*

Meropenem

Telithromycin Chloramphenicole,f Tetracyclined

Meropenemf, Vancomycink

Azithromycing Clarithromycing NHM Cc. BO CO CHN LC B SUNG Aztreonam

Cefixime hoc cefpodoxime

Amoxicillin * Amoxicillin-clavulanic axit

Chloramphenicole

Chloramphenicole

Clindamycine Erythromycina,e
*

Amoxicillin-clavulanic axitg Cefotaxime hoc ceftriaxone Cefaclorg Cefprozilg Cefdinirg hoc cefiximeg hoc Cefpodoxime g Cefuroxime (ng ung)g Ciprofloxacin hoc ofloxacin Chloramphenicole Cefoxitin Cefuroxime Cefuroxime
*

Daptomycin

Levofloxacin Ofloxacin Linezolid Linezolid

M100-S21 Quinupristindalfopristino Ciprofloxacin hoc levofloxacin hoc lomefloxacin hoc moxifloxacin hoc Ofloxacin Penicillini
* *

Ertapenem Imipenem

Linezolid

Gemifloxacin Ertapenem hoc imipenem Rifampin Telithromycing Tetracyclined

*

Spectinomycin Tetracyclined

Rifampinl

Ch th nghim nng c ch ti thiu MIC, th nghim khoanh giy khuch tn khng ng tin cy.

Th nghim thng qui l khng cn thit (xem ghi ch n)

M100-S21 Bng 1B. (Tip) Cnh bo: Cc khng sinh sau y c cp trong ti liu ny khng nn bo co thng qui vi cc chng vi khun phn lp t Dch no ty . Cc khng sinh ny khng phi l cc thuc c la chn v c th khng c hiu qu trong iu tr nhim khun Dch no ty do cc chng vi khun ny gy ra (v d: cc chng vi khun trong bng 2A n 2J: Cc khng sinh ch dng ng ung Cc khng sinh Cephalosporin th h 1 v 2 (tr Cefuroxime ng tim) v cephamycins Clindamycin Macrolides Tetracycline Fluoroquinolones Tetracycline Fluoroquinolones

LU 1:

Vic la chn cc loi khng sinh thch hp nht cho th nghim nhy cm khng sinh i vi cc bnh nhim khun do cc phng xt nghim lm sng trc tip lm vic kt hp vi khoa dc, Hi ng Thuc v iu tr v Hi ng - Gim st nhim khun quyt nh. Cc nhm A, B, C v U gii thiu danh sch mt s loi khng sinh c la chn cho th nghim tnh nhy cm khng sinh i vi tng nhm vi khun. i vi tng th nghim c th, c th iu chnh vic la chn khng sinh cho hp l da trn hiu qu lm sng, tnh khng ph bin, gim thiu mc khng, gim chi ph, cc ch s lm sng ca FDA v vic s dng khng sinh, nhng hng dn mi nht v cc nhm thuc la chn hng u v nhm thuc thay th, ngoi ra c cc gi c th trong phn ghi ch b v c. Th nghim i vi cc loi thuc khng sinh chn lc c th s dng cho mc ch chng nhim khun.

LU 2:

Danh sch khng sinh trong tng bng c lit k theo nhm c kt qu th nghim tnh nhy cm (nhy cm, trung gian, khng) v hiu qu trn lm sng tng t. Do , ch la chn i din mt thuc trong mi nhm cho vic th nghim. Trong mi bng, ch hoc c dng ch cc nhm khng sinh cho kt qu khng r rng v s khng thuc hoc tnh nhy cm. C ngha l cc li ln khng qu 3% v

M100-S21 cc li nh khng qa 10% tng s th nghim. Ngoi ra, dng ch hoc, khi th nghim t nht 100 chng th c trn 95% chng khng. Hoc cng c dng ch cc khng sinh c tc dng tng ng, c th la chn thay th trong khi la chn cho th nghim (v d cefotaxime hoc ceftriaxone dng cho Haemophilis influenzae). C th da trn kt qa th nghim i vi mt khng sinh suy ra kt qu i vi khng sinh cn li. V d, vi khun ng rut khng sinh ESBL nhy cm vi cefotaxime c th suy ra cng nhy cm vi ceftriaxone. Cc kt qu thu c t th nghim vi cefotaxime s c bo co trong bo co s bao gm c lu v tnh nhy cm ca chng vi ceftriaxone. Khi khng c hoc gia cc khng sinh trong bng, th nghim mt khng sinh khng th c s dng d on kt qu ca khng sinh cn li hoc kt qu khc nhau hoc s liu khng y . LU 3: Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc . Ghi ch Lu chung: a. C th da trn kt qu th nghim erythromycin suy ra mc nhy cm v khng vi azithromycin, clarithromycin, v dirithromycin. b. Cc khng sinh nhm B c th tin hnh th nghim c lp nhng khi bo co ch nn chn lc khng sinh i din, i vi cc vi khun khng khng sinh cng nhm trong nhm A. Cc ch tiu khc cho bo co c th bao gm ngun gc bnh phm chn lc (v d, cephalosporin th h 3 i vi Haemophilus influenzae phn lp t dch no tu hoc TMX cho cc vi khun gy vim ng tit niu), cc trng hp d ng hoc qu mn hay khng p ng vi khng sinh nhm A, bi nhim, nhim a v tr vi nhiu loi vi khun, hoc bo co cho mc ch chng nhim trng v h tr cng tc dch t. c. Nhm C gm cc khng sinh i din, thay th hoc b sung c th yu cu th nghim cc vi khun khng trong vng nguy c v mt dch t hc i vi mt s khng sinh c bn (c bit l cc khng sinh cng nhm, v d -lactams), hoc i vi iu tr cc vi khun c bit (v d, chloramphenicol i vi Salmonella spp., phn lp ngoi rut) hoc bo co cho mc ch chng nhim trng v h tr cng tc dch t. d. Cc vi khun nhy cm vi tetracycline th cng nhy cm vi doxycycline v minocycline. e. Khng bo co thng qui cc chng phn lp t ng tit niu Haemophilus spp. f. Ch cc kt qu th nghim vi ampicillin, mt trong s cc khng sinh cephalosporin th h 3, chloramphenicol, v meropenem nn c bo co thng qui i vi H. influenzae phn lp t Dch no ty.

M100-S21 g. Amoxicillin-axit clavulanic, azithromycine, clarithromycin, cefaclor, cefprozil, loracarbef, cefdinir, cefixime, cefpodoxime, cefuroxime and telithromycin l cc khng sinh ng ung c th c dng theo kinh nghim trong iu tr nhim khun h hp do Heamophilus spp. Kt qu th nghim nhy cm khng sinh i vi cc loi khng sinh ny thng t c ngha s dng trong iu tr. Tuy nhin, nhng kt qu ny c th s dng trong cc nghin cu dch t. h. Kt qu nhy cm vi ampicillin c th c dng d on tnh nhy cm vi amoxicillin. Phn ln cc chng H. Influenza khng ampicillin v amoxicillin c kh nng sinh men -lactamase kiu TEM. Phn ln cc trng hp, th nghim -lactamase trc tip c th pht hin nhanh mc khng ampicillin v amoxicillin. Neiseria gonorrhoeae i. Th nghim -lactamase s pht hin chng N.gonorrhoeae khng penicillin v cng c th c s dng trong nghin cu dch t hc. Cc chng khng qua trung gian chromosome c th pht hin bng k thut khoanh giy khuch tn hoc khng sinh pha long MIC. Streptococcus pneumoniae j. Cc chng S. pneumoniae nhy cm vi levofloxacin th c th suy ra nhy cm vi gemifloxacin v moxifloxacin. Tuy nhin, S. pneumoniae nhy cm vi gemifloxacin hoc moxifloxacin khng th suy ra nhy cm vi levofloxacin. k. Penicillin v cefotaxime hoc ceftriaxone hoc meropenem nn c th nghim bng phng php MIC ng cy (v d nh m t trong ti liu CLSI M07-A8) v c bo co thng qui vi cc chng S. pneumoniae phn lp t dch no ty. Cc chng ny nn c th nghim vi vancomycin bng phng php MIC hoc khoanh giy khuch tn. Vi cc chng phn lp t cc v tr khc, c th dng th nghim sng lc bng khoanh giy oxacillin. Nu vng c ch ca oxacillin c ng knh 19mm, cn th nghim khng nh MIC ca mt trong s cc khng sinh nh penicillin hoc cefotaxime hoc ceftriaxone hoc meropenems. l. Rx: Khng nn ch nh Rifampin n c trong iu tr. Streptococcus spp. m. Rx: Cc chng khng trung gian vi penicillin hoc ampicillin c th cn liu php kt hp vi mt khng sinh nhm aminoglycoside c tc dng khng khun. n. Penicillin v ampicillin l thuc c la chn iu tr cc trng hp nhim lin cu tan mu beta. Th nghim nhy cm khng sinh i vi penicillin v cc khng sinh nhm -lactam khc c ph duyt bi FDA trong iu tr nhim lin cu tan mu beta khng cn tin hnh thng qui v

M100-S21 cc chng khng rt him gp trong nhm lin cu tan mu beta (penicillin MIC > 0.12 v ampicillin MIC > 0.25 g/ml v cha c bo co ghi nhn i vi Streptococcus pyogenes. Cc chng pht hin khng nhy cm cn tin hnh nh danh li, lp li th nghim hoc gi ti phng xt nghim chun thc khng nh kt qu (Tham kho Ph lc A). o. Cc bo co tnh khng ca S. pyogenes p. Rx: Hai khng sinh c xut cho d phng nhim Streptococci nhm B l penicillin v ampicillin. Cefazolin c s dng i vi bnh nhn n d ng vi penicillin, trong trng hp bnh nhn n qu mn mc cao, la chn clindamycin hoc erythromycin. Streptococci nhm B nhy cm vi ampicillin, penicillin v cefazolin, nhng c th khng vi clindamycin v/hoc erythromycin. i vi ph n c thai nhim Streptococci nhm B, qu mn vi penicillin th khng sinh clindamycin v erythromycin cn c th nghim v bo co. q. i vi bng ny, cc vi khun tan mu beta bao gm cc chng sinh m vi hnh thi khun lc ln nh Streptococci nhm A (S. pyogenes), C hoc G v cc chng vi khng nguyn nhm B (S. agalactiae). Cc chng vi hnh thi khun lc nh c xem l mt phn ca nhm viridans, do d nn s dng tiu chun c kt qu i vi nhm viridans.

M100-S21 Bng 1C. Cc khng sinh nn c th nghim v bo co i vi cc vi khun k kh Nhm Bacteroides fragilis v cc vi khun Gram m k kh khc Amoxicillin-clavulanic acid Ampilicillin-sulbactam Piperacillin-tazobactam TH NGHIM v BO CO U TIN Ticarcillin-clavulanic acid Gram dng k kh Ampilicillina Penicillina Amoxicillin-clavulanic acid Ampilicillin-sulbactam Piperacillin-tazobactam Ticarcillin-clavulanic acid Clindamycin

NHM A

Ertapenem Imipenem Meropenem Metronidazole

Clindamycin

Ertapenem Imipenem Meropenem Metronidazole

CHN LC B

Penicillina Ampilicillina XUNG Ceftizoxime Ceftriaxone Chloramphenicol

Ceftizoxime Ceftriaxone Cefotetam Cefocitin

BO CO

NHM C

M100-S21 Cefotetam Cefocitin Piperacillin Ticarcillin Tetracyclineb Moxifloxacin Piperacillin Moxifloxacin

Bng 1C. (Tip) LU 1: Thng tin in m l mi hoc c hiu chnh so vi phin bn trc LU 2: Phn ln cc nhim khun k kh l s bi nhim nhiu loi vi khun gm cc chng betalactamase dng tnh (c xc nh bng th nghim cephalosporin nhim sc th) v cc chng m tnh vi betalactamase nhng c kh nng khng khng sinh. Vi nhng ca nhim trng gy ra bi duy nht mt chng lactamase m tnh, penicillin hoc ampicillin l khng sinh ph hp th nghim v bo co. LU 3: Phn ln cc vi khun k kh Gram dng c phn lp t cc trng hp bi nhim nhiu vi khun khng khng sinh; tuy nhin, mt vi loi ca Clostridium spp (C. perfringens, C. septicum, C. sordellii) l cn nguyn n c ca tnh trng nhim trng. Trong trng hp ny, cc chng in hnh nhy cm vi penicillin v ampicillin. Hai khng sinh trn cn phi c th nghim v bo co. LU 4: Cc khng sinh xp cng mt l thuc cng mt nhm. Do , din gii kt qu khng sinh (nhy, trung gian, khng) v hiu qu lm sng l tng t nhau. Do , ch cn chn mt trong cc khng sinh th nghim v bo co. a. Nu -lactamase dng tnh, bo co l khng vi penicillin v ampicillin. Cn nh rng mt s chng -lactamase m tnh nhng thc cht vn khng vi nhm -lactama bi nhng c ch khc.. b. Khng phi mi thng tin u y cho vic ct ngha khng -lactama c cp trn (v d, im nhy cm [Bng 2J] v gi tr ca kim sot cht lng [Bng 4D v 4E]. Nhng thng tin chc chn s c b sung sm nht c th. Vic tin hnh th nghim c th l hu dng cho vic tch l cc thng tin v mc ch nghin cu. c. Rt nhiu trc khun Gram dng k kh khng sinh nh bo khng vi metronidazole..

M100-S21 Bng 2A. Tiu chun c kt qu ng knh vng c ch v nng c ch ti thiu (MIC) i vi Enterobacteriaceae iu kin th nghim Mi trng: Khoanh giy khuch tn: MHA Canh thang pha long: CAMHB Thch pha long: MHA Phng php tng sinh hoc trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352oC, hiu kh, Khoanh giy khuch tn: 16-18h Phng php pha long: 16-20h Cc yu cu kim sot cht lng ti thiu (Xem bng 3A v bng 4A v gii hn QC cho php) Escherichia coli ATCC* 25922 Escherichia coli ATCC* 35218 (dng cho phi hp -lactam/c ch men -lactamase)

Huyn dch vi khun:

iu kin nui cy:

*ATTC l nhn hiu thng mi c ng k cho H thng chng chun theo tiu chun Hoa K Lu chung (1) Khoa giy khuch tn: o ng knh vng c ch ( bng mt thng), bao gm ng knh khoanh giy. Soi a trn nn en vi nh sng xuyn qua. Ranh gii vng c ch xc nh bng mt vng khng c bt k khun lc no c th pht hin bng mt thng, b qua cc khun lc li ti mp m ch c th pht hin di knh hin vi. Cc chng Proteus spp., c th pht trin lan vo vng c ch i vi tng loi khng sinh nht nh. i vi chng Proteus spp., b qua s pht trin yu trong trng hp vng v khun khng r rng. i vi trimethoprim v sulfonamides, cht i khng trong mi trng c th cho php vi khun pht trin yu, do , nu vi khun pht trin mc khong 20% hoc t hn th c th khng quan tm v o ng knh vng c ch ranh gii r rng nht. i vi cc chng Salmonella v Shigella spp., c phn lp t phn, ch tin hnh th nghim v bo co thng qui i vi ampicillin, mt khng sinh nhm quinolon v/ mt khng sinh nhm fluoroquinolone, v trimethoprim-sulfamethoxazole. Ngoi ra, cephalosporin th h 3 phi c th nghim v bo co i vi Salmonella spp. phn lp t ng tiu ho v chloramphenicol c th th nghim v bo co nu yu cu im nhy cm-gii hn (breakpoint) trong cc bng i y da trn hm lng khng sinh t do trong huyt tng ngi (c chc nng gan v thn bnh thng). Khi mt im nhy cm mi c b sung, khoa xt nghim phi chia s nhng thng tin ny ti cc Bc s chuyn khoa truyn nhim, cc dc s, Hi ng thuc v iu tr, v Khoa chng nhim khun. Thng tin v k n cn phi c sot xt li v cc nh lm sng phi tin hnh hi chn xc nh liu lng iu tr cho bnh nhn nhim trng c bit.. Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc .

(2)

(3)

LU :

M100-S21 Bng 2A. (Tip) Nhm th Khng sinh nghim/ bo co PENICILLINS A Ampicillin Hm lng Gii hn ng knh vng c ch (mm) S I R 17 14-16 13 Gii hn nng c ch ti thiu (g/mL) S I R 8 16 32 Lu

10 g

(4) i din i vi ampicillin v amoxicillin. Xem lu (2). (5) Ch s dng i vi E. coli phn lp t ng tit niu.

B O

Piperacillin Mecillinam

100 g 10 g

21 15

18-20 12-14

17 11

16 8

32-64 16

128 32

O Carbenicillin 100 g 23 20-22 19 16 32 64 O Mezlocillin 75 g 21 18-20 17 16 32-64 128 O Ticarcillin 75 g 20 15-19 14 16 32-64 128 PHI HP -LACTAM/ CHT C CH -LACTAMASE B 20/10 g 16/8 32/16 Amoxicillin-clavulanic 18 14-17 13 8/4 B 16/8 32/16 axit Ampicillin-sulbactam 10/10 g 8/4 15 12-14 11 B 100/10 g 128/4 Piperacillin-tazobactam 21 18-20 17 16/4 32/4-64/4 B 128/2 Ticarcillin-clavulanic axit 75/10 g 20 15-19 14 16/2 32/2-64/2 CEPHEMS (NG TIM) (Bao gm cephalosporin th h I, II, III v IV. Tham kho Bng ch thch I.) (6) CNH BO: i vi Salmonella spp., v Shigella spp., cephalosporin th h 1 v 2 v cephamycins c th c tc dng in vitro, nhng khng c hiu qu trn lm sng, do khng c bo co v s nhy cm. (7) Theo cc nh gi mi v cc c tnh dc l-dc ng hc (PK-PD) v cc d liu lm sng gii hn, cc tiu chun c kt qu mi ( sa) i vi cc khng sinh nhm cephalosporins (cefotaxime, ceftazidime, ceftizoxime v ceftriaxone) v aztreonam ln u tin c cng b trong phin bn M100-S20 thng 1 nm 2010 v c lit k trong bng ny. Tiu chn nh gi Cefazolin cng c xem xt li vo thng 6 nm 2010 v c lit k trong bng di. Cefepime v cefuroxime (ng tim) cng c nh gi, tuy nhin, khng c s thay i cc tiu chun c kt qu i vi cc liu dng c ch nh di y. Khi s dng cc tiu chun mi, khng cn th nghim ESBL thng qui trc khi bo co (v d, khng cn thay i cc kt qu i vi cephalosporins, aztreonam, hoc penicillin t nhy cm sang khng). Tuy nhin, cho n khi cc phng xt nghim thc hin cc tiu chun mi, th nghim ESBL nn tin hnh nh m t trong Bng 2A-S1. Th nghim ESBL c th vn c ngha i vi dch t hc hoc mc ch chng nhim khun. Lu rng, cc tiu chun c kt qu i vi cc thuc khng sn c nhiu nc (v d, moxalactam, cefonicid, cefamandole, v cefoperazone) khng c nh gi. Nu xem xt s dng cc thuc ny cho E. Coli, Klebsiella, hoc Proteus spp., nn tin hnh th nghim ESBL (xem Bng 2A-S1). Nu cc chng cho kt qu th nghim ESBL dng tnh, cc kt qu i vi moxalactam, cefonicid, cefamandole v cefoperazone nn bo co l khng.

M100-S21 (8) Cc chng Enterobacter, Citrobacter v Seratia c th tr nn khng khng sinh sau qu trnh iu tr ko di vi khng sinh nhm cephalosporin th h ba. Do , cc chng ny ban u c th nhy cm, nhng sau c th tr nn khng thuc sau 3-4 ngy iu tr. Nn tin hnh th nghim lp li vi cc chng ny. A Cefazolin 30 g 23 20-22 19 2 4 8 (9) Tiu chun c kt da trn liu lng 2g mi 8 gii. Xem lu (7) (10) Tiu chun c kt qu cephalothin ch nn s dng d on kt qu i vi cc khng sinh ng ung, cefadroxil, cefpodoxime, cephalexin, v loracarbef. Cc d liu c ch ra rng cc kt qu cephalothin c th d on tnh nhy cm vi mt s khng sinh nhm cephalosporins khc c th vn chnh xc nhng khng c s liu mi y khng nh iu ny. (11) Tiu chun c kt qu da trn liu iu tr 1 g mi 8 h hoc 2 g mi 12 h. Xem lu (7). (12) Tiu chun c kt qu da trn liu iu tr 1 g mi 24 h i vi ceftriaxone v 1 g mi 8 h i vi cefotaxime. Xem lu (7).

Cephalothin

30 g

18

15-17

14

16

32

Cefepime

30 g

18

15-17

14

16

32

B B

Cefotaxime hoc ceftriaxone

30 g 30 g

26 23 16 18 18

23-25 20-22

22 19

1 1

2 2

4 4

B B B

Cefotetan Cefoxitin Cefuroxime (tim)

30 g 30 g 30 g

13-15 15-17 15-17

12 14 14

16 8 8

32 16 16

64 32 32

(13) Cc tiu chun c kt qu c da trn liu dng 1,5g mi 8h. Xem lu (7)

Ceftazidime

30 g 21

18-20 17

16

M100-S21 (14) Cc tiu chun c kt qu c da trn liu dng 1g mi 8h. Xem lu (7)

O O O O O

Cefamandole Cefmetazole Cefonicid Cefoperazone Ceftizoxime

30 g 30 g 30 g 75 g 30 g

18 16 18 21 25

15-17 13-15 15-17 16-20 22-24

14 12 14 15 21

8 16 8 8 1

16 32 16 32 2

32 64 32 64 4

Xem lu (7)

Xem lu (7) Xem lu (7) (15) Cc tiu chun c kt qu c da trn liu dng 1g mi 12h. Xem lu (7).

O Moxalactam CEPHEMS (NG UNG) B Cefuroxime (ung) O Loracarbef

30 g 30 g 30 g

23 23 18

15-22 1522 1517

14 14 14

8 4 8

16-32 816 16

64 32 32

Xem lu (7).

(16) Bi v cc chng Citrobacter, Providencia, v Enterobacter spp. c bo co cho kt qu nhy cm gi vi cefdinir v loracarbef, cc chng ny khng nn th nghim v bo co kt qu nhy cm bng phng php khoanh giy khuch tn.

Cefaclor

30 g

18

1517

14

16

32

M100-S21 O O Cefdinir Cefixime 5 g 5 g 20 19 1719 1618 16 15 1 1 2 2 4 4 Xem lu (16). (17) i vi khoanh giy khuch tn, khng p dng i vi chng Morganella spp. Xem lu (17). (19) Bi v cc chng Providencia spp. c bo co cho kt qu nhy cm gi vi cefprozil, cc chng ny khng nn th nghim v bo co kt qu nhy cm bng phng php khoanh giy khuch tn. Xem lu (17). (19) Ch dng cho cc chng phn lp t ng tit niu. (20) Cc tiu chun c kt qu da trn liu dng 1g mi 8 gi. Xem lu (7).

O O

Cefpodoxime Cefprozil

10 g 30 g

21 18

1820 1517

17 14

2 8

4 16

8 32

Inv. Inv.

Cefetamet Ceftibuten

10 g 30 g

18 21

1517 1820

14 17

4 8

8 16

16 32

MONOBACTAMS C Aztreonam 30 g 21 1820 17 4 8 16

CARBAPENEMS (21) Theo nhng thng tin v c im dc ng hc (PK-PD) c nh gi, nhng thng tin lm sng cn mc gii hn, v khong phn b MIC thu c t c nhng chng c kh nng to ra carbapenemase, nhng xem xt li v tiu chun nh gi cho carbapenem c xut bn ln u thng 1 nm 2010 (M100-S20-U) v c trnh by y. Do s khim khuyt trong cc phc iu tr cho cc cn nguyn c gii hn nh gi c MIC v ng knh vng c ch ri vo gi tr khng trung gian, cc nh lm sng iu tr bng cch tng ti a lng carbapenem trong gii hn khuyn co v c l tng thi gian s dng thuc theo ng tim, nh l c bo co trong mt s cng trnh nguyn cu. Khi phn lp c cc chng m c kt qu MIC v ng knh vng c ch l khng hoc khng trung gian, tin hnh tho lun vi cc bc s lm sng chuyn khoa truyn nhim. Cho ti khi cc labo cha th b sung tiu chun din gii mi, th nghim Hodge ci tin MHT cn phi c tin hnh nh c m t trong phin bn cp nhn Bng 2A-3S. Sau khi tin hnh b sung tiu chun din gii mi, khng cn thit phi tin hnh MHT ngoi tr v mc ch Dch t v Chng nhim khun (tham kho Bng 2A-S2) Nhng thng tin di y c cung cp nh l nhng kin thc c bn v Enterobacteriaceae sinh carbapenemase. Phn ln nhng chng ny c MIC v ng knh vng c ch trong gi tr ca khng trung gian v khng. l l do vi sao phi thit lp li gii hn nng c ch ti

M100-S21 thiu v ng knh vng c ch vi nhm carbapenem. Hiu qu iu tr ca carbapenem vi cc nhim trng gy ra bi cc chng c MIC v ng knh vng c ch vi carbapenem trong khong khng trung gian l khng chc chn do thiu nhng nhng nghin cu lm sng i chng. MIC (khong gi hn ca khng v trung gian) ca imipenem vi Proteus spp., Providencia spp., v Morganella morganii c xu hng cao hn MIC ca meropenem hoc doripenem. C ch lm tng MIC nhng chng ny ngoi do carbapenemase cn c nhng c ch khc. B Doripenem 10 g 23 20-22 19 1 2 4 (22) Tiu chun din gii kt qu da trn liu 500 mg mi 8 gii B Ertapenem 10 g 23 20-22 19 0,25 0,5 1 (23) Tiu chun din gii kt qu da trn liu 1 g mi 24 gii Imipenem 10 g 23 20-22 19 1 2 4 (24) Tiu chun din gii kt B qu da trn liu 500 mg mi 6 gii hoc 1 g mi 8 gii B Meropenem 10 g 23 20-22 19 1 2 4 (25) Tiu chun din gii kt qu da trn liu 1 g mi 8 gii AMINOGLYCOSIDES (26) CNH BO: i vi Salmonella spp. v Shigella spp., cc khng sinh nhm aminoglycoside c th c tc dng in vitro nhng khng c hiu qu trn lm sng v khng nn bo co kt qu nhy cm. A Gentamicin 10 g 15 1314 12 4 8 16 A Tobramycin 10 g 15 1314 12 4 8 16 B Amikacin 30 g 17 1516 14 16 32 64 O O O Kanamycin Netilmicin Streptomycin 30 g 30 g 10 g 18 15 15 1417 1314 1214 13 12 11 16 8 32 16 64 32 (27) Khng c tiu chun c kt qu MIC.

TETRACYCLINES (28) Cc chng vi khun nhy cm vi tetracycline cng c th xem nh nhy cm vi doxycycline v minocycline. Tuy nhin, mt s chng khng hoc khng trung gian vi tetracycline c th vn nhy cm vi doxycycline v/hoc minocycline. C Tetracycline 30 g 15 1214 11 4 8 16 O Doxycycline 30 g 14 1113 10 4 8 16

M100-S21 O Minocycline 30 g 16 1315 12 4 8 16 FLUOROQUINOLONES (29) Cc chng Salmonella nhy cm vi fluoroquinolone, khi xt nghim cho kt qu khng vi nalidixic axit c th dn n tht bi trn lm sng hoc p ng chm trn bnh nhn nhim vi khun thng hn ngoi rut iu tr vi fluoroquinolones. Cc chng Salmonella ngoi rut nn c xt nghim tnh khng vi axit nalidixic. i vi cc chng nhy cm vi fluoroquinolones v khng vi axit nalidixic, nn thng tin cho bc s rng cc chng khng th b loi tr khi iu tr bng fluoroquinolone. Tham kho kin cc chuyn gia v bnh nhim khun. Xem lu (2). B B U U U O O O O Inv.

Ciprofloxacin Levofloxacin Lomefloxacin hoc ofloxacin Norfloxacin Enoxacin Gatifloxacin Gemifloxacin Grepafloxacin Fleroxacin

5 g 5 g 10 g 5 g 10 g 10 g 5 g 5 g 5 g 5 g 100 g 30 g

21 17 22 16 17 18 18 20 18 19 19 19

1620 1416 1921 1315 1316 1517 1517

15 13 18 12 12 14 14

1 2 2 2 4 2 2 0.25 1 2 16 16

2 4 4 4 8 4 4 0.5 2 4 32

4 8 8 8 16 8 8 1 4 8 64 32 Xem lu (19) (31) i vi cc chng phn lp t nc tiu, c th s dng axit nalidixic th nghim gim nhy cm vi fluoroquinolone ca cc chng phn lp t bnh nhn nhim Salmonella ngoi rut. Xem lu (19) v (29). (30) FDA ph duyt s dng i vi Klebsiella pneumoniae

1619 15 1517 14 1618 15 1518 1418 14 13

QUINOLONES O Cinoxacin O Nalidixic axit

C CH CON NG FOLATE B Trimethoprimsulfamethoxazole

1.25/23.75 g

16

1115

10

2/38

4/76

Xem lu (2).

Sulfonamides

250 hoc 300 g 5 g 30 g

17

1316

12

256

512

M100-S21 (32) Sulfisoxazole c th i din cho cc khng sinh nhm sulfonamide khc.

Trimethoprim

16 18

1115 1317

10 12

8 8

16

16 32 (33) Khng bo co thng qui vi cc chng phn lp t nc tiu. (34) Ch nh i vi cc chng E. coli phn lp t ng tit niu. (35) Khoanh khng sinh fosfomycin hm lng 200-g cha 50 g glucose-6-phosphate. (36) S dng phng php pha long trn thch xc nh MIC. Mi trng thch nn b sung vi 25 g/mL of glucose-6phosphate. Khng nn tin hnh phng php pha long trn thch.

PHENICOLS C Chloramphenicol

FOSFOMYCINS O Fosfomycin

200 g

16

1315

12

64

128

256

NITROFURANS U Nitrofurantoin

300 g

17

1516

14

32

64

128

M100-S21 Bng thng tin thm 2A-S1. Th nghim sng lc v khng nh ESBL cc chng Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, v Proteus mirabilisa i vi cc trng hp Bng 2A LU : Theo nhng thng tin v c im dc ng hc c nh gi v cc thng tin lm sng cn hn ch, cc tiu chun din gii kt qu mi i vi cc cephalosporins (cefazolin, cefotaxime, ceftazidime, ceftizoxime, v ceftriaxone) v aztreonam c cng b ln u vo thng 1 nawmg 2010 (phin bn M100-S20) v lit k trong bng 2A. Cefepime v cefuroxime (ng tim) cng c nh gi; tuy nhin, khng c s thay i v tiu chun c kt qu i vi cc liu lng trnh by trong Bng 2A. Khi s dng cc tiu chun c kt qu mi, khng cn thit tin hnh th nghim ESBL thng qui trc khi bo co kt qu (v d, khng cn iu chnh tiu chun c kt qu khng i vi cephalosporins, aztreonam, hoc penicillins). Tuy nhin, vn nn tin hnh xt nghim ESBL nh m t trong bng di y cho n khi phng xt nghim p dng tiu chun c kt qu mi. Th nghim ESBL c th vn c ch cho dch t hc v cng tc chng nhim khun. Xt nghim Phng php xt nghim Mi trng Nng khng sinh Xt nghim sng lc ban u Khoanh giy khuch tn Vi pha long trn canh thang MHA i vi K. pneumoniae, K. oxytoca, v E. coli: Cefpodoxime 10 g hoc Ceftazidime 30 g hoc Aztreonam 30 g hoc Cefotaxime 30 g hoc Ceftriaxone 30 g i vi P. mirabilisa: Cefpodoxime 10 g hoc Ceftazidime 30 g hoc Cefotaxime 30 g (S dng hn mt khng sinh i vi xt nghim sng lc gip tng nhy pht hin) Huyn dch vi khun Khuyn co s dng khoanh giy khuch tn chun CAMHB i vi K. pneumoniae, K. oxytoca, v E. coli: Cefpodoxime 4 g/mL hoc Ceftazidime 1g/mL hoc Aztreonam 1 g/mL hoc Cefotaxime 1 g/mL hoc Ceftriaxone 1 g/mL i vi P. mirabilisa: Cefpodoxime 1 g/mL hoc Ceftazidime 1 g/mL hoc Cefotaxime 1 g/mL (S dng hn mt khng sinh i vi xt nghim sng lc gip tng nhy pht hin) Khuyn co s dng canh thang pha long chun Xt nghim xc nh kiu hnh Khoanh giy khuch tn Vi pha long trn canh thang MHA CAMHB Ceftazidime 30 g Ceftazidime Ceftazidime-clavulanic 0.25 128 g/mL 30/10 g axitb Ceftazidime-clavulanic axit 0.25/4128/4 g/mL v v Cefotaxime 30 g Cefotaxime-clavulanic Cefotaxime 30/10 g axitb 0.25 64 g/mL Cefotaxime-clavulanic axit (Xt nghim khng nh 0.25/464/4 g/mL yu cu s dng c cefotaxime v (Xt nghim khng nh ceftazidime, n c hoc yu cu s dng c phi hp vi axit cefotaxime v ceftazidime, clavulanic) n c hoc phi hp vi axit clavulanic) Khuyn co s dng khoanh giy khuch tn chun Khuyn co s dng canh thang pha long chun

iu kin nui cy

35 2 C; hiu kh

35 2 C; hiu kh 16-20h Pht trin ti hoc cao hn nng sng lc c th cho thy kh nng sinh ESBL (v d, i vi E. coli, K. pneumoniae, v K. oxytoca, MIC 8 g/mL i vi cefpodoxime hoc MIC 2 g/mL i vi ceftazidime, aztreonam, cefotaxime, hoc ceftriaxone; v i vi P. mirabilis, MIC 2 g/mL i vi cefpodoxime, ceftazidime, hoc cefotaxime).

35 2 C; hiu kh 16-18h Tng ng knh vng c ch 5-mm i vi mt khng sinh khi phi hp vi clavulanic axit so vi ng knh vng c ch khi dng khng sinh n c = ESBL (v d, ceftazidime cho vng = 16; ceftazidimeclavulanic axit cho vng = 21).

M100-S21 35 2 C; hiu kh 16-20h Gim nng MIC 3 ln i vi mt khng sinh khi dng phi hp vi axit clavulanic so vi gi tr MIC ca khng sinh khi dng n c = ESBL (v d, ceftazidime MIC = 8 g/mL; ceftazidime-axit clavulanic MIC = 1 g/mL).

Thi gian nui cy 16-18h i vi K. pneumoniae, K. oxytoca, v Kt qu E. coli: Cefpodoxime zone 17 mm Ceftazidime zone 22 mm Aztreonam zone 27 mm Cefotaxime zone 27 mm Ceftriaxone zone 25 mm i vi P. mirabilisa: Cefpodoxime zone Ceftazidime zone Cefotaxime zone 22 mm 22 mm 27 mm

ng knh vng c ch nh trn c th cho thy kh nng sinh ESBL. Bo co i vi cc chng sinh ESBL: Nu phng xt nghim cha p dng cc tiu chun c kt qu mi i vi cephalosporin v aztreonam, nn bo co kt qu khng vi tt c cc khng sinh nhm penicillin, cephalosporin v aztreonam. Nu phng xt nghim p dng cc tiu chun mi i vi cephalosporin v aztreonam, khng cn thay i cc xt nghim i vi cc khng sinh ny. Khi tin hnh xt nghim Khi tin hnh xt nghim xc nhn ESBL, K. xc nh ESBL, K. pneumoniae pneumoniae ATCC 700603 hoc E. ATCC 700603 hoc E. coli ATCC 25922, nn coli ATCC 25922, nn c dng cho kim sot c dng kim sot cht lng thng qui (v cht lng thng qui (v d, hng tun hoc hng d, hng tun hoc hng ngy). ngy).

Cc xut v QC Khi xt nghim sng lc ESBL, K.pneumoniae ATCC 700603 c th l chng QC b sung (v d, cho tp hun, hi thao, nh gi xt nghim). Cc chng khc, K. pneumoniae ATCC 700603 hoc E. coli ATCC 25922, u c th s dng i vi kim sot cht lng thng qui (v d, hng tun hoc hng ngy).

Khi xt nghim sng lc ESBL, K. pneumoniae ATCC 700603 c th l chng QC b sung (v d, cho tp hun, hi thao, nh gi xt nghim). Cc chng khc, K. pneumoniae ATCC 700603 hoc E. coli ATCC 25922,

E. coli ATCC 25922 (xem cc gii hn v kim sot trong Bng 3) K. pneumoniae ATCC 700603: Cefpodoxime ng knh vng c ch 916 mm Ceftazidime ng knh vng c ch 1018 mm Aztreonam ng knh vng c ch 9 17 mm Cefotaxime ng knh vng c ch 1725 mm Ceftriaxone ng knh vng c ch 1624 mm

u c th s dng i vi kim sot cht lng thng qui (v d, hng tun hoc hng ngy). E. coli ATCC 25922 = Khng pht trin (xem cc gii hn v kim sot trong Bng4A). K. pneumoniae ATCC 700603 = Pht trin: Cefpodoxime MIC 8 g/mL Ceftazidime MIC 2 g/mL Aztreonam MIC 2 g/mL Cefotaxime MIC 2 g/mL Ceftriaxone MIC 2 g/mL

E. coli ATCC 25922: tng 2-mm ng knh vng c ch ca khng sinh n so vi khng sinh phi hp vi axit clavulanic. K. pneumoniae ATCC 700603: tng 5-mm ng knh vng c ch ceftazidime-clavulanic axit; tng 3-mm ng knh vng c ch cefotaximeclavulanic axit.

M100-S21 E. coli ATCC 25922: gim <3 ln nng MIC ca khng sinh phi hp vi axit clavulanic K. pneumoniae ATCC 700603:gim 3 ln nng MIC ca khng sinh phi hp vi axit clavulanic so vi khng sinh khi th n c.

Vit tt: ATTC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB: Canh thang Mueller-Hinton iu chnh cation; ESBL: men -lactamase ph rng; MHA: thch Mueller-Hinton; MIC: nng ti thiu c ch; Ghi ch a. Sng lc Proteus mirabilis sinh ESBL ch i vi cc chng quan trng v lm sng (v d, chng nhim khun huyt) b. Chun b khoanh giy ceftazidime-axit clavulanic (30 g/10 g) v cefotaxime-axit clavulanic (30 g/10 g): S dng dung dch m axit clavulanic nng 1000 g/mL (hoc chun b mi t mt lng nh ng bng 70 C), thm 10 L axit clavulanic vo khoanh giy ceftazidime (30 g) v cefotaxime (30 g). S dng micropipette nh 10 L dung dch m ln khoanh giy ceftazidime v cefotaxime trong vng 1h trc khi t ln a, c th ch cn 30 pht axit clavulanic hp ph ln khoanh giy khng sinh, kh v t ln a. S dng cc khoanh giy sau khi chun b hoc vt b, khng gi li cho ln sau..

M100-S21 Bng b sung 2A-S2. Xt nghim khng nh cc chng nghi ng sinh Carbapenemase Enterobacteriaceae khi s dng tiu chun din gii kt qu mi cho carbapenem Ch khi no s dng tiu chun din gii mi cho carbapenem c cng b vo thng 1 nm 2010 (M100-S20-U) 1. Xt nghim sng lc ban u (c trnh by trong bng b sung 2A-S3) v xt nghim xc nhn (vd, MHT) l khng cn thit cho xt nghim thng quy trn bnh nhn. 2. Xt nghim MHT c l hu dng cho vic xt nghim cc chng v mc ch dch t hc hoc chng nghim khun 3. Khng c s thay i no trong din gii kt qu xt nghim nhy cm carbapenem i vi cc chng cho kt qu dng tnh vi th nghim Hodge ci tin (MHT). Khi thc hin xt nghim ny: Nhng quy trnh kim sot nhim khun hoc cc cuc kho st dch t hc yu cu xc nh nhng chng thuc Enterbacteriaceae sinh carbapenemae. Cc chng sinh carbapenemase thng khng trung gian hoc khng vi mt hoc hn mt khng sinh thuc nhm carbapenem theo tiu chun din gii c lit k trong bng 2A (ch : khng nhy cm vi Ertapenem l mt biu hin nhy nht ca sinh carbapenemase). Hoc cac chng ny thng khng vi mt hoc trn mt khng sinh thuc cephalosporin nhm III (vd, cefoperazone, cefotaxime, ceftazidime, ceftizoxime v ceftriaxone. Do , xt nghim ny ch gii hn vi cc chng c biu hin trn. Xt nghim Hodge iu chnh MHA Khoanh Ertapenem 10 g hoc Khoanh Meropenem 10 g (1) Chun b huyn dch vi khun E. coli ATCC 25922 (chng ch nh) trong nc mui hoc canh thang vi m chun 0.5 McFarland (pha long trc tip t khun lc hoc qua tng sinh) sau pha long 1:10 trong nc mui hoc canh thang. Cy huyn dch chng ch nh pha long 1:10 trn a MHA nh phng php khng sinh thng qui. a kh t nhin 3 n 10 pht. t s khoanh giy ertapenem hoc meropenem trn a vi s lng nh lu sau y v trong Hnh 1 v 2. (2) S dng u que cy trn (vng u que cy c th tch 10-L) hoc tm bng nht 35 khun lc chng cn xt nghim hoc chng chun c tng sinh qua m. Dng que cy hoc tm bng c khun lc cn lm xt nghim vch mt ng thng t mp ca khoanh bi mp ca ia. ng cy t nht 2025 mm. S chng xt nghim trong mi a nh lu sau y v trong Hnh 1 v 2. S lng chng/khoanh giy xt nghim trong a MHA nh v ln (100-mm hoc 150-mm, tng ng): Nh Ln S khoanh giy 1 14 Cc chng xt nghim 1 16 Cc chng QC 2 2 35 2 C; hiu kh

Phng php xt nghim Mi trng Nng khng sinh Huyn dch vi khun

iu kin nui cy

M100-S21 Thi gian nui cy Kt qu 16-20h

Sau khi tng sinh, trn MHA kho st s tng sinh (biu hin bng cc khun lc to thnh hnh lan qut) ti vng giao thoa gia vt cy v chu vi vng c ch ca chng ch nh (E. coli ATCC 25922) nh m t di (Hnh 1 v 2). C tng sinh = carbapenemase dng tnh. Khng tng sinh = carbapenemase m tnh. Mt s vi khun c th sinh cht c ch s pht trin ca E. coli ATCC25922. Nu c s c ch ny, s xut hin mt vng sng xung quanh vt cy (xem Hnh 3). Nh vy xt nghim Hodge iu chnh khng thch hp vi nhng chng ny. i vi cc chng dng tnh vi xt nghim Hodge, tin hnh xt nghim MIC trc khi bo co kt qu i vi carbapenem. Mi kt qu bo co u da duy nht vo MIC. Bo co Bo co kt qu ca th nghim Hodge ci tin cho khoa chng nhim khun, hoc ti cc khoa c chc nng dch t hc. Khng c s thay i no trong din gii kt qu xt nghim nhy cm carbapenem i vi cc chng cho kt qu dng tnh vi th nghim Hodge ci tin (MHT) Chng chun Kim tra cc chng chun dng tnh v m tnh mi ngy c xt nghim khuyn co K. pneumoniae ATCC BAA-1705xt nghim Hodge dng tnh K. pneumoniae ATCC BAA-1706xt nghim Hodge m tnh Vit tt: ATTC tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; KPC, K. pneumonia sinh men carbapenemases; MHA, Thch Mueller-Hinton; MHT, Th nghim Hodge ci tin (Modified Modge test); MIC, Nng c ch ti thiu; QC, kim sot cht lng

M100-S21 Bng 2A-S2. (Tip) Lu : 1. Xt nghim sng lc v khng nh theo khuyn co phn ln xut pht t cc chng Enterobacteriaceae Theo tiu h thng th nghim Hoa K v cho nhy (>90%) v c hiu (>90%) cao v kh nng pht hin kiu sinh carbapenemase loi(KPC) nhng chng ny. nhy v c hiu ca xt nghim pht hin kh nng sinh metallo--lactamase cn mc thp. 2. Khng c d liu v s cn thit ca cc xt nghim pht hin kh nng sinh carbapenemase trc khun Gram m khng ln men.

E. coli ATCC25922

Vng c ch E. coli ATCC25922 bng ertapenem C tng sinh E. coli ATCC25922. K. pneumoniae ATCCBAA-1705 sinh carbapenemase gy bt hot ertapenem trong mi trng. Do , khng c ertapenem c ch E. coli ATCC25922 v lu v s lm vo ca vng c ch (hnh lan qut). Hnh 1. MHT tin hnh trn a MHA nh (1) K. pneumoniae ATCCBAA-1705, kt qu dng tnh; (2) K. pneumoniae ATCCBAA-1706, kt qu m tnh; (3) Chng lm sng, kt qu dng tnh

M100-S21

Hnh 2. MHT thc hin trn a MHA ln vi Ertapenem. (1) K. pneumoniae ATCCBAA-1705, kt qu dng tnh; (2) K. pneumoniae ATCCBAA-1706, kt qu m tnh; (3-8) Chng lm sng; (6) kt qu m tnh; (3,4,5,7,8) kt qu dng tnh.

Hnh 3. V d v kt qu khng r rng. (1) Chng lm sng vi kt qu khng r rng (chng c ch s pht trin ca E. coli ATCC25922; (2) chng lm sng vi kt qu m tnh

M100-S21 Bng b sung 2A-S3. Xt nghim sng lc v xc nhn cc chng Enterobacteriaceae nghi ng sinh carbapenemase khi s dng tiu chun din gii kt qu Carbapenem C (S dng vi bng 2A trong phin bn M100-S20 [Thng 1 nm 2010]) Cho ti khi tiu chun din gii mi c b sung cho carbapenem, cc th nghim sng lc v xc nhn phi c thc hin v bo co theo nhng ch dn mi cho cc trng hp MHT dng tnh c m t nh di y. Khng cn thit tin hnh th nghim carbapenemase cho mi chng bng th nghim MHT khi m tt c cc khng sinh ca nhm carbapenem u c bo co l khng trung gian hoc khng. Xt nghim Khi thc hin xt nghim ny Phng php xt nghim Mi trng Nng khng sinh Xt nghim sng lc ban u CH p dng nhng iu sau khi m s dng tiu chun din gii kt qu cho carbapenam c trnh by trong M100-S20 (thng 1 nm 2010) Khng sinh Vi pha long canh thang MHA Ertapenem 10 g hoc Meropenem 10 g (LU : Xt nghim dng khoanh giy imipenem sng lc carbapenemases thng km hiu qu) Khuyn co s dng phng php khng sinh tiu chun CAMHB Ertapenem 1 g/mL hoc Imipenem 1 g/mL hoc Meropenem 1 g/mL Xt nghim khng nh kiu hnh Xt nghim sng lc dng tnh v khng vi mt hoc mt s khng sinh cephalosporin th h III (v d, cefoperazone, cefotaxime, ceftazidime, ceftizoxime v ceftriaxone) Xt nghim Hodge iu chnh MHA Khoanh Ertapenem 10 g hoc Khoanh Meropenem 10 g

Huyn dch vi khun

Khuyn co s dng phng php pha long chun

(1) Chun b huyn dch vi khun E. coli ATCC 25922 (chng ch nh) bng nc mui sinh l hoc canh thang vi m 0.5 McFarland (s dng hoc trc tip t khun lc hoc qua tng sinh) sau pha long 1:10 trong nc mui hoc canh thang. Cy trn a MHA nh phng php khng sinh thng qui. a kh t nhin 3 n 10 pht. t s khoanh giy ertapenem hoc meropenem trn a nh lu sau y v trong Hnh 1 v 2. (2) S dng u que cy vng (10-L) hoc tm bng, nht 35 khun lc chng cn xt nghim hoc chng chun c tng sinh qua m trn thch mu v cy ng thng t mp ca khoanh giy ertapanem vi mp ca a thch. Cy mt ng t nht 2025 mm. Xt nghim s chng mi a nh lu sau y v trong Hnh 1 v 2. S lng khoanh giy v chng th nghim ca a MHA nh v ln (100-mm hoc 150-mm, tng ng): Nh Ln

M100-S21 S khoanh giy Cc chng xt nghim Cc chng QC 35 2 C; hiu kh 16-20h Sau khi tng sinh, trn MHA kho st s tng sinh (biu hin bng cc khun lc to thnh hnh lan qut) ti vng giao thoa gia vt cy v chu vi vng c ch ca chng ch nh (E. coli ATCC 25922) (Hnh 1 v 2). C tng sinh = carbapenemase dng tnh. Khng tng sinh = carbapenemase m tnh. Mt s vi khun c th sinh cht c ch s pht trin ca E. coli ATCC25922. Nu c s c ch ny, s xut hin mt vng sng xung quanh vt cy (xem Hnh 3). Nh vy xt nghim Hodge iu chnh khng thch hp vi nhng chng ny. i vi cc chng dng tnh vi th nghim sng lc bng khoanh giy ertapenem hoc meropenem V xt nghim Hodge dng tnh, tin hnh xt nghim MIC trc khi bo co kt qu i vi mi carbapenem. Mi kt qu bo co u da duy nht vo MIC. CH p dng nhng iu sau khi m s dng tiu chun din gii kt qu cho carbapenam c trnh by trong M100-S20 (thng 1 nm 2010) i vi cc chng m xt nghim Hodge dng tnh v MIC ca ertapenem khong 2-4 g/mL; MIC ca imipenem 2-8 g/mL; hoc MIC ca meropenem 2-8 g/mL, bo co kt qu mi carbapenem u b khng Nu MHT m tnh, din gii kt qu MIC ca carbapenem theo tiu chun din gii ca CLSI c trnh by trong Bng 2A trong phin bn M100-S20 (thng 1 nm 2010) 1 1 2 14 16 2

35 2 C; hiu kh iu kin nui cy Thi gian nui 16-18h cy Ertapenem 1621 mm Kt qu Meropenem 1421 mm Cc ng knh vng c ch nh trn chng t chng vi khun xt nghim sinh carbapenemase, mc d thc t cc chng vn trong danh sch nhy cm. khng nh, tin hnh xt nghim Hodge. (LU : Khoanh giy imipenem khng thch hp cho sng lc carbapenemases.)

35 2 C; hiu kh 16-20h Ertapenem 2-4 g/mL Imipenem 28 g/mL Meropenem 28 g/mL Cc gi tr MIC nh trn chng t chng vi khun xt nghim sinh carbapenemase, mc d thc t cc chng vn trong danh sch nhy cm theo nh phin bn M100-S20 (thng 1 nm 2010)

Bo co

M100-S21 Kim tra cc chng chun dng tnh v m tnh mi ngy c xt nghim K. pneumoniae ATCC BAA-1705xt nghim Hodge dng tnh K. pneumoniae ATCC BAA-1706xt nghim Hodge m tnh Vit tt: ATTC tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; KPC, K. pneumonia sinh men carbapenemases; MHA, Thch Mueller-Hinton; MHT, Th nghim Hodge ci tin (Modified Modge test); MIC, Nng c ch ti thiu; QC, kim sot cht lng Khuyn co kim sot cht lng S dng E. coli ATCC 25922 trong kim sot cht lng thng qui. S dng E. coli ATCC 25922 trong kim sot cht lng thng qui.

M100-S21 Bng 2A-S3. (Tip) Lu : 1. Proteus spp., Providencia spp., v Morganella spp. c MIC vi imipenem cao hn bi nhng c ch khc khng ch bi carbapenamase, do , MIC ca imipenem cho cc test sng lc xc nh carbapenemase 3 tc ny khng c xc lp. Tng t nh vy, khoanh giy imipenem th nghim sng lc carpabenemase Enterobacteriaceae c gi tr rt thp. 2. Xt nghim sng lc v khng nh theo khuyn co phn ln xut pht t cc chng Enterobacteriaceae Theo tiu h thng th nghim Hoa K v cho nhy (>90%) v c hiu (>90%) cao v kh nng pht hin kiu sinh carbapenemase loi(KPC) nhng chng ny. nhy v c hiu ca xt nghim pht hin kh nng sinh metallo--lactamase cn mc thp. 3. Khng c d liu v s cn thit ca cc xt nghim pht hin kh nng sinh carbapenemase trc khun Gram m khng ln men.

E. coli ATCC25922

Vng c ch E. coli ATCC25922 bi ertapenem C tng sinh E. coli ATCC25922. K. pneumoniae ATCCBAA-1705 sinh carbapenemase gy bt hot ertapenem trong mi trng. Do , khng c ertapenem c ch E. coli ATCC25922 v lu v s lm vo ca vng c ch (hnh lan qut). Hnh 1. MHT tin hnh trn a MHA nh (1) K. pneumoniae ATCCBAA-1705, kt qu dng tnh; (2) K. pneumoniae ATCCBAA-1706, kt qu m tnh; (3) Chng lm sng, kt qu dng tnh

M100-S21

Hnh 2. MHT thc hin trn a MHA ln vi Ertapenem. (1) K. pneumoniae ATCCBAA-1705, kt qu dng tnh; (2) K. pneumoniae ATCCBAA-1706, kt qu m tnh; (3-8) Chng lm sng; (6) kt qu m tnh; (3,4,5,7,8) kt qu dng tnh.

Hnh 3. V d v kt qu khng r rng. (1) Chng lm sng vi kt qu khng r rng (chng c ch s pht trin ca E. coli ATCC25922; (2) chng lm sng vi kt qu m tnh

M100-S21 Bng 2B-1. Tiu chun c kt qu ng knh vng c ch v nng c ch ti thiu tng ng (MIC) i vi Pseudomonas aeruginosa iu kin th nghim Mi trng: Khoanh giy khuch tn: MHA Pha long canh thang: CAMHB Pha long trn thch: MHA Cy chuyn vi khun qua canh thang hoc pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352oC, hiu kh, Khng sinh : 16-18h Phng php pha long: 16-20h Cc xut kim sot cht lng ti thiu (Xem bng 3A v 4A: gii hn QC cho php) Escherichia coli ATCC 25922 Pseudomonas aeruginosa ATCC 27853 Escherichia coli ATCC 35218 (dng cho phi hp -lactam/c ch men lactamase)

Huyn dch vi khun:

iu kin nui cy:

Lu chung (1) Khoa giy khuch tn: o ng knh vng c ch ( bng mt thng), bao gm ng knh khoanh giy. Soi a trn nn en vi nh sng xuyn qua. Ranh gii vng c ch xc nh bng mt vng khng c bt k khun lc no c th pht hin bng mt thng, b qua cc khun lc li ti mp m ch c th pht hin di knh hin vi. Cc chng Proteus spp., c th pht trin lan vo vng c ch i vi tng loi khng sinh nht nh. i vi chng Proteus spp., b qua s pht trin yu trong trng hp vng v khun khng r rng. i vi trimethoprim v sulfonamides, cht i khng trong mi trng c th cho php vi khun pht trin yu, do , nu vi khun pht trin mc khong 20% hoc t hn th c th khng quan tm v o ng knh vng c ch ranh gii r rng nht. (2) S nhy cm ca P. aeruginosa phn lp t bnh nhn b bnh s ha h thng c th khng nh bng phng php khoanh giy khuch tn, nhng cn tng thi gian nui cy ln 24h trc khi bo co kt qu nhy cm. (3) P. aeruginosa c th tr nn khng tt c cc loi khng sinh sau thi gian iu tr ko di. Do , cc chng ny ban u c th nhy cm nhng sau 3-4 ngy iu tr tr nn khng thuc. Cn tin hnh th nghim lp li. (4) im nhy cm-gii hn (breakpoint) trong cc bng i y da trn hm lng khng sinh t do trong huyt tng ngi (c chc nng gan v thn bnh thng). Khi mt im nhy cm mi c b sung, khoa xt nghim phi chia s nhng thng tin ny ti cc Bc s chuyn khoa truyn nhim, cc dc s, Hi ng thuc v iu tr, v Khoa chng nhim khun. Thng tin v k n cn phi c sot xt li v cc nh lm sng phi tin hnh hi chn xc nh liu lng iu tr cho bnh nhn nhim trng c bit..

M100-S21 LU : Nhm th nghim/ bo co Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc . Khng sinh Hm lng Gii hn ng knh vng c ch (mm) S I R Gii hn nng c ch ti thiu (g/mL) S I R Lu

PENICILLINS (5) Rx: S phn chia kiu nhy cm, trung gian v khng hm rng cn thit dng khng sinh liu cao i vi cc trng hp nhim khun nng gy ra bi P. aeruginosa. i vi cc trng hp ny, liu php khng sinh n s gp tht bi trn lm sng. A Piperacillin 100 g 18 B Ticarcillin 75 g 15 O Azlocillin 75 g 18 O Carbenicillin 100 g 17 O Mezlocillin 75 g 16 PHI HP -LACTAM/ CHT C CH -LACTAMASE Xem ghi ch (5). B O Piperacillin-tazobactam Ticarcillin-clavulanic axit 100/10 g 75/10 g 18 15 14-16 17 14 17 13 15 64 64 64 128 64 256 128 128 128 512 128

17 14

64/4 64/2

128/4 128/2 (6) Tiu chun din gii kt qu da trn liu 1 gam mi 6 gii hoc 2 g mi 8 gii (7) Tiu chun din gii kt qu da trn liu 1 gam mi 8 gii hoc 2 g mi 12 gii

CEPHEMS (Bao gm cephalosporins th h I, II, III, v IV. Tham kho ph lc I.)

Ceftazidime

30 g

18

15-17

14

16

32

Cefepime

30 g

18

15-17

14

16

32

MONOBACTAMS B Aztreonam

30 g

22

16-21

15

16

32

(8) Tiu chun din gii

M100-S21 kt qu da trn liu 1 gam mi 6 gii hoc 2 g mi 8 gii CARBAPENEMS B Imipenem B Meropenem LIPOPEPTIDES O Colistin O Polymyxin B AMINOGLYCOSIDES A Gentamicin A Tobramycin B Amikacin O Netilmicin FLUOROQUINOLONES B Ciprofloxacin B Levofloxacin U Lomefloxacin hoc U ofloxacin U Norfloxacin O Gatifloxacin 10 g 10 g 10 g 300 n v 10 g 10 g 30 g 30 g 5 g 5 g 10 g 5 g 10 g 5 g 16 16 11 12 15 15 17 15 21 17 22 16 17 18 14-15 14-15 13-14 13-14 15-16 13-14 16-20 14-16 19-21 13-15 13-16 15-17 13 13 10 11 12 12 14 12 15 13 18 12 12 14 4 4 2 2 4 4 16 8 1 2 2 2 4 2 8 8 4 4 8 8 32 16 2 4 4 4 8 4 16 16 8 8 16 16 64 32 4 8 8 8 16 8

(9) Tiu chun ny p dng i vi cc chng phn lp t ng tit niu. Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu;

M100-S21 Bng 2B-2. Tiu chun c kt qu ng knh vng c ch v nng c ch ti thiu (MIC) i vi Acinetobacter spp. iu kin th nghim Mi trng: Khoanh giy khuch tn: MHA Pha long canh thang: CAMHB Pha long trn thch: MHA Phng php tng sinh bng canh thang hoc pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352oC, hiu kh, 20-24h, tt c cc phng php Lu chung (1) i vi khoa giy khuch tn, o ng knh vng c ch (bng mt thng), bao gm ng knh khoanh giy. Soi a trn nn en vi nh sng xuyn qua. Ranh gii vng c ch xc nh bng mt vng khng c bt k khun lc no c th pht hin bng mt thng, b qua cc khun lc li ti mp m ch c th pht hin di knh hin vi.. i vi trimethoprim v sulfonamides, cc cht i khng trong mi trng c th cho php vi khun pht trin yu; do c th b qua s pht trin yu ny (khng qu 20%) v o ng knh vng c ch ranh gii r rng nht.. Cc yu cu kim sot cht lng ti thiu (Xem bng 3A v 4A: gii hn QC cho php) Escherichia coli ATCC 25922 Pseudomonas aeruginosa ATCC 27853 Escherichia coli ATCC 35218 (dng cho phi hp -lactam/c ch men -lactamase)

Huyn dch vi khun:

iu kin nui cy:

LU :

Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc . Gii hn ng knh vng c ch (mm) S I R 18-20 18-20 15-19 12-14 18-20 17 15 14 11 17 Gii hn nng c ch ti thiu (g/mL) S I R 16 16 16 8/4 16/4 3264 3264 3264 16/8 32/4-64/4 128 128 128 32/16 128/4 Lu

Nhm th nghim/ Khng sinh bo co PENICILLINS

Hm lng

B Piperacillin 100 g 21 O Mezlocillin 75 g 21 O Ticarcillin 75 g 20 PHI HP -LACTAM/ CHT C CH -LACTAMASE A Ampicillin-sulbactam 10/10 g 15 B Piperacillin100/10 g 21

M100-S21 tazobactam B Ticarcillin-clavulanic axit 75/10 g 20 15-19 14 16/2 32/2-64/2 128/2 32 32 64 64 16 16 4 4

CEPHEMS (NG TIM) (Bao gm cephalosporins th h I, II, III, v IV. Tham kho ph lc I.) A Ceftazidime 30 g 18 15-17 14 8 16 B Cefepime B Cefotaxime B Ceftriaxone CARBAPENEMS A Imipenem A Meropenem LIPOPEPTIDES O Polymyxin B O Colistin AMINOGLYCOSIDES 30 g 30 g 30 g 10 g 10 g 18 23 21 16 16 15-17 15-22 14-20 14-15 14-15 14 14 13 13 13 8 8 8 4 4 2 2 16 1632 1632 8 8 -

A Gentamicin 10 g 15 13-14 12 4 8 16 A Tobramycin 10 g 15 13-14 12 4 8 16 B Amikacin 30 g 17 15-16 14 16 32 64 C Netilmicin 8 16 32 TETRACYCLINES (2) Cc chng nhy cm vi tetracycline cng c xem nh nhy cm vi doxycycline v minocycline. Tuy nhin, mt s chng c th khng trung gian hoc khng vi tetracycline vn c th nhy cm i vi doxycycline v/hoc minocycline. B Tetracycline 30 g 15 12-14 11 4 8 16 B Doxycycline 30 g 13 10-12 9 4 8 16 B Minocycline 30 g 16 13-15 12 4 8 16 FLUOROQUINOLONES A Ciprofloxacin 5 g 21 16-20 15 1 2 4 A Levofloxacin 5 g 17 14-16 13 2 4 8 O Gatifloxacin 5 g 18 15-17 14 2 4 8 THUC C CH CON NG CHUYN HO FOLATE B Trimethoprimsulfamethoxazole 1.25/ 23.75 g 16 11-15 10 2/38 4/76

M100-S21 Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu;

M100-S21 Bng 2B-3. Tiu chun c kt qu ng knh vng c ch v nng c ch ti thiu tng ng (MIC) i vi Burkholderia cepacia iu kin th nghim Mi trng: Khng sinh : MHA Pha long canh thang: CAHMB Pha long trn thch: MHA Cy chuyn vi khun qua canh thang hoc pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352oC, hiu kh, 20-24h tt c cc phng php Lu chung (1) i vi khoa giy khuch tn, o ng knh vng c ch (bng mt thng), bao gm ng knh khoanh giy. Soi a trn nn en vi nh sng xuyn qua. Ranh gii vng c ch xc nh bng mt vng khng c bt k khun lc no c th pht hin bng mt thng, b qua cc khun lc li ti mp m ch c th pht hin di knh hin vi.. i vi trimethoprim v sulfonamides, cc cht i khng trong mi trng c th cho php vi khun pht trin yu; do c th b qua s pht trin yu ny (khng qu 20%) v o ng knh vng c ch ranh gii r rng nht.. Cc xut kim sot cht lng ti thiu (Xem bng 3A v 4A: gii hn QC cho php) Escherichia coli ATCC 25922 Pseudomonas aeruginosa ATCC 27853 Escherichia coli ATCC 35218 (dng cho phi hp -lactam/c ch men -lactamase)

Huyn dch vi khun:

iu kin nui cy:

LU :

Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc . Lu

Gii hn ng knh vng Gii hn nng c ch Nhm Khng sinh Hm c ch (mm) ti thiu (g/mL) th nghim/ lng bo co S I R S I R CEPHEMS (NG UNG) (Bao gm cephalosporins I, II, III, and IV. Tham kho ph lc I.) B Ceftazidime 30 g 21 1820 17 8 16 32 CARBAPENEMS B Meropenem 10 g 20 1619 15 4 8 16 TETRACYCLINES B Minocycline 30 g 19 1518 14 4 8 16 THUC C CH CON NG CHUYN HO FOLATE A Trimethoprim1.25/ 16 11-15 10 2/38 4/76

M100-S21 sulfamethoxazole 23.75 g

PHI HP -LACTAM/C CH -LACTAMASE B TicarcillinClavulanic axit FLUOROQUINOLONES B Levofloxacin PHENICOLS

16/2

32/2 64/2 4

128/2

(2) Khng bo co thng qui vi B Chloramphenicol 8 16 32 cc chng phn lp t nc tiu. Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu, QC, m bo cht lng xt nghim

M100-S21 Bng 2B-4. Tiu chun c kt qu ng knh vng c ch v nng c ch ti thiu tng ng (MIC) i vi Stenotrophomonas maltophilia iu kin th nghim Mi trng: Khng sinh : MHA Pha long canh thang: CAMHB Pha long trn thch: MHA Cy chuyn vi khun qua canh thang hoc pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352 oC, hiu kh, 20-24h tt c cc phng php Cc xut kim sot cht lng ti thiu (Xem bng 3A v 4A: gii hn QC cho php) Escherichia coli ATCC 25922 Pseudomonas aeruginosa ATCC 27853 Escherichia coli ATCC 35218 (dng cho phi hp -lactam/c ch men -lactamase)

Huyn dch vi khun:

iu kin nui cy:

(1)

Lu chung i vi khoa giy khuch tn, o ng knh vng c ch (bng mt thng), bao gm ng knh khoanh giy. Soi a trn nn en vi nh sng xuyn qua. Ranh gii vng c ch xc nh bng mt vng khng c bt k khun lc no c th pht hin bng mt thng, b qua cc khun lc li ti mp m ch c th pht hin di knh hin vi.. i vi trimethoprim v sulfonamides, cc cht i khng trong mi trng c th cho php vi khun pht trin yu; do c th b qua s pht trin yu ny (khng qu 20%) v o ng knh vng c ch ranh gii r rng nht..

LU :

Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc

M100-S21 Bng 2B-4. Nhm th nghim/ bo co Khng sinh Hm lng Gii hn ng knh vng c ch (mm) S PHI HP -LACTAM/C CH -LACTAMASE B Ticarcillinclavulanic axit 16/2 32/2 64/2 128/2 32 16 I R Gii hn nng c ch ti thiu (g/mL) S I R Lu

CEPHEMS (NG RUT) (Bao gm cephalosporins I, II, III, v IV. Tham kho Ph lc I.) B Ceftazidime 8 16 TETRACYCLINES B Minocycline FLUOROQUINOLONES 30 g 19 15-18 14 4 8

B Levofloxacin 5 g 17 14-16 THUC C CH CON NG CHUYN HO FOLATE Trimethoprim1.25/ A sulfamethoxazole 23.75 g 16 11-15 PHENICOLS

13

10

2/38

4/76

(2) Khng bo co thng qui i vi cc chng phn lp t B Chloramphenicol 8 16 32 tit niu. Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu, QC, m bo cht lng xt nghim

M100-S21 Bng 2B-5. Cc tiu chun c kt qu MIC (g/mL) i vi cc chng khng phi Enterobacteriaceae khc (Tham kho Lu 1) iu kin th nghim Mi trng: Huyn dch vi khun: Khng sinh : MHA Pha long canh thang: CAMHB Cy chuyn vi khun qua canh thang hoc pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352 oC, hiu kh, 16-20h Cc xut kim sot cht lng ti thiu (Xem bng 3A v 4A: gii hn QC cho php) Escherichia coli ATCC 25922 Pseudomonas aeruginosa ATCC 27853 Escherichia coli ATCC 35218 (dng cho phi hp -lactam/c ch men -lactamase)

iu kin nui cy:

Lu chung

(1)

Cc vi khun khng thuc nhm Enterobacteriaceae khc bao gm Pseudomonas spp. (khng P. aeruginosa) v cc vi khun d mc, khng ln men ng glucose, trc khun gram m khng k P. aeruginosa, Acinetobacter spp., Burkholderia cepacia, B. mallei, B. pseudomallei, v Stenotrophomonas maltophilia. Tham kho Bng 2B-2, 2B-3, v 2B-4 i vi xt nghim Acinetobacter spp., B. cepacia, v S. maltophilia, v ti liu CLSI M45 i vi Burkholderia mallei v B. pseudomallei.

LU : Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc Nhm th Khng sinh Hm Gii hn ng knh vng Gii hn nng c ch nghim/ lng c ch (mm) ti thiu (g/mL) bo co S I R S I R PENICILLINS A O O O Piperacillin Mezlocillin 16 16 16 16 16/2 3264 3264 3264 32 32/2 64/2 128 128 128 64 128/2

Lu

Ticarcillin Carbenicillin PHI HP -LACTAM/C CH -LACTAMASE B Ticarcillin-clavulanic axit Piperacillin-tazobactam

M100-S21 B 16/4 32/4-64/4 16 16 1632 1632 32 1632 1632 1632 8 8 4 4 8 8 32 16 128/2 32 32 64 64 64 64 64 32 16 16 8 8 16 16 64 32 CEPHEMS (NG RUT) (Bao gm cephalosporins I, II, III, v IV. Tham kho Ph lc I.) A Ceftazidime 8 B C C O O O Cefepime Cefotaxime Ceftriaxone Cefoperazone Ceftizoxime Moxalactam 8 8 8 16 8 8 8 4 4 2 2 4 4 16 8

MONOBACTAMS B Aztreonam CARBAPENEMS B Imipenem B Meropenem LIPOPEPTIDES O Colistin O Polymyxin B AMINOGLYCOSIDES A Gentamicin A B O Tobramycin Amikacin Netilmicin

TETRACYCLINES (2) Cc chng nhy cm vi tetracycline th cng xem nh nhy cm vi doxycycline v minocycline. Tuy nhin, mt s chng khng trung gian hoc khng vi tetracycline c th vn nhy cm vi doxycycline, minocycline, hoc c hai. U Tetracycline 4 8 16 O Doxycycline 4 8 16 O Minocycline 4 8 16

M100-S21 FLUOROQUINOLONES B B U U U Ciprofloxacin Levofloxacin Lomefloxacin hoc ofloxacin Norfloxacin 1 2 2 2 4 2 4 4 4 8 4 8 8 8 16 (3) Cc tiu chun din gi ny ch p dng cho cc chng phn lp t ng tit niu.

O Gatifloxacin THUC C CH CON NG CHUYN HO FOLATE Trimethoprimsulfamethoxazole B -

2/38

4/76 (4) Sulfisoxazole c th i din cho cc khng sinh nhm sulfonamide khc.

U Sulfonamides PHENICOLS

256

512

(5) Khng bo co thng qui i vi cc chng phn B Chloramphenicol 8 16 32 lp t tit niu. Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu, QC, m bo cht lng xt nghim

M100-S21 Bng 2C. Tiu chun c kt qu ng knh vng c ch v nng c ch ti thiu tng ng (MIC) i vi Staphylococcus spp. iu kin th nghim Mi trng: Khoanh giy khuch tn: MHA Pha long trn canh thang: CAMHB; CAMHB b sung 2% NaCl i vi oxacillin, methicillin v nafcillin; CAMHB b sung 50 g/mL canxi i vi daptomycin Pha long trn thch: MHA; MHA + 2% NaCl i vi oxacillin, methicillin v nafcillin. Pha long trn thch cha c nh gi i vi daptomycin Pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352oC, hiu kh, Khng sinh 16-18h; 24h (staphylococci coagulase m tnh v cefoxitin); Phng php pha long: 16-20h; Tt c cc phng php: 24h i vi oxacillin, methicillin, nafcillin v vancomycin. Nu nui cy nhit cao hn 35 oC c th khng pht hin c MRS. Cc xut kim sot cht lng ti thiu (Xem bng 3A v 4A: gii hn QC cho php) Staphylococcus aureus ATCC 25923 (Khng sinh ) Staphylococcus aureus ATCC 29213 (MIC) Escherichia coli ATCC 35218 (dng cho phi hp -lactam/c ch men -lactamase)

Huyn dch vi khun: iu kin nui cy:

Tham kho Bng 2C-S4 v 2C-S5 cui Bng 2C i vi cc khuyn co b sung v cc iu kin xt nghim, gi bo co v QC. Lu chung (1). i vi phng php khoanh giy khuch tn, o ng knh vng c ch (xc nh ranh gii vng c ch bng mt thng), bao gm ng knh khoanh giy. Soi a thch trn nn en vi nh sng phn chiu tr trng hp linezolid, oxacilin v vancomycin nn s dng nh sng xuyn qua (cm a trc n chiu). Vng c ch khng c s pht trin r rng ca vi khun. B qua s pht trin yu v cc khun lc nh li ti ch c th pht hin khi soi di knh lp hoc knh hin vi b ca vng c ch. i vi trimethoprim v sulfonamides, cc cht i khng trong mi trng c th cho php vi khun pht trin nh; do c th b qua s pht trin yu ny (khng qu 20%) v o ng knh vng c ch vi ranh gii xc nh

M100-S21 bng mt thng. Nu c bt k khun lc no trong vng c ch ca oxacillin, linezolid hoc vancomycin chng t c s khng i vi cc khng sinh . (2) V mt l thuyt, s khng cc thuc nhm penicillin bn vi men penicilinase (xem Bng ch thch I) c xem nh khng methicillin hoc khng oxacillin. MRSA l cc chng S. aureus biu hin c ch khng qua mecA hoc qua c ch khng methicillin khc, v d thay i i lc ca protein gn penicillin vi oxacillin (bin chng S. aureus [MOD-SA]). (3) i vi cc chng t cu vng Staphylococcus aureus nhy cm vi oxacillin v Staplylococci khng sinh men coagulase, nu tin hnh th nghim nhy cm i vi cc khng sinh sau: cephems ng ung, ngoi rut, phi hp khng sinh -lactam/cht c ch men -lactamase, v carbapenems, nn bo co kt qu theo tiu chun din gii thng qui. Xem ghi ch (4) v bo co kt qu nhm -lactam i vi cc chng khng oxacilline. (4) CNH BO: i vi S. aureus khng oxacillin v Staphylococci coagulase m tnh (MRS), cc khng sinh -lactam khc, v d, penicillins, phi hp -lactam/-lactamase, cephems (tr cc cephalosporin th h mi vi hot tnh chng li MRSA), v carbapenems, c th c tc dng in vitro, nhng khng c hiu qu trong iu tr. Kt qu ca cc khng sinh nhm -lactam khng k cc khng sinh cephalosporin c hot tnh khng MRSA cn c bo co kt qu l khng hoc khng bo co. Bi v phn ln cc trng hp c ghi nhn c p ng rt thp i vi liu php khng sinh nhm -lactam, hoc cc s liu trn lm sng cha thuyt phc v tnh hiu qu ca cc khng sinh ny. (5) Pht hin s khng oxacillin: Th nghim i vi mecA hoc protein c m ha bi gene mecA, protein 2a gn penicillin (PBP 2a, hay cn gi l PBP2'), l phng php chnh xc nht pht hin cc chng khng oxacillin v c th c s dng khng nh kt qu khng sinh i vi cc chng Staphylococci phn lp t cc trng hp nhim khun nng. Cc chng Staphylococci mang gen mecA hoc gen biu hin protein PBP 2a (sn phm ca gen mecA), c xem nh khng oxacillin v bo co vi kt qu khng oxacillin. Cc chng khng mang gen mecA hoc khng sinh PBP 2a th xem nh nhy cm vi oxacillin. Bi v cc c ch khc him gp hn c ch sinh men mecA, nn trong trng hp m tnh vi mecA hoc PBP 2a v gi tr MIC ca oxacillin 4 g/mL th c ghi nhn vi kt qu khng oxacillin. Cc chng ny c th nhy cm vi cefoxitin bng phng php khoanh giy khuch tn. (6) Khng khuyn co th nghim thng qui i vi S. saprophyticus phn lp t nc tiu, bi v cc trng hp nhim khun ny thng c p ng vi nng t c trong nc tiu ca cc khng sinh s dng trong iu tr nhim khun tit niu cp tnh, nhim trng tit niu khng bin chng (v d, nitrofurantoin, trimethoprim sulfamethoxazole, hoc khng sinh nhm fluoroquinolone).

(7)

M100-S21 i vi mt s cp vi khun/khng sinh, hin tng khng hoc him khi pht hin chng khng khng cho php xc nh bt k mt kt qu no ngoi nhy cm.. i vi cc chng cho kt qu khng nhy cm, ton b qu trinh phn lp nh danh v tin hnh th nghim nhy cm khng sinh cn c lm li (Xem Ph lc A).

(8)

i vi th nghim sng lc chng sinh beta-lactamase, khng oxacillin, khng oxacillin qua trung gian mecA, gim nhy cm vi vancomycin, v khng clindamycin suy din, tham kho Bng 2C-S4 cui Bng 2C i vi nhm S.aureus v Bng 2C-S5 i vi staphylococci khng sinh men coagulase cui Bng 2C. Ngoi ra, gii thch thm v s dng cefoxitin d on khng oxacillin qua trung gian mecA c th tham kho trong Phn 12 ti liu M07-A8 v Phn 11 ti liu M02-A10.

LU :

Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc

M100-S21 Bng 2C. (Tip) Nhm th nghim/ bo co Gii hn ng knh vng c ch (mm) S I R Gii hn nng c ch ti thiu (g/mL) S I R Lu

Khng sinh

Hm lng

PENICILLIN (9) Staphylococci nhy cm vi penicillin th cng nhy cm vi cc penicillins khc, phi hp -lactam/cht c ch -lactamase, cephems chng li staphylococci, v carbapenems c FDA ph duyt s dng trong iu tr i vi cc trng hp nhim staphylococcal. Cc chng nhy cm vi oxacillin, khng penicillin th khng vi cc khng sinh nhm penicillins khc khng bn vi men penicillinase, nhng nhy cm vi cc penicillins n nh vi penicillinase, phi hp -lactam/c ch -lactamase, cephems chng li staphylococci, v carbapenems. Staphylococci khng oxacillin th cng khng vi tt c cc khng sinh -lactam tr cc khng sinh cephalosporin th h mi c hot tnh khng MRSA. Do , tnh nhy cm hay khng i vi khng sinh nhm -lactam c th suy lun t th nghim vi penicillin hoc cefoxitin hoc oxacillin.Th nghim thng qui vi cc penicillins khc, cc phi hp -lactam/c ch -lactamase, cephems, v carbapenems l khng cn thit. (10) Nu la chn mt khng sinh nhm penicillin bn vi men penicillinase xt nghim th oxacillin l mt la chn v kt qu c th p dng cho cc penicillin bn vi penicillinase, cloxacillin, dicloxacillin, flucloxacillin, methicillin v nafcillin. Xem ghi ch (4).

Penicillin

10 n v

29

28

0.12

0.25

M100-S21 (11). S dng khoanh giy penicillin 10 n v thay v dng khoanh giy ampicillin cho th nghim xc nh cc chng t cu vng sinh men -lactamase khng penicillin, nhy cm vi oxacillin,. Penicillin phi c s dng th tnh nhy cm ca cc staphylococcus vi tt c cc khng sinh nhm penicillin bn vi men betalactamase, nh ampicillin, amoxicillin, azlocillin, carbenicillin, mezlocillin, piperacillin, and ticarcillin. Thc hin th nghim lactamase suy on nn tin hnh i vi cc chng S. aureusl c gi tr MIC penicillinl 0.12 g/mL hoc ng knh vng c ch 29 mm trc khi bo co kt qu l nhy cm vi penicillin. Cc chng staphylococcus mang gen to -lactamase nhng kt qu th nghim lactamase suy on m tnh l rt him. Do , i vi cc trng hp nhim khun nng i hi liu php penicillin cho iu tr, phng xt nghim

M100-S21 nn tin hnh lm MIC i vi penicillin v xt nghim sinh -lactamase suy on i vi tt cc chng phn lp trn cng bnh nhn. Xt nghim gen -lactamase blaZ bng phng php PCR c th c cn nhc.. Xem Bng 2C-S4v Bng 2C-S5 cui Bng 2C.

Oxacillin i vi S. aureus v S. lugdunensis.

30 g cefoxitin

13

11-12

10

2 (oxacillin)

4 (oxacillin)

M100-S21 i vi S. aureus

1 g oxacillin 30 g cefoxitin

2 (oxacillin) 4 (cefoxitin)

4 (oxacillin)

i vi S. lugdunensis.

22

21

8 i vi S.aureus v (cefoxitin) S.lugdunensis (12) Cefoxitin c th thay th cho oxacillin; bo co kt qu nhy cm hoc khng oxacillin da trn kt qu ca cefoxitin. (13) Nu c cefoxitin v oxacillin c xt nghim vi S. aureus hoc S. lugdunensis v nu kt qu khng, cc chng ny nn bo co l khng oxacillin. Xem lu (9).

Oxacillin i vi staphylococci coagulase m tnh tr S. lugdunensis.

1 g oxacillin

0.25 (oxacillin)

0.5 (oxacillin)

M100-S21 i vi staphylococci coagulase m tnh tr S. lugdunensis (14) Tiu chun din gii kt qu ca oxacillin c th ch l khng i vi mt s staphylococci coagulase m tnh bi v mt s chng staphylococci coagulase m tnh (tr S. epidermidis) c gi tr MIC oxacillin t 0.52 g/mL mc d chng thiu mecA. i vi cc trng hp nhim khun nng do staphylococci coagulase m tnh khng phi S. epidermidis xt nghim mecA hoc PBP 2a hoc khng sinh vi khoanh giy cefoxitin c th thch hp vi cc chng c gi tr MIC t 0.5 n 2 g/mL.

30 g cefoxitin

25

24

Xem lu (12) Xem lu (9)

Ampicillin

10g

29

28

0.25

0.5

(15) i din cho nhm Ampicillin and

M100-S21 Amoxicillin. (16) i vi chng staphylococci khng oxacillin, bo co v tnh khng hoc khng bo co. O Methicillin 5g 14 10-13 9 8 2 16 4 (17) Ch cho vi S. aureus. Xem lu (17).

O Nafcillin 1g 13 11-12 10 PHI HP KHANG SINH -LACTAM V CHT C CH -LACTAMASE

(18) i vi cc chng staphylococci khng oxacillin, bo co v tnh khng hoc khng bo co Xem lu (4) v (9). O O O O Amoxicillin-clavulanic axit Ampicillin-sulbactam Piperacillin-tazobactam 100/10 g

20/10 g 10/10 g

20 15 18

12-14 -

19 11 17

4/2 8/4 8/4

16/8

8/4 32/16 16/4

Ticarcillin-clavulanic 23 axit 75/10 g 22 8/2 16/2 CEPHEMS (NG TIM) (Bao gm cephalosporins th h I, II, III, v IV. Tham kho bng ch thch I.) Xem lu (18). Xem lu (4) v (9). O Cefamandole O Cefazolin O Cefepime O Cefmetazole O Cefonicid O Cefoperazone O Cefotaxime O Cefotetan

30 g 30 g 30 g 30 g 30 g 30 g 30 g 30 g

18 18 18 16 18 21 23 16

15-17 15-17 15-17 13-15 15-17 16-20 15-22 13-15

14 14 14 12 14 15 14 12

8 8 8 16 8 16 8 16

16 16 16 32 16 32 1632 32

32 32 32 64 32 64 64 64

M100-S21 O Ceftazidime O Ceftizoxime O Ceftriaxone O Cefuroxime (tim) O Cephalothin O Moxalactam CEPHEMS (NG UNG) Xem lu (18). Xem lu (4) v (9). O Cefaclor O Cefdinir O Cefpodoxime O Cefprozil O Cefuroxime (ung) O Loracarbef CARBAPENEM Xem lu (18). Xem lu (4) v (9). O Ertapenem O Imipenem O Meropenem GLYCOPEPTIDES B Vancomycine 30 g 30 g 30 g 30 g 30 g 30 g 18 20 21 18 18 23 15-17 15-19 14-20 15-17 15-17 15-22 14 14 13 14 14 14 8 8 8 8 8 8 16 1632 1632 16 16 1632 32 64 64 32 32 64

30 g 5 g 10 g 30 g 30 g 30 g

18 20 21 18 23 18

15-17 17-19 18-20 15-17 15-22 15-17

14 16 17 14 14 14

8 1 2 8 4 8

16 2 4 16 816 16

32 4 8 32 32 32

10 g 10 g 10 g -

19 16 16 -

16-18 14-15 14-15 -

15 13 13 -

2 4 4 2

4 8 8 4-8

8 16 16 16 i vi S. aureus (19) Xt nghim MIC cn tin hnh khng nh tnh nhy cm ca cc chng staphylococci vi vancomycin. Phng php khoanh giy khuch tn khng phn bit c cc chng nhy cm vi vancomycin v cc chng khng trung gian vi khng sinh ny ng thi cng

M100-S21 khng phn bit c cc chng staphylococci coagulase m tnh nhy cm, khng v khng trung gian vi vancomycin, tt c cc chng ny s cho ng knh vng c ch tng t nhau. (20) Khoanh giy vancomycin 30-g pht hin cc chng S. aureus cha gene vanA khng vancomycin (VRSA). Cc chng ny th hin khng vng c ch xung quanh khoanh khng sinh (ng knh = 6 mm). Cc chng th hin khng vng c ch cn phi c nh danh li. Cc chng staphylococci c ng knh vng c ch ca vancomycin 7 mm khng nn bo co l nhy cm khi cha tin hnh MIC vancomycin. (21) Gi cc chng S. aureus c MIC vancomycin 8 g/mL n cc phng xt nghim k thut cao hn. Xem ph lc A (22) Khoanh giy khuch tan khng ng tin cy i

M100-S21 vi vancomycin. Tham kho Bng 2C-S4i vi S. aureus cui Bng 2C, Phn 12.1.3 ti liu M07A8, v Phn 11.1.3 ti liu M02-A10. B Vancomycin 4 816 32 i vi cc chng coagulase m tnh Xem lu (19) v (22). (23) Gi cc chng Staphylococcus coagulase m tnh c gi tr MIC 32 g/mL n phng xt nghim tiu chun cao hn. Xem ph lc A Xem Phn 12.1.3 ti liu M07-A8 v Phn 11.1.3 ti liu M02-A10. (24) Tiu chun c kt qu ca khoanh giy khuch tan ca Teicoplanin cha c nh gi li cng nh nh gi li tiu chun c kt qu khoanh giy khch tn ca vancomycin trong cc nghin cu gn y. Do , kh nng phn bit cc chng staphylococci khng v khng trung gian vi teicoplanin so vi cc chng nhy cm cha r.

Inv.

Teicoplanin

30 g

14

11-13

10

16

32

M100-S21 LIPOPEPTIDES B Daptomycin 1 (25) Khoanh giy khuch tan khng ng tin cy i vi daptomycin (26) Daptomycin khng c php bo co i vi nhng chng phn lp c t bnh phm ng h hp di. Xem lu (7).

AMINOGLYCOSIDES C Gentamicin 10 g 15 13-14 12 4 8 16 O Amikacin 30 g 17 15-16 14 16 32 64 O Kanamycin 30 g 18 14-17 13 16 32 64 O Netilmicin 30 g 15 13-14 12 8 16 32 O Tobramycin 10 g 15 13-14 12 4 8 16 MACROLIDE (27) Khng bo co thng qui vi cc chng phn lp t ng tit niu. A Azithromycin hoc 15 g 18 14-17 13 2 4 8 A clarithromycin hoc 15 g 18 14-17 13 2 4 8 A erythromycin 15 g 23 14-22 13 0.5 14 8 O Dirithromycin 15 g 19 16-18 15 2 4 8 KETOLIDES B Telithromycin 15 g 22 19-21 18 1 2 4 TETRACYCLIN (26) Cc chng nhy cm vi tetracycline cng c xem nh nhy cm vi doxycycline v minocycline. Tuy nhin, mt s chng khng trung gian hoc khng vi tetracycline vn c th nhy cm vi doxycycline v/hoc minocycline. B Tetracycline 30 g 19 15-18 14 4 8 16 B Doxycycline 30 g 16 13-15 12 4 8 16 O Minocycline 30 g 19 15-18 14 4 8 16 FLUOROQUINOLONES (27) Cc chng Staphylococcus spp. c th tr nn khng thuc trong qu trnh iu tr ko di vi khng sinh quinolones. Do , cc chng ny ban u c th nhy cm nhng sau 3-4 ngy iu tr tr nn khng thuc. m bo v tin cy nn tin hnh xt nghim lp li vi cc chng ny

M100-S21 C C C C U U O Ciprofloxacin hoc Levofloxacin hoc Ofloxacin Moxifloxacin Lomefloxacin Norfloxacin Enoxacin 5 g 5 g 5 g 5 g 10 g 10 g 10 g 21 19 18 24 22 17 18 16-20 16-18 15-17 21-23 19-21 13-16 15-17 15 15 14 20 18 12 14 1 1 1 0.5 2 4 2 2 2 2 1 4 8 4 4 4 4 2 8 16 8

(30) Khng sinh ny c FDA ph duyt dng trong iu tr S. saprophyticus v S. epidermidis (khng dng cho S. aureus).

O Gatifloxacin O Grepafloxacin O Sparfloxacin Inv. Fleroxacin NITROFURANTOINS U Nitrofurantoin LINCOSAMIDES A Clindamycin

5 g 5 g 5 g 5 g 300 g 2 g

23 18 19 19 17 21

20-22 15-17 16-18 16-18 15-16 15-20

19 14 15 15 14 14

0.5 1 0.5 2 32 0.5

1 2 1 4 64

2 4 2 8 128 4 (31) Khng clindamycin suy on c th c pht hin bng phng php khoanh giy khuch tn s dng vng D v bng phng php pha long s dng mt ging duy nht cha 2 khng sinh phi hp erythromycin v clindamycin. Tham kho Bng 2C-S4 v 2C-S5, Phn 12 ti liu M02-A10, v Phn 13 ti liu M07-A8 v cc khuyn co hin thi.

M100-S21 Xem lu (27). C CH CON NG CHUYN HO FOLATE A Trimethoprim/Sulfameth 1.25/23.75 oxazole g U Sulfonamides 250-300 g

16 17

11-15 13-16

10 12

2/38 256

4/76 512 (32) C th dng khoanh giy khng sinh sulfisoxazole i din cho cc khng sinh nhm sulfonamide ang c s dng hin thi.

U Trimethoprim PHENICOLS C Chloramphenicol ANSAMYCINS B Rifampin

5 g 30 g 5 g

16 18 20

11-15 13-17 17-19

10 12 16

8 8 1

16 2

16 32 4 Xem lu (27) (33) Rx: Rifampin khng nn s dng n c trong iu tr.

STREPTOGRAMINS C Quinupristin-dalfopristin

15 g

19

16-18

15

(34) Bo co i lp S. aureus nhy cm vi methicillin.

(35) Khi xt nghim vi linezolid, nn kim tra vng c ch bng nh sng xuyn qua. Cc chng cho kt qu khng nhy cm nn khng nh li bng phng php MIC. Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu, QC, m bo cht lng xt nghim; FDA,Cc qun l an ton thuc v thc phm; MRS,

OXAZOLIDINONES B Linezolid

30 g

21

20

M100-S21 Staphylococci khng methicillin; MOD-SA, t cu vng thay i:PBP, Protein gn penicillin; PCR, phn ng khuch i chui gen; VRSA, gen vanA khng vancomycin;

M100-S21 Bng b sung 2C-S4. Xt nghim sng lc cc chng sinh -Lactamase, khng oxacillin, khng oxacillin qua trung gian mecA bng cefoxitin, vancomycin MIC 8 g/mL, khng clindamycin do kch thch v khng mupirocin mc cao ca cc chng Staphylococcus aureus trong Bng 2C Xt nghim -Lactamase Khng Khng oxacillin qua Vancomycin Khng clindamycin do kch Khng Mupirocin mc cao a,b, sng lc Oxacillin trung gian mecA s MIC thch dng Cefoxitin 8 g/mL S. aureus v S. S. aureus S. aureus v S. aureus S. aureus v S. lugdunensis S. aureus Nhm vi lugdunensis vi S. lugdunensis Khng vi erythromycin v nhy khun MIC penicillin cm hoc khng trung gian vi 0.12 g/mL clindamycin hoc ng knh vng c ch 29 mm Xt nghim da Pha long Khoanh Vi pha long Pha long Khoanh giy Vi pha long trn Khoanh Vi pha Phng trn Nitrocefin trn thch giy trong canh trn thch khuch tn thch giy long php xt khuch thang khuch tn trong nghim tn canh thang MHA vi 4% MHA CAMHB Thch no MHA hoc MHA CAMHB CAMHB Mi trng NA NaCl tim (BHI) thch mu s dng cho MIC NA Oxacillin 6 Khoanh cefoxitin 4 vancomycin Khoanh giy erythromycin Khoanh Ging Nng g/mL giy g/mL 6 g/mL erythromycin 4 g/mL v 0.5 khng sinh cha khng sinh cefoxitin 15-g v g/mL mupirocin mupiroci 30 g khoanh giy clindamycin trong 200-g n clindamycin cng mt ging 2562-g t cch g/mL nhau 1526 mm Pht trin th Pha huyn Cc Phng php Pha huyn Cc phng Phng php vi Cc Phng Huyn dch pht (v d, ly dch vi khun phng vi pha long dch vi php khoanh pha long chun phng php vi vi khun khun lc t trc tip t php chun c khun trc giy khuch c khuyn co php pha long vng xung khun lc t khoanh khuyn co tip t khun tn chun khoanh chun quanh khoanh c tng giy lc t c khuyn giy c

khng sinh oxacillin hoc cefoxitin trn mi trng thch mu hoc MHA sau 1618h nui cy)

ng c chun 0.5 McFarland. S dng que cy c vng cy 1-L hoc tm bng cy ria trn a mt vng c ng knh 10-15mm hoc a thch

khuch tn chun c khuyn co

iu kin nui cy

Nhit phng

3335 C; Hiu kh. (Nui cy nhit trn 35 C C th khng pht hin c MRSA.)

Thi gian nui cy

Ti a 1h i vi xt nghim da trn nitrocefin hoc

24h; c vi nh sng xuyn qua

3335 C; Hiu kh. (Nui cy nhit trn 35 C C th khng pht hin c MRSA.) 16-18h

3335 C; Hiu kh. (Nui cy nhit trn 35 C C th khng pht hin c MRSA.)

c tng ng c chun 0.5 McFarland. S dng que cy c vng cy 1-L hoc tm bng cy ria trn a mt vng c ng knh 10-15mm hoc a thch 352 C; Hiu kh.

co Hoc Vng cy dy trn a thch

M100-S21 khuch tn khuyn co chun c khuyn co

352 C; Hiu kh.

352 C; Hiu kh.

352 C; Hiu kh.

352 C; Hiu kh.

16-20h

24h; c vi nh sng xuyn qua

16-18h

18-24h

24h; c vi nh sng xuyn qua

24h; c vi nh sng xuyn

Phng php xt nghim Kt qu

theo hng dn ca nh sn xut Xt nghim da trn Nitrocefin Xt nghim Nitrocefin: chuyn t mu vng sang /hng=lactamase dng tnh

M100-S21 qua

Pha long trn thch Kim tra cn thn vi nh sng xuyn qua pht hin >1 khun lc hoc khun lc to thnh mt lp mng kh pht hin > 1 khun lc = khng oxacillin

Khng sinh 21 mm = mecA dng tnh 22 mm = mecA m tnh

Vi pha long

Pha long trn thch Kim tra cn thn vi nh sng xuyn qua pht hin >1 khun lc hoc khun lc to thnh mt lp mng kh pht hin > 1 khun lc = gim nhy cm vi vancomycin

Khng sinh Nu xut hin vng c ch c hnh dng khng trn bn cnh khoanh erythromycin (vng ch D)=khng clindamycin do kch thch Khun lc pht trin nh trong vng c ch xung quanh khoanh giy clindamycin= khng clindamycin ( sn c) k c khi khng xut hin vng D

Vi pha long

Khng sinh Vi pha long Kim tra cn thn bng nh sng xuyn qua pht hin s pht trin yu trong vng c ch Khng c vng c ch=khng mupirocin mc cao C vng c ch = khng c s khng mupirocin mc cao Bo co cc chng khng c vng c i vi ging 256g/mL Pht trin= khng mupiroci n mc cao Khng pht trin= khng khng mupiroci n mc cao

>4 g/mL = mecA dng tnh 4 g/mL = mecA m tnh

Bt k s pht trin no=khng clindamycin do kch thch Khng pht trin=khng khng clindamycin do kch thch

Xt nghim thm v bo co

Cc chng staphylococci Lactamase dng tnh th

Cc chng staphylococci khng oxacillin th

Cefoxitin c dng lm i din cho xt nghim c ch khng qua trung gian mecA.

Tin hnh MIC cho vancomycin i vi cc

Bo co cc chng khng clindamycin do kch thch vi dng lu khng clindamycin

Nu c s pht trin trong ging

khng vi penicillin, amino-, carboxy- v ureidopenicillin.

khng vi tt c cc khng sinh nhm Lactam; cc khng sinh nhm Lactam nn c bo co kt qu khng hoc khng bo co.

Cc chng mecA dng tnh nn c bo co l khng oxacillin (khng phi cefoxitin); cc khng sinh nhm -Lactam nn c bo co kt qu khng hoc khng bo co. Bi v cc c ch khng oxacillin khc thng him gp hn mecA, cc chng mc d mecA m tnh nhng MIC oxacillin nm trong gii hn khng (MIC 4 g/mL) nn c bo co l khng oxacillin

Phng php xt nghim

Xt nghim da trn Nitrocefin

Pha long trn thch

Khoanh giy khuch tn

Vi pha long

chng S. aureus pht trin trn mi trng sng lc BHIvancomycin bng cc phng php pht hin MIC c gi tr. Xt nghim trn mi trng sng lc khng ng tin cy pht hin tt c cc chng S. aureus khng trung gian vi vancomycin. MICs bng 4 g/mL s khng pht trin. Pha long trn thch

Ghi ch Chng ny c cho l khng clindamycin da trn s pht hin khng clindamycin do kch thch. Clindamycin c th vn c hiu qu trn lm sng mt s bnh nhn

M100-S21 ch l nng khng 256mupirocin g/mL th mc bo co cao. khng mupiroci Nu c n mc vng c cao. ch, bo co khng Nu c s khng c khng s pht mupirocin trin mc trong cao tup nng 256g/mL th bo co khng c s khng mupiroci n mc cao.

Khoanh giy khuch tn

Vi pha long

Khoanh giy khuch tn

Vi pha long

 xut kim sot cht lng

S. aureus ATCC 29213 dng tnh S. aureus ATCC 25923 m tnh (hoc xem hng dn ca nh sn xut)

S. aureus ATCC 29213 Nhy cm S. aureus ATCC 43300 Khng

S. aureus ATCC 25923 mecA m tnh (vng c ch 23-29 mm) S. aureus ATCC 43300 mecA Dng tnh (vng c ch 21 mm)

S. aureus ATCC 29213 mecA m tnh (MIC 14g/mL) S. aureus ATCC 43300 mecA dng tnh (MIC >4 g/mL)

Enterococcu s faecalis ATCC 29212 Nhy cm E. faecalis ATCC 51299 Khng

S. aureus ATCC 25923 i vi QC khoanh giy khng sinh thng qui; Xem Bng 3A v cc chng QC

S. aureus ATCC BAA976 hoc S. aureus ATCC 29213 Khng pht trin S. aureus ATCC BAA977 pht trin

S. aureus ATCC 25923 (khoanh giy 200g) mupA m tnh (vng c ch 29- 38 mm) S. aureus ATCC BAA1708 mupA Dng tnh (khng c vng c ch)

M100-S21 S. aureus ATCC 29213 mupA m tnh (MIC 0.06 0.5 g/mL) E. faecalis ATCC 29212 mupA m tnh (MIC 16 n 128g/m L) S. aureus ATCC BAA170 8 mupA Dng tnh (pht trin ging 256g/ml

M100-S21 Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu, QC, m bo cht lng xt nghim; FDA,Cc qun l an ton thuc v thc phm; MRS, Staphylococci khng methicillin; Lu a. Mc d khng c nh gi mt cch chnh thc bng nhng phn tch da trn ti liu CLSI M23, mt s nghin cu ch ra mi lin kt gia s thiu p ng ca cc phc iu tr da trn mupirocin n c vi cc chng c gi tr MICs 512. Mc d ti liu ny khng cung cp hng dn v tiu chun din gii kt qu i vi mupirocin, khoanh giy khuch tn v th nghim sng lc MIC c m t y xc nh i vi nhng chngr m mupirocin MIC l 512 g/mL. b. Ti liu tham kho: Simor AE. Randomized controlled trial of chlorhexidine gluconate for washing intranasal mupirocin, and rifampin and doxycycline versus no treatment for the eradication of methicillin-resistant Staphylococcus aureus colonization. Clin Infect Dis. 2007; 44: 178-185; Harbarth S, Dharan S, Liassine N, Herrault P, Auckenthaler R, Pittet D. Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1999; 43:1412-1416; v Walker ES, Vasquez JE, Dula R, Bullock H, Sarubbi FA. Mupirocin-resistant, methicillin-resistant Staphylococcus aureus; does mupirocin remain effective? Infect Control Hosp Epidemiol. 2003;24:342-346.

M100-S21 Bng 2C-S5. Xt nghim sng lc xc nh tnh khng do -Lactamase, khng Oxacillin qua trung gian mecA s dng Cefoxitin, v khng Clindamycin do kch thch cc chng Staphylococci khng sinh Coagulase (tr Staphylococcus lugdunensis) i vi cc trng hp trong Bng 2C Xt nghim sng lc Nhm vi khun -Lactamase Staphylococcia khng sinh coagulase vi MICs ca penicillin 0.12 g/mL hoc ng knh vng c ch 29 mm Xt nghim da trn Nitrocefin NA Khng Oxacillin qua trung Khng Clindamycin do kch thch (inducible) gian mecA s dng Cefoxitin Staphylococcia khng sinh Staphylococcia khng sinh coagulase khng vi coagulase erythromycin v nhy cm hoc khng trung gian vi clindamycin. Khoanh giy khuch tn MHA Khoanh giy khuch tn MHA hoc a thch mu s dng cho xt nghim MIC Khoanh giy erythromycin 15-g v clindamycin 2-g t cch nhau 1526 mm Thao tc khoanh giy khuch tn chun Hoc Vng c cy m c trn a 35 2 C; hiu kh Vi pha long canh thang CAMHBb

Phng php xt nghim Mi trng

Nng khng sinh Huyn dch vi khun

NA

Khoanh giy cefoxitin 30-g

Erythromycin 4 g/mL v clindamycin 0.5 g/mL trong cng mt ging Thao tc vi pha long canh thang chun

iu kin nui cy

Pht trin th pht (v d, khun lc ranh gii vng c ch xung quanh khoanh giy oxacillin hoc cefoxitin trn mi trng MHA hoc thch mu sau 16-18h nui cy) Nhit phng

Thao tc khoanh giy khuch tn chun

3335 C; hiu kh (Xt nghim nhit phng cao hn 35 C c th khng pht hin MRS.) 24h (c th bo co kt qu sau 18h nu khng) 24 mm = mecA dng tnh; 25 mm = mecA m tnh.

35 2 C; hiu kh

Thi gian nui cy

Kt qu

Ti a 1h i vi xt nghim da trn nitrocefin hoc tun th hng dn ca nh sn xut Xt nghim da trn Nitrocefin: i t mu vng sang /hng= lactamase dng tnh

16-18h

18-24h

Nu xut hin vng c ch c hnh dng khng trn bn cnh khoanh erythromycin (vng ch

Bt k s pht trin no=khng clindamycin do kch thch

Phng php xt nghim

Xt nghim da trn Nitrocefin

Khoanh giy khuch tn

D)=khng clindamycin do kch thch Khun lc pht trin nh trong vng c ch xung quanh khoanh giy clindamycin=khng clindamycin ( sn c) k c khi khng xut hin vng D Khoanh giy khuch tn

M100-S21 Khng pht trin=khng khng clindamycin do kch thch

Vi pha long canh thang

Xt nghim thm v Cc chng staphylococci sinh lactamase khng vi penicillin, bo co amino-, carboxy- v Ureidopenicillins.

Cefoxitin c s dng i din cho khng oxacillin qua trung gian mecA. Cc chng mecA dng tnh bo co kt qu khng oxacillin (khng phi cefoxitin); cc khng sinh nhm -lactam khc nn c bo co l khng hoc khng bo co. Bi v s him gp ca cc c ch khng khc khng phi qua trung gian mecA, cc chng mecA m tnh nhng gi tr MIC l khng (MICs 4 g/mL) nn c bo co l khng oxacillin. i vi cc trng hp nhim khun nng do staphylococci khng sinh coagulase khng phi S. epidermidis, xt nghim chn

Bo co cc chng khng clindamycin do kch thch vi dng lu khng clindamycin Ghi ch Chng ny c cho l khng clindamycin da trn s pht hin khng clindamycin do kch thch. Clindamycin c th vn c hiu qu trn lm sng mt s bnh nhn

M100-S21 on mecA hoc protein biu hin bi mecA c th p dng cho cc chng c gi tr MIC ca oxacillin l 0.5 n 2 g/mL. S. aureus ATCC 25923 mecA m tnh (ng knh vng c ch 2329 mm)

xut QC

S. aureus ATCC 29213 dng tnh S. aureus ATCC 25923 m tnh (hoc tham kho cc xut ca nh sn xut)

S. aureus ATCC 25923 i vi QC thng qui khoanh giy khng sinh; Xem Bng 3A i vi cc chng QC b sung.

S. aureus ATCC BAA-976 hoc S. aureus ATCC 29213 khng pht trin

S. aureus ATCC S. aureus ATCC 43300 mecA dng tnh BAA-977 pht trin (ng knh vng c ch 21 mm) Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu, QC, m bo cht lng xt nghim; FDA,Cc qun l an ton thuc v thc phm;

Lu a. Tr S. lugdunensis, c bao gm trong nhm S. aureus. Xem bng trc.

M100-S21 Bng 2D. Tiu chun din gii kt qu ng knh vng c ch v nng c ch ti thiu(MIC)vi Enterococcus spp. iu kin th nghim Mi trng: Khoanh giy khuch tn: MHA Canh thang pha long: CAMHA; CAMHB b sung 50 g/mL calcium i vi daptomycin\ Pha long trn thch: MHA; pha long trn thch cha c nh gi vi daptomycin Phng php tng sinh bng canh thang hoc pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352oC, hiu kh, 16-18h; Khoanh giy khuch tn: 16-18h Cc phng php pha long: 16-20h Tt c cc phng php: 24h i vi vancomycin Cc xut kim sot cht lng ti thiu (Xem bng 3 v 4: gii hn QC cho php) Khoanh giy khuch tn: Staphylococcus aureus ATCC 25923 Cc phng php pha long: Enterococcus faecalis ATCC 29212

Huyn dch vi khun:

iu kin nui cy:

Tham kho Bng 2D-S6 cui Bng 2D i vi cc xut b sung v iu kin xt nghim, bo co v QC.

Lu chung (1) i vi phng php khoanh giy khuch tn, o ng knh vng c ch (xc nh bng mt thng mp), bao gm c ng knh ca khoanh giy khng sinh. Soi a trn nn en bng nh sng phn chiu ngoi tr i vi vancomycin, nn c a bng nh sng xuyn qua (cm a trc n chiu). Vng c ch l vng trong bng mt thng khng quan st thy s pht trin ca vi khun. Khng n s pht trin yu ca cc khun lc nh li ti m ch c th quan st bng knh hin vi xung quanh mp ca vng c ch. Nu trong vng c ch c th quan st thy s pht trin ca vi khun, chng t trng hp vi khun khng vancomycin. (2) CNH BO: i vi Enterococcus spp., cephalosporins, aminoglycosides (tr trng hp khng mc cao), clindamycin, v trimethoprimsulfamethoxazole c th c tc dng trn in vitro, nhng khng c hiu qu trn lm sng v do khng c bo co v tnh nhy cm.

M100-S21 (3) Hip ng gia ampicillin, penicillin, hoc vancomycin v mt khng sinh nhm aminoglycoside c th c d on cho Enterococci bng cch s dng xt nghim sng lc i vi s khng khng sinh nhm aminoglycoside mc cao (gentamicin v streptomycin). Cc khng sinh aminoglycosides khc khng cn th, v tc dng khng khun ca chng i vi Enterococci khng kh hn gentamicin v streptomycin. (4) i vi mt s cp vi khun/khng sinh, hin tng khng hoc him khi pht hin chng khng khng cho php xc nh bt k mt kt qu no ngoi nhy cm. i vi cc chng cho kt qu khng nhy cm, ton b qu trinh phn lp nh danh v tin hnh th nghim nhy cm khng sinh cn c lm li. (Xem ph lc A). LU : Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc

M100-S21 Bng 2D. (Tip) Nhm th nghim/ Khng sinh bo co PENICILLINS A Penicillin A Ampicillin Hm lng 10 v 10 g Gii hn ng knh vng c ch (mm) S I R 15 17 14 16 Tiu chun din gii kt qu MIC (g/mL) S I R 8 8 16 16 Lu

(5) Ampicillin l i din cho ampicillin v amoxicillin. Cc kt qu th nghim vi ampicillin c th c dng d on tnh nhy cm i vi amoxicillin-axit clavulanic, ampicillin-sulbactam, piperacillin, v piperacillin-tazobactam ca cc chng Enterococci khng sinh -lactamase. Tnh nhy cm vi ampicillin c th c s dng d on tnh nhy cm vi imipenem, vi cc chng c khng nh l E. faecalis. (6) Enterococci nhy cm vi penicillin th cng c th d on l nhy cm vi ampicillin, amoxicillin, ampicillin-sulbactam, amoxicillinclavulanate, piperacillin, v piperacillin-tazobactam i vi cc chng Enterococci khng sinh men lactamase. Tuy nhin, Enterococci nhy cm vi ampicillin th khng th suy ra nhy cm vi penicillin. Nu cn kt qu vi penicillin th cn tin hnh th nghim. (7) Rx: Liu php kt hp gia ampicillin, penicillin, hoc vancomycin (i vi cc chng nhy cm), v mt khng sinh nhm aminoglycoside, thng dng cho cc

M100-S21 trng hp nhim khun do enterococcus (cu khun ng rut) nng, nh vim mng trong tim, tr trng hp khng mc cao vi c gentamicin v streptomycin, phi hp ny c tc dng d bo tc dng hip ng dit Enterococcus. (8) Cc chng Enterococci khng ampicillin hoc penicillin do c ch sinh men -lactamase rt t c bo co. Pht hin khng ampicillin hoc penicillin do c ch sinh men lactamase bng phng php khoanh giy khuch tn thng qui hoc phng php pha long khng ng tin cy, nhng c pht hin bng th nghim trc tip, th nghim lactamase da trn nitrocefin. Bi v cc chng Enterococci -lactamase dng tnh rt t, xt nghim ny khng cn tin hnh thng qui, m ch p dng vi cc trng hp c la chn. Nu kt qu th nghim lactamase dng tnh cho php d on v tnh khng vi penicillin, amino-, carboxy-, v ureidopenicillins (xem Ph lc I). GLYCOPEPTIDS B Vancomycin 30 g 17 15-16 14 4 8-16 32 (9) Khi th nghim tnh nhy cm vi vancomycin ca cc chng Enterococci, qu trnh nui cy nn gi trong vng 24h pht hin tnh trng khng mt cch chnh xc. Cc chng cho kt qu MIC t 8-16 g/ml, tin hnh cc xt nghim sinh

M100-S21 vt ha hc nh danh li nh i trng hp Khng Vancomycin trong Bng b sung 2D-S6, cui Bng 2D. o ng knh vng c ch di nh sng xuyn qua, nu c bt k khun lc no trong vng c ch chng t c s khng vancomycin. Cc chng cho kt qu khng trung gian cn c xt nghim bng phng php MIC nh m t trong ti liu M07-A8. Tham kho xt nghim Khng Vancomycin c m t trong Bng b sung 2D-S6 cui Bng 2D. Xem lu (3) v (7). Inv. Teicoplanin LIPOPEPTIDES B Daptomycine 30 g 14 11-13 10 8 4 16 32 (10) Khoanh giy khuch tn khng nh tin cy i vi daptomycin. (11) Khng bo co thng qui vi cc chng phn lp t bnh phm ng h hp di. Xem lu (4) (12) Khng bo co thng qui vi cc chng phn lp t nc tiu.

MACROLIDES O Erythromycin

15 g

23

14-22

13

0.5

1-4

TETRACYCLINES (13) Cc chng vi khun nhy cm vi tetracycline cng c th xem nh nhy cm vi doxycycline v minocycline. Tuy nhin, mt s chng khng hoc khng trung gian vi tetracycline c th vn nhy cm vi doxycycline v/hoc minocycline. U Tetracycline 30 g 19 15-18 14 4 8 16 O O Doxycycline Minocycline 30 g 30 g 5 g 16 19 21 13-15 15-18 16-20 12 14 15 4 4 1 8 8 2 16 16 4

FLUOROQUINOLONES U Ciprofloxacin

M100-S21 U U O Levofloxacin Norfloxacin Gatifloxacin 5 g 10 g 5 g 17 17 18 14-16 13-16 1517 13 12 14 2 4 2 4 8 4 8 16 8

(14) Tiu chun din gii kt qu ch p dng cho cc chng phn lp t ng niu

NITROFURANS U Nitrofurantoin ANSAMYCINS O Rifampin FOSFOMYCINS O Fosfomycin

300 g 5 g

17 20

1516 17-19

14 16

32 1

64 2

128 4 (15) Rx: Rifampin khng nn s dng trong liu php n (16) Ch nh i vi cc chng E. faecalis phn lp t ng tit niu. (17) S dng phng php pha long trn thch xc nh MIC. Mi trng thch nn b sung vi 25 g/mL of glucose-6-phosphate. Khng nn tin hnh phng php pha long trong canh thang. (18) Khoanh khng sinh fosfomycin hm lng 200-g cha 50 g glucose-6-phosphate.

200 g

16

1315

12

64

128

256

PHENICOLS C Chloramphenicol STREPTOGRAMINS B Quinupristindalfopristin OXAZOLIDINONES B Linezolid

30 g 15 g

18 19

1317 16-18

12 15

8 1

16 2

32 4

Xem lu (12) (19) Ch bo co i vi E. faecalis khng vancomycin.

30 g

23

21-22

20

M100-S21 Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu;

M100-S21 Bng b sung 2D-S5. Cc xt nghim sng lc cc chng Enterococcus spp. khng Aminoglycoside mc cao (HLAR) v khng Vancomycin i vi cc trng hp trong Bng 2D Xt nghim sng lc Phng php xt nghim Mi trng Nng khng sinh Huyn dch vi khun Gentamicin HLAR Khoanh giy khuch tn MHA Khoanh giy gentamicin 120 g xut phng php khoanh giy khuch tn chun Pha long canh thang Canh thang BHIa Gentamicin 500 g/ml xut phng php canh thang pha long chun Pha long trn thch Thch BHIa Gentamicin 500 g/ml Khoanh giy khuch tn MHA Khoanh giy streptomycin 300 g xut phng php khoanh giy khuch tn chun Streptomicin HLAR Pha long canh thang Canh thang BHIa Streptomycin 1000 g/ml xut phng php canh thang pha long chun 35 2 C; hiu kh 24-48h (nu quan st thy nhy cm 24h, li) Bt k khun lc no = khng Pha long trn thch Thch BHIa Streptomycin 2000 g/ml 10 L ca huyn dch vi khun m 0.5 McFarland tri trn b mt thch 35 2 C; hiu kh 24-48h (nu quan st thy nhy cm 24h, li) >1 khun lc = khng Khng Vancomycin Pha long trn thch Thch BHIa Vancomycin, 6 g/mL 110 L ca huyn dch vi khun m 0.5 McFarland tri trn b mt thch

iu kin nui cy Thi gian nui cy

35 2 C; hiu kh 16-18h

35 2 C; hiu kh 24h

10 L ca huyn dch vi khun m 0.5 McFarland tri trn b mt thch 35 2 C; 35 2 C; hiu hiu kh kh 24h 16-18h

35 2 C; hiu kh 24h

Kt qu

6 mm = Khng 79 mm = Khng kt lun c; 10 mm = Nhy cm.

Bt k mt khun lc no = khng

>1 khun lc = khng

6 mm=khng; 7-9 mm=khng kt lun; 10 mm = Nhy cm MIC tng quan: R = >1000 g/mL (canh thang) v >2000

>1 khun lc = khng vancomycin (kt lun s b)

MIC tng quan:

M100-S21 R = >500 g/mL S = 500 g/mL g/mL (thch);

Xt nghim thm v bo co

S = 500 g/mL (canh thang) v 1000 g/mL (thch) Khng: khng c tc dng hip ng vi cc khng sinh c tc dng ln thnh t bo (v d, ampicillin, penicillin, v vancomycin). Nhy cm: c tc dng hip ng vi cc khng sinh c tc dng ln thnh t bo (v d, ampicillin, penicillin, v vancomycin) v cng cho kt qu nhy cm. Nu kt khoanh giy khuch tn vn cha kt lun c: Tin hnh phng php pha long canh thang hoc trn thch khng nh.

Tin hnh xt nghim MIC ca vancomycin v th tnh di ng, sinh sc t phn bit cc chng khng thuc thu c theo c chVan A v VanB vi cc chng khng trung gian vi vancomycin theo c chVanC, v d, Enterococcus gallinarum v Enterococcus casseliflavus, l cc chng thng pht trin trn thch sng lc c vancomycin. Ngc li vi cc enterococci nh, E. casseliflavus v E. gallinarum vi gi tr MIC vancomycin 816 g/mL (trung gian) khc vi Enterococci khng vancomycin (VRE) i vi mc ch kim sot nhim khun. E. faecalis ATCC29212 Nhy

Cc xut QC

E. faecalis ATCC29212;

E. faecalis ATCC29212

E. faecalis ATCC29212

E. faecalis ATCC29212;

E. faecalis ATCC29212

E. faecalis ATCC29212

M100-S21 1623 mm Nhy cm E. faecalis ATCC51299 Khng Nhy cm E. faecalis ATCC51299 Khng 1420 mm Nhy cm E. faecalis ATCC51299 Khng Nhy cm E. faecalis ATCC51299 Khng cm E. faecalis ATCC51299 Khng

Lu
a

BHI = Canh thang no tim; mc d khng sn nhng ti u hn so vi mi trng thch hoc canh thang ng dextrose phosphate.

M100-S21 Bng 2E. Tiu chun c kt qu ng knh vng c ch v nng c ch ti thiu (MIC) i vi Haemophilus influenzae v H. parainfluenzae iu kin th nghim Mi trng: Khoanh giy khuch tn:Mi trng th Haemophillus (HTM) Pha long trn canh thang: canh thang HTM Pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352 oC, 5% CO2, 16-18h Khoanh giy khuch tn: 5% CO2; 16-18h Pha long trn canh thang: hiu kh; 20-24h Cc xut kim sot cht lng ti thiu (Xem bng 3A, 3B, 4A v 4B i vi gii hn QC cho php) Haemophilus influenzae ATCC 49247 Haemophilus influenzae ATCC 49766 Escherichia coli ATCC 35218 (khi th vi amoxicillinclavulanic axit)

Huyn dch vi khun:

iu kin nui cy:

Lu chung (1) (2) Heaemophilus spp., trong bng ny ch bao gm H. influenzae v H. parainfluenzae. Vi nhng loi khc thuc tc Haemophilus xem ti liu CLSI M45 bit v nhng th nghim v bo co khuyn co. i vi khoanh giy khuch tn, o ng knh vng c ch (v d, xc nh ranh gii vng c ch bng mt thng), bao gm ng knh khoanh giy. Soi a mi trng trn nn en vi nh sng phn chiu tr trng hp linezolid, oxacilin v vancomycin nn s dng nh sng xuyn qua. Xc nh ranh gii vng c ch bng mt thng, khng c s pht trin r rng ca vi khun. B qua s pht trin yu v cc khun lc nh li ti ch c th pht hin khi soi di knh lp hoc knh hin vi b ca vng c ch. i vi trimethoprim v sulfonamides, cc cht i khng trong mi trng c th cho php vi khun pht trin nh; do c th b qua s pht trin yu ny (khng qu 20%) v o ng knh vng c ch vi ranh gii xc nh bng mt thng. Ch cc kt qu th nghim vi ampicillin, mt trong s khng sinh cephalosporin th h 3, chloramphenicol, v meropenem nn c bo co thng qui vi cc chng Haemophilus influenzae phn lp t dch no ty.

(3)

(4)

(5)

(6)

M100-S21 Amoxicillin-clavulanic axit, azithromycin, clarithromycin, cefaclor, cefprozil, loracarbef, cefdinir, cefixime, cefpodoxime, cefuroxime, v telithromycin l cc khng sinh ng ung c th dng theo kinh nghim iu tr vim ng h hp Haemophilus spp. Kt qu th nghim tnh nhy cm vi cc khng sinh ny thng khng c ngha i vi tng bnh nhn c th. Tuy nhin cc kt qu ny c ngha i vi cc gim st v nghin cu dch t hc. Chun b mi trng HTM: chun b dung dch m hematin bng cch pha 50 mg bt hematin trong 100 mL dung dch NaOH 0.01 mol/L, un nng v khuy cho n khi tan hon ton. Sau , ly 30ml dung dch hematin cho vao 1L mi trng thch Mueller-Hinton vi 5g dch chit nm men. Sau khi hp tit trng v lm ngui, b sung thm 3 mL dung dch NAD (50 mg NAD ha tan trong 10 mL nc ct v trng, lc v trng), m bo v trng. i vi mt s cp khng sinh/vi khun, cc chng vi khun khng thuc him gp gy kh khn trong vic xc nh mc khng thuc khng gp hoc t l him gp cc chng khng thuc ngn cn vic xc nh cc kt qu ngoi trng hp nhy cm. i vi cc chng cho kt qu khng nhy cm, kt qu nh danh vi khun v xc nh mc nhy cm khng sinh cn c xc nh li. Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc

LU :

Bng 2E (Tip) Nhm th Khng sinh nghim/ bo co PENICILLINS A Ampicillin

Hm lng khoanh giy

ng knh vng c ch (mm) S I R 22 19-21 18

im gy MIC tng ng (g/mL) S I R 1 2 4

Lu

10 g

Xem lu (3) (7) Kt qu th nghim tnh nhy cm vi ampicillin nn dng suy ra tnh nhy cm vi amoxicillin. Trong hu ht cc trng hp, th nghim trc tip -lactamase c th pht hin nhanh s khng ampicillin v amoxicillin. Phn ln cc chng H. influenzae khng ampicillin v amoxicillin u sinh men -lactamase kiu TEM. Phn ln cc trng hp, xt nghim lactamase trc tip c th cho kt qu nhanh pht hin chng khng ampicillin v amoxicillin. (8) S t cc chng H. influenzae khng sinh -lactamase nhng khng

PHI HP -LACTAM/C CH -LACTAMASE B Ampicillin-sulbactam 10/10 g 20 C Amoxicillinclavulanic axit 20/10 g 20

19 19

2/1 4/2

M100-S21 ampicillin (BLNAR) c th khng vi amoxicillin-clavulanic axit, ampicillinsulbactam, cefaclor, cefetamet, cefonicid, cefprozil, cefuroxime, v loracarbef, mc d c th cho kt qu nhy cm in vitro. Xem lu (8) 4/2 Xem lu (8) 8/4 Xem lu (4) v (8)

Piperacillin100/10 g 21 1/4 tazobactam CEPHEMS (TIM) (Bao gm cephalosporins I, II, III, v IV. Tham kho Ch thch I) B Cefotaxime hoc 30 g 26 2 B Ceftazidime hoc 30 g 26 2 B Ceftriaxone 30 g 26 2 B Cefuroxime 30 g 20 17-19 16 4 O Cefonicid 30 g 20 17-19 16 4 O Cefamandole 4 O Cefepime 30 g 26 2 O Ceftizoxime 30 g 26 2 CEPHEMS (NG UNG) C Cefaclor 30 g 20 17-19 16 8 C Cefprozil 30 g 18 15-17 14 8 C Cefdinir hoc 5 g 20 1 C Cefixime hoc 5 g 21 1 C Cefpodoxime 10 g 21 2 C Cefuroxime 30 g 20 17-19 16 4 O Loracarbef 30 g 19 16-18 15 8 O Ceftibuten 30 g 28 2 Inv. Cefetamet 10 g 18 15-17 14 4 MONOBACTAMS C Aztreonam 30 g 26 2

2/4

Xem lu (8) Xem lu (8) Xem lu (3) v (6)

8 8 8 16 16 8 16 8 -

16 16 16 32 32 16 32 16 -

Xem lu (8) Xem lu (8) Xem lu (8) Xem lu (6) Xem lu (6)

Xem lu (4) v (6)

Xem lu (4) v (8) Xem lu (6) Xem lu (8) Xem lu (6)

M100-S21 CARBAPENEMS B Meropenem C Ertapenem hoc C Imipenem MACROLIDES C Azithromycin C Clarithromycin KETOLIDES C Telithromycin TETRACYCLINES C Tetracycline 10 g 10 g 10 g 15 g 15 g 15 g 30 g 20 19 16 12 13 15 29 11-12 12-14 26-28 10 11 25 0.5 0.5 4 4 8 4 2 16 8 4 32 16 8 Xem lu (3) v (6) Xem lu (6)

Xem lu (6)

Xem lu (4) (9) Cc chng nhy cm vi tetracycline th c th xem nh nhy cm vi doxycycline v minocycline

FLUOROQUINOLONES C Ciprofloxacin hoc 5 g C levofloxacin hoc 5 g C lomefloxacin hoc 10 g C moxifloxacin hoc 5 g C ofloxacin 5 g Gemifloxacin 5 g O Gatifloxacin 5 g O Grepafloxacin 5 g O Sparfloxacin O Trovafloxacin 10 g Inv. Fleroxacin 5 g C CH CON NG FOLATE A Trimethoprim1.25/23.75 sulfamethoxazole g PHENICOLS O Chloramphenicol 30 g

21 17 22 18 16 18 18 24 22 19 16

11-15

10

1 2 2 1 2 0.12 1 0.5 0.25 1 2 0.5/9.5 2

1/19 2/38 4

4/76

29

26-28

25

Xem lu (3) (10) Khng bo co thng qui cc chng phn lp t nc tiu (11) Rx: Rifampin khng nn s dng trong liu php n

ANASAMYCINS C Rifampin

5 g

20

17-19

16

M100-S21 Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; BLNAR -lactamase m tnh, khng ampicillin HTM, mi trng th nghim Haemophilus; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu, NAD, nicotinamide adenine dinucleotide; QC, m bo cht lng xt nghim;

Bng 2F. Tiu chun c kt qu ng knh vng c ch v nng c ch ti thiu (MIC) i vi Neisseria gonorrhoeae iu kin th nghim Mi trng: Khoanh giy khuch tn: Mi trng thch GC (c bn (thch chocolate c bn) v 1% yu t kch thch tng trng thch hp. Khng yu cu s dng yu t kch thch tng trng cysteine twj do cho phng php khoanh giy khuch tn Pha long trn thch: Mi trng thch GC c bn v 1% yu t kch thch tng trng thch hp. Yu cu s dng yu t kch thch tng trng cysteine t do i vi phng php pha long trn thch ca carbapenems v clavulanate. Yu t kch thch tng trng cha cysteine khng thay i cc kt qu ca cc khng sinh khc khi s dng xt nghim pha long. Pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 361 oC (khng vt qu 37 oC), 5% CO2, tt c cc phng php, 20-24h Cc xut kim sot cht lng ti thiu (Xem bng 3B v 4C i vi gii hn QC cho php) Neisseria gonorrhoeae ATCC 49226

Huyn dch vi khun: iu kin nui cy:

Lu chung (1) i vi khoanh giy khuch tn, o ng knh vng c ch (v d, xc nh ranh gii vng c ch bng mt thng), bao gm ng knh khoanh giy. Soi a mi trng trn nn en vi nh sng phn chiu tr trng hp linezolid, oxacilin v vancomycin nn s dng nh sng xuyn qua. Xc nh ranh gii vng c ch bng mt thng, khng c s pht trin r rng ca vi khun. B qua s pht trin yu v cc khun lc nh li ti ch c th pht hin khi soi di knh lp hoc knh hin vi b ca vng c ch. Hiu qu lm sng ca cefmetazole, cefotetan, cefoxitin, v spectinomycin trong iu tr cc chng cho kt qu khng trung gian vi cc khng sinh ny hin cha r. Th nghim khoanh giy khuch tn i vi N. gonorrhoeae, kt qu khng trung gian vi mt khng sinh no chng t hoc k thut c vn v cn lp li th nghim hoc thiu kinh nghim lm sng trong iu tr cc chng vi khun vi cc vng c ch ny. L do sau thng gp cc trng

(2) (3)

M100-S21 hp i vi cefmetazole, cefotetan, cefoxitin, v spectinomycin. Cc chng khng trung gian vi cc loi khng sinh khc c t l c kh nng iu tr lm sng c ghi nhn thp hn (85 to 95%) so vi cc chng nhy cm c t l l >95%. (4) Mi trng s dng cho N. gonorrhoeae bao gm thch GC (thch chocolate c bn) b sung thm 1% yu t thch tng trng thch hp (1.1 g Lcysteine, 0.03 g guanine HCL, 3 mg thiamine HCL, 13 mg PABA, 0.01 g B12, 0.1 g cocarboxylase, 0.25 g NAD, 1 g adenine, 10 g L-glutamine, 100 g glucose, 0.02 g ferric nitrate [trong 1 L H2O]) c b sung sau khi hp tit trng. i vi mt s cp vi khun/khng sinh, hin tng khng hoc him khi pht hin chng khng khng cho php xc nh bt k mt kt qu no ngoi nhy cm. i vi cc chng cho kt qu khng nhy cm, ton b qu trinh phn lp nh danh v tin hnh th nghim nhy cm khng sinh cn c lm li (Xem Ph lc A). LU : Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc

(5)

M100-S21

Bng 2F. Nhm th Khng sinh nghim/ bo co PENICILLINS C Penicillin

Hm lng

ng knh vng c ch (mm) S I R 47 27-46 26

Tiu chun din gii kt qu MIC(g/mL) S I R 0.06 0.12-1 2 Xem lu (3)

Lu

10 UI

(6) Th nghim dng tnh vi lactamase chng t chng khng vi penicillin, ampicillin, and amoxicillin. (7) Th nghim -lactamase s pht hin mt dng khng penicillin ca N. gonorrhoeae v cng c th s dng cung cp thng tin v dch t hc. Cc chng c c ch khng qua trung gian chromosome ch c th pht hin bng phng php khoanh giy khuch tn v MIC pha long trn thch. (8) Gonococci vi khoanh giy khng sinh penicillin 10-n v v ng knh vng c ch 19 mm thng l chng sinh lactamase. Tuy nhin, th nghim lactamase vn c a dng hn cc phng php th nghim tnh nhy cm khc v chnh xc v nhanh pht hin cc chng khng penicillin qua trung gian plasmid. CEPHEMS (NG TIM) (Bao gm cephalosporins I, II, III, v IV. Tham kho Ch thch I) C Cefotaxime 30 g 31 0.5

Xem lu (5)

M100-S21 hoc 30 g 35 0.25 ceftriaxone C Cefoxitin 30 g 28 24-27 23 2 4 8 C Cefuroxime 30 g 31 26-30 25 1 2 4 O Cefepime 30 g 31 0.5 O Cefmetazole 30 g 33 2832 27 2 4 8 O Cefotetan 30 g 26 2025 19 2 4 8 O Ceftazidime 30 g 31 0.5 O Ceftizoxime 30 g 38 0.5 CEPHEMS (NG UNG) C Cefixime hoc 5 g 31 0.25 C Cefpodoxime 10 g 29 0.5 Inv. Cefetamet 10 g 29 0.5 TETRACYCLINES (9) Cc chng nhy cm vi tetracycline cng c xem nh nhy cm vi doxycycline v minocycline C Tetracycline 30 g 38 31-37 30 0.25 0.5-1 2 C

Xem lu (2) Xem lu (3) Xem lu (5) Xem lu (2) Xem lu (2) Xem lu (5) Xem lu (5) Xem lu (5) Xem lu (5)

(10) Gonococci vi khoanh giy tetracycline 30-g ng knh vng c ch 19 mm thng chng t l chng N. Gonorrhoeae khng tetracycline qua trung gian plasmid (TRNG). Nhng chng ny nn khng nh li bng phng php pha long (MIC 16 g/mL).

FLUOROQUINOLONES C Ciprofloxacin C hoc ofloxacin O Enoxacin O Gatifloxacin O Grepafloxacin O Lomefloxacin O Trovafloxacin Inv. Fleroxacin AMINOCYCLITOLS

5 g 5 g 10 g 5 g 5 g 10 g 10 g 5 g

41 31 36 38 37 38 34 35

28-40 25-30 32-35 34-37 28-36 27-37 29-34

27 24 31 33 27 26 28

0.06 0.25 0.5 0.125 0.06 0.12 0.25 0.25

0.12 0.5 0.51 1 0.25 0.12 0.5 0.251 0.5

1 2 2 0.5 1 2 1

Xem lu (5)

M100-S21 C Spectinomycin 100 g 18 15-17 14 32 64 128 Xem lu (2) Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; MIC, Nng c ch ti thiu, NAD, nicotinamide adenine dinucleotide; QC, m bo cht lng xt nghim; PABA, para-aminobenzoic axit; QC, kim sot cht lng; TRNG, tetracycline-resistant Neisseria gonorrhoeae, Bng 2G. Tiu chun din gii qu ng knh vng c ch v nng c ch ti thiu (MIC) i vi Streptococcus pneumoniae iu kin th nghim Mi trng: Khoanh giy khuch tan: MHA vi 5% mu cu Pha long canh thang: CAMHB vi LHB (2.5 n 5% v/v) (Xem M07-A8 hng dn chun b LHB) Pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352 oC Khng sinh : 5% CO2, 20-24h Pha long: hiu kh, 20-24h Cc xut kim sot cht lng ti thiu (Xem bng 3B v 4B i vi gii hn QC cho php) Streptococcus pneumoniae ATCC 49619

Huyn dch vi khun: iu kin nui cy:

Lu chung (1) i vi khng sinh , o ng knh vng c ch (v d, xc nh ranh gii vng c ch bng mt thng), bao gm ng knh khoanh giy. Soi a mi trng trn nn en vi nh sng phn chiu tr trng hp linezolid, oxacilin v vancomycin nn s dng nh sng xuyn qua. Xc nh ranh gii vng c ch bng mt thng, khng c s pht trin r rng ca vi khun. B qua s pht trin yu v cc khun lc nh li ti ch c th pht hin khi soi di knh lp hoc knh hin vi b ca vng c ch. i vi trimethoprim v sulfonamides, cc cht i khng trong mi trng c th cho php vi khun pht trin nh; do c th b qua s pht trin yu ny (khng qu 20%) v o ng knh vng c ch vi ranh gii xc nh bng mt thng. Amoxicillin, ampicillin, cefepime, cefotaxime, ceftriaxone, cefuroxime, ertapenem, imipenem, v meropenem c th c dng iu tr vim phi; tuy nhin, trn thc t khng tin hnh th nghim tnh nhy cm bng phng php khoanh giy khuch tn vi cc loi khng sinh ny do phng php khoanh giy khuch tn khng ng tin cy. Tc dng in vitro c pht hin tt nht bng phng php MIC.

(2)

(3)

M100-S21 Penicillin v cefotaxime hoc ceftriaxone hoc meropenem cn c th bng phng php MIC ng tin cy (v d nh c m t trong ti liu CLSI-M7-A8) v bo co thng qui vi cc chng S. pneumonia phn lp t dch no ty . Cc chng ny cn tin hnh th nghim vi vancomycin bng phng php MIC hoc khoanh giy khuch tn. i vi mt s cp vi khun/khng sinh, hin tng khng hoc him khi pht hin chng khng khng cho php xc nh bt k mt kt qu no ngoi nhy cm. i vi cc chng cho kt qu khng nhy cm, ton b qu trinh phn lp nh danh v tin hnh th nghim nhy cm khng sinh cn c lm li (Xem Ph lc A).

(4)

LU :

Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc

M100-S21

Bng 2G. (Tip) Nhm th Khng sinh nghim/ bo co PENICILLINS

Hm lng

ng knh vng c ch (mm) S I R

im gy MIC tng ng (g/mL) S I R

Lu

(5) i vi chng khng vim mng no (khng phn lp t dch no ty hoc bnh nhn khng c biu hin vim mng no), gi tr MIC penicillin c th d on tnh nhy cm vi cc khng sinh nhm -lactams khc nh sau: Penicillin MIC 0.06 g/mL (hoc ng knh vng c ch ca oxacillin ng knh 20 mm) cho thy chng nhy cm vi ampicillin (ung v tim), amoxicillin, amoxicillin-clavulanic axit, ampicillin-sulbactam, cefaclor, cefdinir, cefditoren, cefepime, cefotaxime, cefprozil, ceftizoxime, ceftriaxone, cefuroxime, cefpodoxime, ertapenem, imipenem, loracarbef, v meropenem. Penicillin MIC 2 g/mL chng t chng nhy cm vi: amoxicillin, amoxicillin-clavulanic axit, cefepime, cefotaxime, ceftriaxone, v ertapenem. Xem lu (3) A Penicillin 1 g oxacillin 20 (6) Cc chng ph cu vi khoanh giy oxacillin ng knh 20 mm hoc vi penicillin MIC 0.06 g/mL c th xem nh nhy cm vi penicillin.Cc chng vi ng knh oxacillin 19 mm nn c xc nh MIC ca penicillin v cefotaxime hoc ceftriaxone hoc meropenem bi v ng knh 19 mm thng xy ra vi cc chng khng, khng trung gian hoc nhy cm vi penicillin. Cc chng ny khng nn bo co kt qu l khng vi penicillin khi cha tin hnh xt nghim MIC penicillin. (7) Rx: Liu penicillin tim tnh mch t nht 2 triu n v mi 4h ngi ln c

Penicillin tim (khng vim

mng no)

M100-S21 chc nng thn bnh thng (12 triu n v mi ngy) c th c dng iu tr bnh nhm vim phi khng vim mng no do cc chng c MIC penicillin 2 g/mL. Cc chng khng trung gian vi kt qu MIC 4 g/mL c th cn liu 18 n 24 triu n v mi ngy. (8) i vi cc chng khng phi phn lp t dch no ty, bo co c i vi c 2 trng hp th hin vim mng no v khng th hin vim mng no. (9) Rx: S dng penicillin iu tr vim mng no cn liu ti a penicillin tim tnh mch (v d, t nht 3 triu n v mi 4h ngi ln c chc nng thn bnh thng). (10) i vi cc chng phn lp t dch no ty, ch bo co cc trng hp th hinvim mng no.

Penicillin tim (vim mng no)

0.06

0.12

Penicillin 0.06 0.12-1 2 (penicillin V ung) C Amoxicillin 2 4 8 (khng vim 2/1 4/2 8/4 C mng no) Amoxicillinclavulanic axit (khng vim mng no) CEPHEMS (NG UNG) (Bao gm cephalosporins th h I, II, III, IV. Tham kho Ph lc I)

Cefepime (vim mng no)

0.5

Cefepime (khng vim mng no)

M100-S21 (11) i vi cc chng phn lp t Dch no ty, ch bo co cho cc trng hp th hin vim mng no. Khng c ch nh ca FDA v vic s dng cefepime trong iu tr vim mng no. (12) Hoa K, ch cc trng hp th hin khng vim mng no v bao gm ghi ch khng vim mng no trong bo co. (13) i vi cc chng phn lp t Dch no ty, ch bo co vi cc trng hp th hin vim mng no. (14) Rx: S dng cefotaxime hoc ceftriaxone liu ti a trong iu tr vim mng no. Xem lu (3). (15) i vi cc chng khng phn lp t Dch no ty, bo co th hin cho c vim mng no v khng vim mng no.

B B

Cefotaxime (vim mng no) Ceftriaxone (vim mng no)

0.5 0.5

1 1

2 2

Cefotaxime (khng vim mng no) Ceftriaxone (khng vim mng no) C Cefuroxime (ng tim) CEPHEMS (UNG) C Cefuroxime (ung) O Cefaclor O Cefdinir O Cefpodoxime O Cefprozil O Loracarbef CARBAPENEMS

B B

1 1

2 2

4 4

0.5

1 1 0.5 0.5 2 2

2 2 1 1 4 4

4 4 2 2 8 8

M100-S21 B C C Meropenem Ertapenem Imipenem 0.25 1 0.12 0.5 2 0.25 0.5 1 4 1 Xem lu (3)

GLYCOPEPTIDES B Vancomycin

30 g

17

Xem lu (3) v (4)

MACROLIDES (16) Tnh nhy cm v khng vi azithromycin, clarithromycin v dirithromycin c th c d on bng s dng erythromycin. (17) Khng bo co thng qui vi cc chng phn lp t tit niu. A Erythromycin 15 g 21 16-20 15 0.25 0.5 1 O Azithromycin 15 g 18 14-17 13 0.5 1 2 O Clarithromycin 15 g 21 17-20 16 0.25 0.5 1 O Dirithromycin 15 g 18 14-17 13 0.5 1 2 KETOLIDES B Telithromycin 15 g 19 16-18 15 1 2 4 TETRACYCLINES B Tetracycline

30 g

23

19-22

18

(18) Cc chng nhy cm vi tetracycline th c th xem nh nhy cm vi doxycycline v minocycline

FLUOROQUINOLONES B Gemifloxacin 5 g B Levofloxacin 5 g B Moxifloxacin 5 g B Ofloxacin 5 g O Gatifloxacin 5 g O Grepafloxacin 5 g O Sparfloxacin 5 g O Trovafloxacin 10 g THUC C CH CON NG FOLATE A Trimethoprim1.25/23.75 sulfamethoxazole g PHENICOLS C Chloramphenicol 30 g

23 17 18 16 21 19 19 19 19

20-22 14-16 15-17 13-15 18-20 16-18 16-18 16-18 16-18

19 13 14 12 17 15 15 15 15

0.12 2 1 2 1 0.5 0.5 1 0.5/9.5

0.25 4 2 4 2 1 1 2 1/19 2/38 -

0.5 8 4 8 4 2 2 4 4/76

21

20

Xem lu (17)

M100-S21 ANASAMYCINS C Rifampin 5 g 19 17-18 16 1 2 4 (19) Rx: Rifampin khng nn s dng n c trong iu tr

LINCOSAMIDES B Clindamycin 2 g 19 16-18 15 0.25 0.5 1 Xem lu (17) STREPTOGRAMINS O Quinupristin15 g 19 16-18 15 1 2 4 dalfopristin OXAZOLIDINONES C Linezolid 30 g 21 2 Xem lu (4) Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; FDA, LHB, Mu nga ly gii; MHB, Canh thang Mueller-Hinton; MIC, Nng c ch ti thiu (Nng khng sinh ti thiu c ch vi khun);Cc qun l an ton thuc v thc phm; QC, m bo cht lng xt nghim;

M100-S21 Bng 2H-1. Tiu chun din gii ng knh vng c ch v MIC i vi Streptococcus spp. tan huyt beta iu kin th nghim Mi trng: Khng sinh : MHA b sung 5% mu cu Pha long canh thang: CAMHB vi LBH (2.5 n 5% v/v); CAHMB cn c b sung 50 g/mL calcium i vi daptomycin (xem M07-A8 hng dn chun b LHB) Pha long trn thch MHA vi thch mu cu (5% v/v) (khi xt nghim khng sinh sulfonamide, nn dng LHB); pha long trn thch cha nh gi vi daptomycin Pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352 oC, Khng sinh : 5% CO2, 20-24h Cc phng php pha long: hiu kh; 20-24h (CO2, nu cn thit cho vi khun pht trin khi pha long trn thch) Lu chung (1) i vi phng php khoanh giy khuch tn, o ng knh vng c ch (bng mt thng), bao gm ng knh khoanh giy khng sinh. Ranh gii vng c ch c xc nh l vng trong bng mt thng khng quan st thy s pht trin ca vi khun. M np a thch, o ng knh vng c ch t pha trn b mt thch bng nh sng phn chiu. B qua s pht trin yu ca cc khun lc nh li ti mp ng knh vng c ch m ch c th quan st bng knh lp hoc knh hin vi. (2) i vi bng ny, nhm tan huyt beta bao gm cc chng Streptococci khun lc ln nhm A, sinh m (S. pyogenes), nhm C, hoc G v cc chng nhm B (S. agalactiae). Cc chng khun lc nh tan huyt beta nhm A, C, F, hoc G (S. anginosus, nh danh trc l S. milleri) c xem l mt phn ca nhm viridans, do p dng tiu chun c kt qu cho nhm viridans vi cc chng ny (xem Bng 2H-2). (3) Penicillin v Ampicillin l cc khng sinh c la chn cho iu tr nhim trung gy ra bi cc cu khun tan huyt beta (-hemolytic streptococcal infection). Th nghim tnh nhy cm khng sinh (khng sinh ) ca penicillin v cc khng sinh -lactam khc (c FDA ph chun) vi cc cu khun tan mu beta khng cn thit phi thc hin thng quy. Bi v, cc chng khng nhy cm (MIC ca penicill > 0,12 v ampicillin > 0,25 g/ml) l rt him trong bt c cu khun tan mu beta no v cha c bo co no cho Streptococcus pyogenes.Trong trng hp thc hin khng sinh pht hin bt c mt chng cu khun tan mu beta l khng nhy cm, ton b qu trnh nh danh, khng sinh phi c thc hin li. Nu qu trnh xc nhn l ng, bo co ti cc trung tm dch t (tham kho Ph lc A c thm hng dn) Cc xut kim sot cht lng ti thiu (Xem bng 3Bv 4B v gii hn QC cho php) Streptococcus pneumoniae ATCC 49619

Huyn dch vi khun: iu kin nui cy:

M100-S21 (4) Tiu chun din gii kt qu cho cu khun tan mu beta (Streptococcus spp. -hemolytic group) c xut da trn biu phn b khng sinh ca rt nhiu loi khc nhau, dc ng hc ca khng sinh, cc ti liu cng b trc v kinh nghim lm sng ca tng thnh vin trong tiu y ban. Hin ti, cha c mt thu thp h thng cc s liu lm sng cho nhiu khng sinh trong nhm. (5) i vi mt s cp vi khun/khng sinh, hin tng khng hoc him khi pht hin chng khng khng cho php xc nh bt k mt kt qu no ngoi nhy cm. i vi cc chng cho kt qu khng nhy cm, ton b qu trinh phn lp nh danh v tin hnh th nghim nhy cm khng sinh cn c lm li (Xem Ph lc A).

LU :

Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc

M100-S21 Bng 2H-1 (Tip) Nhm th nghim/bo co Khng sinh Hm lng Gii hn ng knh vng c ch (mm) S I R Gii hn nng c ch ti thiu (g/mL) S I R Lu

PENICILLINS (6) i vi cc nhm vi khun sau y, nu vi khun nhy cm vi penicillin th c th xem nh nhy cm vi cc khng sinh c lit k sau y m khng th nghim li. i vi Streptococci tan huyt beta (Nhm A, B, C, G): ampicillin, amoxicillin, amoxicillin-clavulanic axit, ampicillin-sulbactam, cefazolin, cefepime, cephradine, cephalothin, cefotaxime, ceftriaxone, ceftizoxime, imipenem, ertapenem, v meropenem. Ring i vi Streptococci nhm A: cefaclor, cefdinir, cefprozil, ceftibuten, cefuroxime, cefpodoxime, and cephapirin. Xem lu (5) (7) Cc chng Streptococci tan mu c MIC penicillin ln hn 0.12 g/mL hoc MIC ampicillin ln hn 0.25 g/mL cha c theo di; gi cc chng ny n phng xt nghim cao hn. CEPHEMS (NG TIM) (Bao gm cephalosporins I, II, III, v IV. Tham kho Bng ch gii I) Xem lu (5) v (6) B Cefepime hoc 30 g 24 0.5 B cefotaxime hoc 30 g 24 0.5 B ceftriaxone 30 g 24 0.5 Xem lu (5) v (6) CARBAPENEMS O Ertapenem 1 O Meropenem 0.5 GLYCOPEPTIDES B Vancomycin 30 g 17 1 Xem lu (5). LIPOPEPTIDES C Daptomycin 1 (7) Daptomycin khng c php bo co vi nhng chng phn lp c t ng h hp di. Xem lu (5). MACROLIDES (8) Mc nhy cm v khng vi azithromycin, clarithromycin, v dirithromycin c th c suy lun t kt qu xt nghim vi erythromycin. A A Penicillin hoc ampicillin 10 n v 10 g 24 24 0.12 0.25 -

M100-S21 (9) Khng bo co thng qui vi cc chng phn lp t ng tit niu. A Erythromycin 15 g 21 16-20 15 0.25 0.5 1 (10) Rx: Khng sinh d phng cho Streptococci nhm B l penicillin hoc ampicillin. i vi ph n d ng penicillin nguy c qu mn thp th c th dng cefazolin, nu nguy c qu mn cao th c th dng clindamycin hoc erythromycin. Streptococci nhm B nhy cm vi ampicillin, penicillin, v cefazolin, c th khng vi clindamycin v/hoc erythromycin. Khi mt chng streptococcus nhm B phn lp t ph n mang thai, d ng vi penicillin (nguy c qu mn cao) th nn xt nghim vi clindamycin v erythromycin v bo co kt qu.

O Azithromycin O Clarithromycin O Dirithromycin TETRACYCLINES O Tetracycline

15g 15g 15g 30 g

18 21 18 23

14-17 17-20 14-17 19-22

13 16 13 18

0.5 0.25 0.5 2

1 0.5 1 4

2 1 2 8 (11) Cc chng nhy cm vi tetracycline th cng nhy cm vi doxycycline v minocycline.

FLUOROQUINOLONES C Levofloxacin C Ofloxacin O Gatifloxacin O Grepafloxacin O Trovafloxacin PHENICOLS C Chloramphenicol LINCOSAMIDES A Clindamycin

5 g 5 g 5 g 5 g 10 g 30 g

17 16 21 19 19 21

14-16 13-15 18-20 16-18 16-18 18-20

13 12 17 15 15 17

2 2 1 0.5 1 4

4 4 2 1 2 8

8 8 4 2 4 16 Xem lu (9)

2 g

19

16-18

15

0.25

0.5

Xem lu (9) v (10). (12) Khng clindamycin kch thch c th

M100-S21 c pht hin bng phng php khoanh giy khuch tn vi s xut hin ca vng D. v phng php vi pha lonh Xem Bng 2H1-S7 v Phn 12 ti liu M02-A10 v Phn 13 ti liu M07-A8. STREPTOGRAMINS C Quinupristin15 g 19 16-18 15 1 2 4 (13) Bo co i vi S. pyogenes. dalfopristin OXAZOLIDINONES C Linezolid 30 g 21 2 Xem lu (5) Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; FDA, LHB, Mu nga ly gii; MHB, Canh thang Mueller-Hinton; MIC, Nng c ch ti thiu (Nng khng sinh ti thiu c ch vi khun);Cc qun l an ton thuc v thc phm; QC, m bo cht lng xt nghim;

M100-S21 Bng b sung 2H-1-S7. Th nghim sng lc khng clindamycin kch thch cho Streptococus spp tan mu beta trong bng 2H-1 Th nghim sng lc Khng clinidamycin khch thch Nhm vi khun Cc Streptococcus spp tan mu beta khng erythromycin v nhy cm hoc khng trung gian vi clindamycina Phng php xt nghim Mi trng Nng khng sinh Huyn dch vi khun iu kin nui cy Thi gian nui cy Kt qu Khoanh giy khuch tn Vi pha long canh thang MHA b sung thm mu cu (5%) hoc TSA b CAMHB vi LHB (2,5-5%) sung thm mu cu (5%) Hai khoanh giy khng sinh erythromycin 15 g 1 g/mL erythromycin v 0,5 g/mL clindamycin trong cng v clindamycin 2 g, t cch nhau 12 mm mt ging Phng php khoanh giy khuch tn chun c Phng php vi pha long canh thanh chun c khuyn khuyn co co 352 C; 5% CO2 352 C; hiu kh. 20-24 gii 20-24 gii Nu xut hin vng c ch c hnh dng khng Bt k s pht trin no=khng clindamycin do kch thch trn bn cnh khoanh erythromycin (vng ch D)=khng clindamycin do kch thch Khng pht trin=khng khng clindamycin do kch thch Khun lc pht trin nh trong vng c ch xung quanh khoanh giy clindamycin=khng clindamycin ( sn c) k c khi khng xut hin vng D Bo co cc chng khng clindamycin do kch thch vi dng lu khng clindamycin

Xt nghim thm v Bo co

Ghi ch Chng ny c cho l khng clindamycin da trn s pht hin khng clindamycin do kch thch. Clindamycin c th vn c hiu qu trn lm sng mt s bnh nhn xut kim sot cht Streptococcus pneumoniae ATCC 49619 Streptococcus pneumoniae ATCC 49619 lng S. aureus ATCC BAA-976 hoc S. aureus ATCC 29213 khng pht trin S. aureus ATCC BAA-977 pht trin Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; MHA, Thch Mueller-Hinton; MIC, Nng c ch ti thiu, QC, m bo cht lng xt nghim; LHB, Mu nga ly gii; TSA, Tryptic soy agar (thch trit xut u tng) a S khc bit lm sng c to ra gia chng Streptococcus spp khng clindamycin khch thch vi cc chng khc trong nhm hin cha r rng. Thc hin th nghim sng lc khng clindamycin khch thch khng cn thit vi mi chng khng erythromycin v nhy vi clindamycin. Tuy nhin, tt c cc chng phn lp c t cc nhim trng bi nhim cn phi c thc hin th nghim. Khi phn lp c Streptococcus nhm B t ph n c thai d ng vi penicillin nng (nguy c cao vi qu mn) clindamycin v erythromycin phi c lm khng sinh v bo co (xem lu [10] trong bng 2H-1)

M100-S21 Bng 2H-2. Tiu chun c ng knh vng c ch v MIC i vi Streptococcus spp. Nhm Viridans iu kin th nghim Mi trng: Khoanh giy khuch tn: MHA b sung 5% mu cu Pha long canh thang: CAMHB vi LBH (2.5 n 5%); CAHMB cn c b sung 50 g/mL calcium i vi daptomycin (xem M07-A8 hng dn chun b LHB) Pha long trn thch MHA vi thch mu cu (5%) (khi xt nghim khng sinh sulfonamide, nn dng LHB); pha long trn thch cha nh gi vi daptomycin Pha huyn dch vi khun trc tip t khun lc vi mt vi khun tng ng c chun 0.5 McFarland 352 oC, Khng sinh : 5% CO2, 20-24h Cc phng php pha long: hiu kh; 20-24h (CO2, nu cn thit cho vi khun pht trin khi pha long trn thch) Cc xut kim sot cht lng ti thiu (Xem bng 3B v 4B v gii hn QC cho php) Streptococcus pneumoniae ATCC 49619

Huyn dch vi khun: iu kin nui cy:

Lu chung (1) i vi phng php khoanh giy khuch tn, o ng knh vng c ch (bng mt thng), bao gm ng knh khoanh giy khng sinh. Ranh gii vng c ch c xc nh l vng trong bng mt thng khng quan st thy s pht trin ca vi khun. M np a thch, o ng knh vng c ch t pha trn b mt thch bng nh sng phn chiu. B qua s pht trin yu ca cc khun lc nh li ti mp ng knh vng c ch m ch c th quan st bng knh lp hoc knh hin vi. (2) Cc chng Streptococci nhm viridans bao gm 5 nhm ph (gm rt nhiu loi trong mi nhm): nhm mutans, nhm salivariusnhm bovis, nhm anginosus (trc y gi l nhm S. milleri) v nhm. mitis. nhm anginosus bao gm cc chng tan huyt beta khun lc nh vi nhm khng nguyn A, C, F, hoc G. Thng tin chi tit v tng loi, tham kho cc ti liu vi sinh lm sng gn y. (3) Tiu chun c kt qu cho cc Streptococci spp nhm viridansc xut da trn biu phn b khng sinh ca rt nhiu loi khc nhau, dc ng hc ca khng sinh, cc ti liu cng b trc v kinh nghim c lm sng ca tng thnh vin trong tiu y ban. Hin ti, cha c mt thu thp h thng cc s liu lm sng cho nhiu khng sinh trong nhm.

M100-S21 (4) i vi mt s cp vi khun/khng sinh, hin tng khng hoc him khi pht hin chng khng khng cho php xc nh bt k mt kt qu no ngoi nhy cm. i vi cc chng cho kt qu khng nhy cm, ton b qu trinh phn lp nh danh v tin hnh th nghim nhy cm khng sinh cn c lm li (Xem Ph lc A). LU : Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc

M100-S21 Bng 2H-2 (Tip) Nhm Khng sinh Hm lng Gii hn ng knh vng c ch (mm) S I R Gii hn nng c ch ti thiu (g/mL) S I R 0,12 0,25 0,25-2 0,5-4 4 8 Bn lun

PENICILLINS A Penicillin A Ampicillin

(5) Khoanh giy khuch tn khng cho kt qu ng tin cy i vi penicillin v ampicillin. (6) Streptococci nhm viridans phn lp t cc vng v khun (v d, dch no ty, mu, xng) cn xt nghim tnh nhy cm vi penicillin bng phng php MIC. (7) Rx: Cc chng khng trung gian vi penicillin v ampicillin c th s phi phi hp vi mt khng sinh nhm aminoglycoside trong iu tr.

CEPHEMS (NG TIM) (Bao gm cephalosporins I, II, III, v IV. Tham kho Bng ch gii I) B Cefepime 30 g 24 22-23 21 1 2 4 B Cefotaxime 30 g 28 26-27 25 1 2 4 B Ceftriaxone 30 g 27 25-26 24 1 2 4 CARBAPENEMS O Ertapenem 1 O Meropenem 0.5 GLYCOPEPTIDES B Vancomycin 30 g 17 1 LIPOPEPTIDES O Daptomycin 1 -

Xem lu (4) Xem lu (4) Xem lu (4). (8) Phng php khoanh giy khuch tn khng cho kt qu ng tin cy i vi daptomycin. (9) Daptomycin khng c php bo co vi nhng chng phn lp t ng h hp di. Xem lu (4).

M100-S21 MACROLIDES (10) Mc nhy cm v khng vi azithromycin, clarithromycin, v dirithromycin c th c suy lun t kt qu xt nghim vi erythromycin. (11) Khng bo co thng qui vi cc chng phn lp t ng tit niu. C Erythromycin 15 g 21 16-20 15 0.25 0.5 1 O Azithromycin 15g 18 14-17 13 0.5 1 2 O Clarithromycin 15g 21 17-20 16 0.25 0.5 1 O Dirithromycin 15g 18 14-17 13 0.5 1 2 TETRACYCLINES O Tetracycline 30 g 23 19-22 18 2 4 8 (12) Cc chng nhy cm vi tetracycline th cng nhy cm vi doxycycline v minocycline. FLUOROQUINOLONES C Levofloxacin 5 g 17 14-16 13 2 4 8 C Ofloxacin 5 g 16 13-15 12 2 4 8 O Gatifloxacin 5 g 21 18-20 17 1 2 4 O Grepafloxacin 5 g 19 16-18 15 0.5 1 2 O Trovafloxacin 10 g 19 16-18 15 1 2 4 PHENICOLS C Chloramphenicol 30 g 21 18-20 17 4 8 16 Xem lu (11) LINCOSAMIDES C Clindamycin 2 g 19 16-18 15 0.25 0.5 1 Xem lu (11) STREPTOGRAMINS O Quinupristin15 g 19 16-18 15 1 2 4 dalfopristin OXAZOLIDINONES C Linezolid 30 g 21 2 Xem lu (4) Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; CAMHB, canh thang Mueller-Hinton iu chnh cation; FDA, LHB, Mu nga ly gii; MHB, Canh thang Mueller-Hinton; MIC, Nng c ch ti thiu (Nng khng sinh ti thiu c ch vi khun);Cc qun l an ton thuc v thc phm; QC, m bo cht lng xt nghim;

M100-S21 Bng 2I. Tiu chun c ng knh vng c ch v MIC i vi Neisseria meningitidis iu kin th nghim Mi trng: Khoanh giy khuch tn: MHA vi 5% mu cu Pha long canh thang: CAMHB b sung 2.5 n 5% LHB (xem M07-A8 hng dn chun b LHB) Pha long trn thch: MHA b sung 5% mu cu Huyn dch vi khun: Pha huyn dch vi khun trc tip t khun lc sau tng sinh 20-24h trn thch s c la nui cy 35 oC; 5% CO2 vi mt vi khun tng ng c chun 0.5 McFarland. Tuy nhin, huyn dch vi khun c 0.5 McFarland t thch mu cu s cha t hn khong 50% CFU/ml. Huyn dch ny phi m khi pha dung dch pha long cui trc khi cy vo cc tup, nh phng php m khun lc 352 oC, 5% CO2, 20-24h Cc xut kim sot cht lng ti thiu (Xem bng 3A, 3B, 4A v 4B v gii hn QC cho php) Streptococcus pneumoniae ATCC 49619 Khoanh giy khuch tn: trong 5% CO2 i vi v hoc i v Phng php vi pha long canh thang: hiu kh hoc 5% CO2 (tr QC i vi azithromycin bt buc phi nui cy trong iu kin hiu kh). E. coli ATCC 25922 Khoanh giy khuch tn, vi pha long canh thang, pha long trn thch( trong iu kin hiu kh hoc 5% CO2) i vi ciprofloxacin, nalidixic axit, minocycline v sulfisoxazole.

iu kin nui cy:

Lu chung Quan trng: Cc thng tin y v cnh bo an ton, tham kho ti liu An ton sinh hc trong Phng xt nghim Vi sinh v Y sinh. Ti bn ln th 5. Washington, DC: Vn phng In n Chnh ph lin bang Hoa K; 2007. http://www.cdc.gov/OD/ohs/biosfty/bmbl5/bmbl5toc.htm. (1) Cnh bo: Thao tc tt c cc xt nghim khng sinh i vi N. meningitidis trong t an ton sinh hc (BSC). Thao tc pha huyn dch vi khun N. meningitidis bn ngoi t an ton sinh hoc c nguy c phi nhim v mc bnh vim mng no do no m cu cao. T l mc bnh vim mng no cu mc phi phng xt nghim do ri ro ngh nghip ti 50%. Phi nhim vi cc ht nh hoc kh dung N. meningitidis l cc nguy c ch yu gy nhim khun mc phi phng xt nghim. Cn tun th cht ch cc qui trnh bo v trnh cc ht nh v kh dung N. meningitidis trong qu trnh thao tc vi sinh (bao gm c xt nghim khng sinh ) i vi cc chng N. meningitides. Cc cnh bo c xut: Cc bnh phm cn nui cy v nh danh N. meningitidis, khng lin quan n bnh nhim trng xm ln, c th thao tc trong nhng trang thit b an ton sinh hc cp 2 (BSL-2), tun th cht ch thc hnh chun BSL-2, cc thao tc v cc thit b an ton. Tt c cc chng N. meningitidis phn lp t cc v tr v khun nn thao tc trong BSC. Nu khng c BSC, hn ch cc bc phi thao tc bng tay vi cc chng ny, hn ch nhum Gram hoc xc nh nhm huyt thanh bng dung dch nc mui phenol ha, mc o bo h v eo gng tay. Tun

(2)

M100-S21 th theo thc hnh theo an ton sinh hc cp 3 (BSL-3), cc thao tc v thit b cp tng ng i vi cc bnh phm c nguy c sinh kh dung v cc ht nh cao hoc cc bc c th to ra chng vi nng hoc lng ln. Nu BSL-2 hoc BSL-3 khng sn c ti phng xt nghim, gi mu n phng xt nghim cao hn c cc thit b t nht mc BSL-2. (3) Cc cn b phng xt nghim c nguy c phi nhim thng xuyn vi cc ht kh dung N. meningitidis cn c xem xt tim phng theo khuyn co ca Trung tm Kim sot v Phng bnh (CDC) Hi ng t vn tim chng (www.cdc.gov). Vic tim chng c th gip gim nguy c, tuy nhin khng loi b ht c nguy c nhim khun, bi v hiu qu di 100% v khng c hiu qu bo v i vi cc chng nhm huyt thanh B, l nguyn nhn thng gp gy nhim khun mc phi phng xt nghim. i vi phng php khoanh giy khuch tn, o ng knh vng c ch (v d, xc nh ranh gii vng c ch bng mt thng), bao gm ng knh khoanh giy. Soi a mi trng trn nn en vi nh sng phn chiu tr trng hp linezolid, oxacilin v vancomycin nn s dng nh sng xuyn qua. Xc nh ranh gii vng c ch bng mt thng, khng c s pht trin r rng ca vi khun. B qua s pht trin yu v cc khun lc nh li ti ch c th pht hin khi soi di knh lp hoc knh hin vi b ca vng c ch. i vi trimethoprim v sulfonamides, cc cht i khng trong mi trng c th cho php vi khun pht trin nh; do c th b qua s pht trin yu ny (khng qu 20%) v o ng knh vng c ch vi ranh gii xc nh bng mt thng. Cc tiu chun c kt qu c da trn biu phn b khng sinh vi nhiu khng sinh, dc ng ca khng sinh, cc ti liu cng b, v kinh nghim ca tng thnh vin trong tiu y ban Cha c mt thu thp h thng cc s liu lm sng ca nhiu khng sinh trong bng ny. i vi mt s cp vi khun/khng sinh, hin tng khng hoc him khi pht hin chng khng khng cho php xc nh bt k mt kt qu no ngoi nhy cm.. i vi cc chng cho kt qu khng nhy cm, kt qu nh danh vi khun v xc nh mc nhy cm khng sinh cn c xc nh li. (Xem Ph lc A). i vi azithromycin, tiu chun c kt qu bc u c xy dng s dng kt qu MIC c xc nhbng nui cy trong iu kin hiu kh i vi cc tnh ton dc ng hc.

(4)

(5)

(6)

(7)

LU :

Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc Hm lng ng knh vng c ch (mm) S I R im gy MIC tng ng (g/mL) S I R 0.06 0.12 0.12 0.25 0.5 2 Lu

Nhm th Khng sinh nghim/ bo co PENICILLINS C Penicillin C Ampicillin

(8) Khoanh giy khuch tn vi ampicillin v penicillin cho kt qu khng ng tin cy

0.251 CEPHEMS C Cefotaxime hoc C Ceftriaxone CARBAPENEMS C Meropenem MACROLIDES C Azithromycin

M100-S21 i vi Neisseria meningitidis. Nn dng phng php MIC i vi cc chng ny Xem lu (6) Xem lu (6) Xem lu (6) Xem lu (6) v (7). (9) C th ch thch hp dng trong d phng cc trng hp tip xc vi meningococcal. Tiu chun din gii ny khng p dng i vi bnh nhn vim mng no m xm ln.

30 g 30 g 10 g 15 g

34 34 30 20

0.12 0.12 0.25 2

TETRACYCLINES C Minocycline 30 g 26 2 Xem lu (6) v (9) FLUOROQUINOLONES (10) i vi mc ch gim st, MIC ca axit nalidixic 8 g/mL hoc ng knh vng c ch 25 mm ng ngha vi gim nhy cm vi fluoroquinolone. C Ciprofloxacin 5 g 35 33-34 32 0.03 0.06 0.12 Xem lu (9) C Levofloxacin 0.03 0.06 0.12 THUC C CH CON NG FOLATE C Sulfisoxazole 2 4 8 Xem lu (9) C 1.25/ Trimethoprim 30 26-29 25 0.12/ 0.25/ 0.5/ (11) y l khoanh giy c a dng trong sulfamethoxazole 23.75 g 2.4 4.75 9.5 pht hin s khng sulfonamide. Trimethoprim-sulfamethoxazole dng d on tnh nhy cm v khng vi Trimethoprim-sulfamethoxazole v sulfonamides. Sulfonamides c th ch thch hp dng trong d phng cc trng hp tip xc vi no m cu PHENICOLS C Chloramphenicol 30 g 26 20-25 19 2 4 8 (12) Khng bo co thng qui cc chng phn lp t ng niu ANASAMYCINS

M100-S21 C Rifampin 5 g 25 20-24 19 0.5 1 2 Xem lu (9). Vit tt: ATCC, tn thng mi ca h thng chng chun theo tiu chun ca Hoa K; AST, th nghim nhy cm khng sinh; BSC, t an ton sinh hc; BSL2, An ton sinh hc cp 2; BSL3, An ton sinh hc cp 3; CAMHB, canh thang Mueller-Hinton iu chnh cation; LHB, Mu nga ly gii; MHB, Canh thang Mueller-Hinton; MIC, Nng c ch ti thiu (Nng khng sinh ti thiu c ch vi khun); QC, m bo cht lng xt nghim; CDC, Trung tm kim sot v phng nga dch bnh (Hoa K); CFU, n v khun lc;

M100-S21 Bng 2 J. Tiu chun din gii kt qu cho vi khun k kh iu kin th nghim Mi trng: Pha long canh thang: canh thang Brucella c b sungb sungb sung hemin, Vitamin K1 v mu nga ly gii Pha long trn thch: Thch Brucella c b sungb sungb sung hemin, Vitamin K1 v mu nga ly gii Huyn dch vi khun: Thch: 105 cfu trong mt im Canh thang: 106 cfu/mL iu kin nui cy: 44-48 gii trong 36 oC, k kh Khuyn co QC ti thiu (xem bng 4D v 4E cho khong gi tr QC cho php) Bacteroides fragilis ATCC 25285 Bacteroides thetaiotaomicron ATCC 29714 Clostridium diffcile ATCC 700057 Eubacterium lentum ATCC 43055 Kim tra 2 chng vi pha long trn thch; kim tra mt chng duy nht vi pha long canh thang

Lu chung (1) Khong khng trung gian c xc nh bi s kh khn trong vic c cc im mt v nhm cc gi tr MIC hoc gn nhng nng ranh gii. Ni thng tin kh dng, nhng hng dn din gii c da trn thng tin dc ng hc, khong phn b ca MIC, v nhng nghin cu v hiu qu lm sng. t c nng khng sinh cao nht c th trong cc p se v/hoc cc m ti mu km, iu phi i mt thng xuyn trong nhim trng loi ny, liu lng ti a cho php ca cc khng sinh c khuyn co cho cc php iu tr nhim trng k kh. Khi liu lng ti a c s dng cng vi nhng liu php h tr ph hp, n c tin rng nhng chng vi MIC trong khong nhy cm thng p ng vi phc , v nhng chng vi MIC trong khong khng trung gian c th p ng, nhng s p ng ca bnh nhn cn phi c theo di. Cc liu php h tr nh cc th thut dn lu v ct lc, l cc k quan trng cho iu tr nhim trung k kh hiu qu. LU : Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc Nhm th Khng sinh Lu Tiu chun din gii MIC nghim/bo (g/mL) co S I R Penicillin C Ampicillin 0,5 1 2 (2) Cc thnh vin ca nhm Bacteroides fragilis c cho l khng. Cc vi khun k kh Gram-m khc c th cn c sng lc -lactamase bng test nhanh, nu c th, bo co l khng penicillin, ampicillin, v amoxicillin. Nhng nng khng sinh cao hn trong mu t c: nhim trung gy ra bi cc chng khng sinh -lactamase vi MIC cao hn (2-4 g/mL vi khong ngh dng thuc y ) c th iu tr c. Cc im gii hn ca amoxicillin c cn nhc tng ng vi cc im gii hn ca ampicillin. Nhng thng tin ca cc nghin cu in vitro

M100-S21 cha hon thin ch ra rng hai khng sinh ny c tc dng tng t nhau chng li vi khun k khi khi tin hnh MIC, tuy nhin, cc im gii hn cho amoxicillin cha c thit lp. C C C Mezlocillin Penicillin Piperacillin 32 0,5 32 64 1 64 128 2 128 Xem lu (2) (3) Nhng gi tr MIC s dng c thch mu Brucella hoc thch Wilkins Chalgren (mi trng chun c) c cho l tng ng, da trn nhng t liu in vitro c cng b v mt th nghim hp tc lin trung tm cho nhng khng sinh ny. (4) Nhng gi tr MIC cho thch hoc canh thang vi pha long c cho l tng ng

C Ticarcillin 32 64 128 Phi hp -lactama v c ch -lactamase A Amoxicillin-clavulanic 4/2 8/4 16/8 Xem lu (3) acid A Ampicillin-sulbactam 8/4 16/8 32/16 Xem lu (3) v (4) A Piperacillin-tazobactam 32/4 64/4 128/4 Xem lu (3) A Ticarcillin-clavulanic 32/2 64/2 128/2 Xem lu (3) acid Cephem (ng tim) (bao gm cephalosporin I, II, III, v IV, tham kho ph lc I.) C Cefemetazole 16 32 64 C Cefoperazole 16 32 64 C Cefotaxime 16 32 64 C Cefotetam 16 32 64 Xem lu (3) C Cefoxitin 32 64 128 Xem lu (3) v (4) C Ceftriaxole 16 32 64 Xem lu (3) Carbapenem A Ertapenem 4 8 16 Xem lu (4) A Imipenem 4 8 16 Xem lu (3) A Meropenem 4 8 16 Xem lu (3) Tetracycline C Tetracycline 4 8 16 Fluoroquinolone Moxifloxacin 2 4 8

M100-S21 Lincosamide A Phenicol Clindamycin 2 4 8 Xem lu (3) v (4)

Chloramphenicol 8 16 32 Xem lu (3) v (4) Nitroimidazole A Metronidazole 8 16 32 Xem lu (3) v (4) Vit tt: MIC, Nng c ch ti thiu (Nng khng sinh ti thiu c ch vi khun);

M100-S21 Bng 3A. Khoanh giy khuch tn: Gii hn cho php i vi cc chng kim tra cht lng (chng QC) ca cc chng d nui cy (S dng mi trng Mueller-Hinton khng b sung cc thnh phn khc) Escherichia coli ATCC a 25922 19-26 18-24 16-22 19-24 28-36 Staphylococcus aureus ATCC 25923 20-26 28-36 27-35 29-37 21-26 Pseudomonas aeruginosa ATCC27853 18-26 24-30 23-29 Escherichia coli ATCC 35218bc 17-22 6 13-19 -

Khng sinh Amikacin Amoxicillin-clavulanic axit Ampicillin Ampicillin-sulbactam Azithromycin Azlocillin Aztreonam

Hm lng khoanh giy 30 g 20/10 g 10 g 10/10 g 15 g 75 g 30 g

Carbenicillin Cefaclor Cefamandole Cefazolin Cefdinir Cefditoren Cefepime Cefetamet Cefixime Cefmetazole Cefonicid Cefoperazone Cefotaxime Cefotetan Cefoxitin Cefpodoxime Cefprozil Ceftaroline Ceftazidime Ceftibuten Ceftizoxime Ceftobiprole Ceftriaxone Cefuroxime Cephalothin Chloramphenicol Cinoxacin Ciprofloxacin Clarithromycin Clinafloxacin Clindamycind Colistin

100 g 30 g 30 g 30 g 5 g 5 g 30 g 10 g 5 g 30 g 30 g 75 g 30 g 30 g 30 g 10 g 30 g 30 g 30 g 30 g 30 g 30 g 30 g 30 g 30 g 30 g 100 g 5 g 15 g 5 g 2 g 10 g

23-29 23-27 26-32 21-27 24-28 22-28 31-37 24-29 23-27 26-32 25-29 28-34 29-35 28-34 23-29 23-28 21-27 26-34 25-32 27-35 30-36 30-36 29-35 20-26 15-21 21-27 26-32 30-40 31-40 11-17

27-31 26-34 29-35 25-32 20-28 23-29 25-34 22-28 24-33 25-31 17-23 23-29 19-25 27-33 26-35 16-20 27-35 26-34 22-28 27-35 29-37 19-26 22-30 26-32 28-37 24-30 -

18-24 24-30 23-29 18-22 22-29 12-17 24-30 17-23 25-33 27-35 11-17

M100-S21 -

Daptomycin Dirithromycin Doripenem Doxycycline Enoxacin Ertapenem Erythromycind Faro pe nem Fleroxacin Fosfomycinf Garenoxacin Gatifloxacin Gemifloxacin Gentamicing Grepafloxacin Iclaprim Imipenem Kanamycin Levofloxacin Linezolid Lomefloxacin

30 g 15 g 10 g 30 g 10 g 10 g 15 g 5 g 5 g 200 g 5 g 5 g 5 g 10 g 5 g 5 g 10 g 30 g 5 g 30 g 10 g

27-35 18-24 28-36 29-36 20-26 28-34 22-30 28-35 30-37 29-36 19-26 28-36 14-22 26-32 17-25 29-37 27-33

18-23 18-26 33-42 23-29 22-28 24-31 22-30 27-34 21-27 25-33 30-36 27-33 27-33 19-27 26-31 25-33 19-26 25-30 25-32 23-29

28-35 22-28 13-21 12-20 19-25 20-28 19-25 16-21 20-27 20-28 19-26 22-28

M100-S21 -

M100-S21 Bng 3A (Tip) Escherichia coli ATCC 25922 a 23-29 24-30 28-34 23-29 19-25 28-35 28-35 22-28 22-30 20-25 28-35 29-33 24-30 24-30 13-19 21-26 8-10 30-38 12-20 15-23 Staphylococcus aureus ATCC 25923 23-31 29-37 17-22 25-30 18-24 28-35 16-22 22-31 18-22 17-28 24-28 18-24 26-37 27-36 21-28 -j 26-34 27-33 14-22 24-34 Pseudomonas aeruginosa ATCC27853 27-33 19-25 17-25 17-25 17-23 22-29 17-21 25-33 25-33 14-18 21-29 Escherichia coli ATCC 35218b 12-18 24-30 -

Khng sinh Loracarbef Mecillinam Meropenem Methicillin Mezlocillin Minocycline Moxalactam Moxifloxacin Nafcillin Nalidixic axit Netilmicin Nitrofurantoin Norfloxacin Ofloxacin Oxacillin Penicillin Piperacillin Piperacillin-tazobactam Polymyxin B Quinupristin-dalfopristin Razupenem Rifampin Sparfloxacin Streptomycing Sulfisoxazolei

Hm lng khoanh giy 30 g 10 g 10 g 5 g 75 g 30 g 30 g 5 g 1 g 30 g 30 g 300 g 10 g 5 g 1 g 10 n v 100 g 100/10 g 300 n v 15 g 10 g 5 g 5 g 10 g 250 g hoc 300 g

Teicoplanin Telavancin Telithromycin Tetracycline Ticarcillin Ticarcillin-clavulanic axit Tigecycline Tobramycin Trimethoprimi Trimethoprim-sulfamethoxazolei Trospectomycin Trovafloxacin Ulifloxacin (prulifloxacin)h Vancomycin Vit tt: MHI, Thch Muller-Hinton LU :

30 g 30 g 15 g 30 g 75 g 75/10 g 15 g 10 g 5 g 1.25/23.75 g 30 g 10 g 5 g 30 g

18-25 24-30 24-30 20-27 18-26 21-28 23-29 10-16 29-36 32-38 -

15-21 16-20 24-30 24-30 29-37 20-25 19-29 19-26 24-32 15-20 29-35 20-26 17-21

21-27 20-28 9-13 19-25 21-27 27-33 -

M100-S21 6 21-25 -

Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc Lu

ATCC l tn thng mi ca h thng chng chun theo tiu chun ca M. V cc chng ny d mt plasmid, yu cu cy chuyn v gi chng cn thn; tham kho ti liu M02-A10, Phn 15.4. Chng QC c khuyn co khi tin hnh lm khng sinh vi phc hp -lactama/c ch -lactamase Khi th nghim phng php khoanh giy khuch tn vi khng sinh erythromycin v clindamycin, S. aureus ATCC BAA-977 (khng qua trung gian ermA) v S. aureus ATCCBAA-976 (c ch khng qua bm y macrolide qua trung gian msrA) l cc chng chun c xut s dng vi mc ch nh gi cht lng b sung (v d, o to, nh gi nng lc hoc nh gi th nghim). S. aureus ATCCBAA-977 nn dng khng nh tnh khng clindamycin do kch thch (v d, th nghim vng D dng tnh), trong khi S. aureus ATCC BAA-976 khng nn dng khng nh tnh khng clindamycin do kch thch. S. aureus ATCC 25923 khng nn s dng cho kim sot cht lng thng qui (v d, hng tun, hng ngy) i vi khng sinh erythromycin v clindamycin s dng thch Mueller-Hinton tiu chun. e. Mt s l thch Mueller-Hinton thiu calcium v to vng c ch nh. f. Khoanh giy fosfomycin hm lng 200 g cha 50 g glucose-6-phosphate. g. kim sot gii hn khoanh giy khng sinh gentamicin hm lng 120 g v streptomycin hm lng 300 g, s dng chng Enterococcus faecalis ATCC 29212 (gentamicin:16 n 23 mm; streptomycin: 14 n 20 mm).

a. b. c. d.

M100-S21 h. Ulifloxacin l cht chuyn ha c hot tnh ca khng sinh ang th nghim lm sng prulifloxacin. Ch dng ulifloxacin trong th nghim tnh nhy cm khng sinh. i. Nhng khng sinh ny c th b nh hng nu nng thymidine v thymine vt qu ngng. Xem M2-A9, Phn 7.1.4 hng dn x l cc vn trong kim sot cht lng. j. Razupenem c kim tra bng S. aureus ATCC 25923 c th to ra vng c ch kp (hai vng c ch c to ra). c c kt qu QC chnh xc, s dng S. aureus ATCC 29213 (khng c vng c ch kp) vi gii hn chp nhn l 33-39 mm.

M100-S21 Bng 3B. Gii hn cho php i vi cc chng kim tra cht lng dng trong kim sot chnh xc ca phng php khoanh giy khuch tn ca cc chng kh nui cy

Khng sinh Amoxicillin-clavulanic axitb Ampicillin Ampicillin-sulbactam Azithromycin Aztreonam Cefaclor Cefdinir Cefditoren Cefepime Cefetamet Cefixime Cefmetazole Cefonicid Cefotaxime Cefotetan Cefoxitin Cefpodoxime Cefprozil Ceftaroline Ceftazidime Ceftibuten Ceftizoxime Ceftobiprolec Ceftriaxone Cefuroxime Cephalothin Chloramphenicol

Hm lng 20/10 g 10 g 10/10 g 15 g 30 g 30 g 5 g 5 g 30 g 10 g 5 g 30 g 30 g 30 g 30 g 30 g 10 g 30 g 30 g 30 g 30 g 30 g 30 g 30 g 30 g 30 g 30 g

Haemophilus influenzae ATCC 49247 15-23 13-21 14-22 13-21 30-38 25-34 25-31 23-28 25-33 16-21 31-39 25-31 29-39 27-35 29-36 29-39 28-36 31-39 31-40

Haemophilus influenzae ATCC 49766 25-31 24-31 30-38 20-27 30-38 28-36 -

Neisseria gonorrhoeae ATCC49226 40-49 37-46 35-43 37^5 31-36 38-48 30-36 33-41 35-43 35-43 42-51 39-51 33-41 -

Streptococcus pneumoniae ATCC 49619a 30-36 19-25 24-32 26-31 27-35 28-35 16-23 31-39 28-34 25-32 31-41 28-34 33-39 30-35 26-32 23-27

Ciprofloxacin Clarithromycin Clinafloxacin Clindamycin Daptomycind Dirithromycin Doripenem Enoxacin Ertapenem Erythromycin Faropenem Fleroxacin Garenoxacin Gatifloxacin Gemifloxacin Grepafloxacin Iclaprim Imipenem Levofloxacin Linezolid Lomefloxacin Loracarbef Meropenem Moxifloxacin Nitrofurantoin Norfloxacin Ofloxacin Oxacillin Penicillin Piperacillin-tazobactam Quinupristin-dalfopristin Razupenem Rifampin

5 g 15 g 5 g 2 g 30 g 15 g 10 g 10 g 10 g 15 g 5 g 5 g 5 g 5 g 5 g 5 g 5 g 10 g 5 g 30 g 10 g 30 g 10 g 5 g 300 g 10 g 5 g 1 g 10 n v 100/10 g 15 g 10 g 5 g

34-42 11-17 34-43 21-31 20-28 15-22 30-38 33-41 33-41 30-37 32-39 24-33 21-29 32-40 33-41 20-28 31-39 31-40 33-38 15-21 24-30 22-30

27-33 26-32 -

48-58 43-51 43-51 45-56 44-52 45-54 43-51 26-34 -

M100-S21 25-31 27-34 19-25 19-26 18-25 30-38 28-35 25-30 27-35 26-33 24-31 28-34 21-28 21-29 20-25 25-34 22-28 28-35 25-31 23-29 15-21 16-21 <12e 24-30 19-24 29-36 25-30

M100-S21 Bng 3B (Tip) Haemophilus influenzae ATCC 49247a 32-40 17-23 14-22 23-31 24-32 22-29 32-39 Haemophilus influenzae ATCC 49766 Neisseria gonorrhoeae ATCC49226 43-51 23-29 30-42 30-40 28-35 42-55 Streptococcus pneumoniae ATCC 49619b 21-27 17-24 27-33 27-31 23-29 20-28 25-32 20-27

Khng sinh Sparfloxacin Spectinomycin Telavancin Telithromycin Tetracycline Tigecycline Trimethoprim-sulfamethoxazole Trospectomycin Trovafloxacin Vancomycin

Hm lng 5 g 100 g 30 g 15 g 30 g 15 g 1.25/23.75 g 30 g 10 g 30 g

Cc iu kin th nghim khoanh giy khuch tn i vi cc chng phn lp t lm sng v tin hnh kim sot cht lng Haemophilus influenzae Neisseria gonorrhoeae Streptococci v Neisseria meningitidis

Chng

Mi trng

Mi trng th nghim cho Haemophilus (HTM) Trc tip t khun lc 5% C02; 16 - 18 h; 35 C

Thch GC base v 1 % yu t kch thch tng trng thch hp. Khng yu cu s dng MHA b sung 5% mu cu loi b t huyt cht kch thch tng trng phi cystein i vi phng php khoanh giy khuch tn. Trc tip t khun lc 5% C02; 20 - 24 h; 35 C Trc tip t khun lc 5% C02; 20 to 24 h; 35 oC

Huyn dch vi khun iu kin nui cy

Vit tt: HTM, mi trng th nghim Haemophilus; MHA, thch Mueller-Hinton LU : Cc thng tin c in m l mi hoc c hiu chnh so vi phin bn trc Lu

M100-S21 a) Mc d thiu mt tiu chun din gii kt qu khoanh giy khuch tn cho S. pneumonia vi tng nhm -lactama, Streptococcus pneumoniae ATCC49619 l chng c ch nh cho kim sot cht lng tt c cc th nghim khoanh giy khuch tn i vi Streptococcus spp. b) Khi th nghim Haemophilus trn mi trng HTM, cc gii hn cho php i vi chng kim tra cht lng E. coli ATCC 35218 l 17 n 22 mm i vi amoxicillin-clavulanic axit khi iu kin hiu kh. c) H. influenzae ATCC 49247 hoc 49766 c th s dng trong kim sot cht lng thng qui. d) Mt s l thch Mueller-Hinton thiu calcium v to vng c ch nh. e) kim tra cht lng khoanh giy khng sinh oxacillin s dng chng chun Staphylococcus aureus ATCC 25923, vi ng knh vng c ch chp nhn c l 18-24mm.

M100-S21 Bng 3C. Khoanh giy khuch tn: Hng dn tham kho v tn sut th nghim kim tra cht lng Bng ny tm tt cc xut v tn sut cho vic kim tra cht lng thng qui khi s dng cc chng chun ATCC khuyn co bi CLSI i vi cc th nghim tnh nhy cm khng sinh (AST). Ch p dng i vi cc khng sinh cn th 20-30 ngy cho tha mn kt qu mong i. S ngy lin tip cn tin hnh th nghim QCa 1 5 20 hoc 30 X X X X X V d: Chuyn vic iu chnh c bng mt thng sang phng php o c bng thit bc hng dn kim sot cht lng ca hng.

iu chnh th nghim Khoanh giy khng sinh S dng cho mt l hng mi S dng cho nh sn xut mi Mi trng (a thch c chun b) S dng cho mt l hng mi S dng cho nh sn xut mi Chun b huyn dch vi khun S dng cc phng php chun b huyn dch vi khun/chun ha thit b o c c hng dn kim sot cht lng ring

Lu

Chuyn vic chun b huyn dch vi khun/chun ha mt phng php ph thuc vo k thut ca ngi tin hnh.

M100-S21 V d: Chuyn vic iu chnh c bng mt thng sang mt phng php khc m khng dng thit b o c.

o vng c ch Thay i phng php o ng knh vng c ch

V d: Thay v phng php o ng knh vng c ch thng thng bng mt thng sang dng my o t ng. Ngoi ra, tin hnh cc nghin cu t nh gi.

Thit b/phn mm (v d, my c ng knh vng c ch t ng) Cc phn mm cp nht nh hng n kt qu AST X Kim sot tt c cc thuc, khng ch nhng thuc lin quan trong vic iu chnh phn mm.

Sa cha thit b nh hng n kt qu AST

M100-S21 Ph thuc vo vic sa cha (v d: cc b phn quan trng nh thit b o c) c th cn tin hnh cc th nghim b sung (v d, nm ngy).

LU 1: Khi c thm bt k khng sinh MI no, cn th nghim kim sot cht lng 20-30 ngy lin tc tha mn iu kin th nghim (xem M02A10, Phn15.7) trc khi s dng. LU 2: QC c th tin hnh trc hoc ng thi vi cc th nghim trn chng bnh phm. Kt qu ca bnh phm c th c bo co trong ngy nu kt qu kim tra cht lng nm trong gii hn cho php. LU 3: Cn tun th cc hng dn v qui nh ca nh sn xut cng nh nhng quy nh ca tng ca tng labo. LU 4: i vi cc trng hp kt qu nm ngoi gii hn, tham kho M02-A10, Phn 15.8. LU 5: Canh thang v nc mui sinh l pha huyn dch vi khun khng cn kim tra cht lng thng qui. Lu a. Khng c b qua vic kim tra cht lng thng qui hng tun hoc hng ngy.

M100-S21 Bng 3D. Khoanh giy khuch tn: Hng dn x l cc vn v kim sot cht lng Bng ny cung cp cc hng dn x l s c cc trng hp kim sot cht lng nm ngoi gii hn cho php ca cc th nghim nhy cm khng sinh s dng mi trng thch Mueller-Hinton. c thm thng tin chi tit tham kho M02-A10, Phn 15 v Qun l Cht lng v Qun l m bo Quy trnh. Cc trng hp kt qu th nghim nm ngoi gii hn cho php, trc ht, cn phi tin hnh li th nghim khng sinh . Nu vn khng c khc phc, hng dn x l s c ny cung cp mt s bin php b sung cho cc trng hp kt qu ca th nghim kim sot cht lng nm ngoi gii hn, Ngoi ra, nu vn khng gii quyt c vn , cn thng bo cho nh sn xut v cc vn ca sn phm. Lu chung (1) Duy tr chng QC: trnh cy chuyn nhiu ln. Cy chuyn chng QC mi t dng stock sang ng d tr. Nu s dng chng ng kh, tun th hng dn ca nh sn xut. Gi chng gc E. coli ATCCa 35218 v K. pneumoniae ATCC 700603 -60 C hoc thp hn v chun b chng dng chia nh cho s dng hng tun. Khng sinh Aminoglycosides Chng kim tra cht lng Bt k Quan st Vng c ch qu nh Nguyn nhn c th pH mi trng qu thp Bn lun/Hnh ng Khong pH cho php = 7.2-7.4. Trnh C02 v lm gim pH Khong pH cho php = 7.2-7.4 S dng l mi trng mi thay th S dng l mi trng mi thay th S dng l khoanh giy khng sinh mi. Kim tra iu kin bo qun v ton b bao gi.

Aminoglycosides Aminoglycosides Aminoglycosides Amoxicillin-clavulanic axit

Bt k P. aeruginosa ATCC 27853 P. aeruginosa ATCC 27853 E. coil ATCC 35218

Vng c ch qu ln Vng c ch qu nh Vng c ch qu ln Vng c ch qu nh

pH mi trng qu cao Ca++ v/hoc Mg++ qu cao Ca++ v/hoc Mg++ qu thp Axit clavulanic b bin tnh. Khoanh giy mt hiu lc.

Ampicillin

E. coli ATCC 35218

Vng c ch qu ln

Mt plasmid m ha enzyme beta-lactamase

M100-S21 Xem lu (1) v duy tr chng kim tra cht lng QC.

Nhm Beta-lactam

Bt k

Ban u vng c ch c th chp nhn c nhng sau b gim v c th nm ngoi gii hn.

Khoanh giy khng sinh mt S dng l khoanh hiu lc giy mi. Kim tra iu kin bo qun v ton b bao gi. Imipenem, axit clavulanic, v cefaclor l cc khng sinh d b bin tnh. Mt plasmid m ha enzyme beta-lactamase Xem bn lun (1) v duy tr chng kim tra cht lng QC.

Aztreonam Cefotaxime Cefpodoxime Ceftazidime Ceftriaxone Cefotaxime/clavulanic axit Ceftazidime/clavulanic axit

K. pneumoniae ATCC 700603

Vng c ch qu rng

K. pneumoniae ATCC 700603

Xt nghim khng nh Mt plasmid m ha enzyme Xem bn lun (1) v duy ESBL m tnh beta-lactamase tr chng kim tra cht lng QC. Vng c ch qu rng pH mi trng qu thp Khong pH cho php = 7.2-7.4. Trnh trong iu kin CO2, thng to pH thp hn. Khong pH cho php = 7.2-7.4

Penicillins

Bt k

Penicillins

Bt k

Vng c ch qu nh

pH mi trng qu cao

Carbenicillin

P. aeruginosa ATCC 27853

Vng qu nh

Cc chng QC tr nn khng thuc sau khi cy chuyn nhiu ln. Axit clavulanic b bin tnh. Khoanh giy mt hiu lc. pH mi trng qu thp

M100-S21 Xem bn lun (1) v duy tr chng kim tra cht lng QC. S dng l khoanh giy mi. Kim tra iu kin bo qun v ton b bao gi. Khong pH cho php = 7.2-7.4.. Trnh trong iu kin C0 2, thng to pH thp hn. Khong pH cho php= 7.2-7.4 S dng l mi trng mi thay th Khong pH cho php = 7.2-7.4. Trnh trong iu kin CO2 , thng to pH thp hn. Khong pH cho php = 7.2-7.4

Ticarcillin-clavulanic axit

E. coli ATCC 35218

Vng c ch qu nh

Clindamycin

S. aureus ATCC 25923

Vng c ch qu nh

Clindamycin

S. aureus ATCC 25923

Vng c ch qu rng

pH mi trng qu cao

Daptomycin Macrolides

S. aureus ATCC 25923 S. aureus ATCC 25923

Vng c ch qu nh Vng c ch qu nh

Ca++ trong mi trng qu thp pH mi trng qu thp

Macrolides

S. aureus ATCC 25923

Vng c ch qu rng

pH mi trng qu cao

M100-S21 Bng 3D. (Tip) Khng sinh Quinolones Chng kim tra cht lng Bt k Quan st Vng c ch qu nh Nguyn nhn c th pH mi trng qu thp Bn lun/Hnh ng Khong pH cho php = 7.2-7.4. Trnh C0 2, thng cho pH thp hn Khong pH cho php = 7.2-7.4 Khong pH cho php = 7.2-7.4. Trnh C0 2, thng cho pH thp Khong pH cho php = 7.2-7.4 S dng l mi trng mi thay th.

Quinolones Tetracyclines

Bt k Bt k

Vng c ch qu ln Vng c ch qu ln

pH mi trng qu cao pH mi trng qu thp pH mi trng qu cao Hm lng Ca++ v/hoc Mg++ qu cao.

Tetracyclines Tetracyclines

Bt k Bt k

Vng c ch qu nh Vng qu nh

Tetracyclines

Bt k

Vng qu ln

Hm lng Ca++ v/hoc Mg++ qu thp.

S dng l mi trng mi mi thay th.

Sulfonamides Trimethoprim Trimethoprimsulfamethoxazole

E. faecalis ATCC 29212

Vng c ch 20 mm

Mi trng cha thymidine S dng l mi hm lng qu cao. trng mi thay th.

Nhiu loi

Bt k

Nhiu vng c ch qu rng

Huyn dch vi khun qu long Li trong chun b huyn dch vi khun Mi trng qu mng Mi trng MHA khng m bo v dinh dng.

M100-S21 Pha li s dng c chun 0.5 McFarland hoc thit b o c tiu chun ha khc. Kim tra hn dng v iu kin bo qun nu dng bari sulfate S dng a thch c dy 4mm Kim tra l MHA thay th Pha li s dng c chun 0.5 McFarland hoc thit b o c tiu chun ha khc. Kim tra hn dng v iu kin bo qun nu dng bari sulfate S dng a thch c dy 4mm Kim tra l MHA thay th Kim tra bc c i vi li o c v li ghi kt qu. Xt nghim li. Nu kt qu xt nghim li nm ngoi gii hn v khng c li, tin hnh sa li.

Nhiu loi

Bt k

Nhiu vng c ch qu nh

Huyn dch vi khun qu m c. Li chun b huyn dch vi khun. mi trng qu dy. Mi trng MHA khng m bo v dinh dng

Nhiu loi

Bt k

Mt hoc nhiu vng c Li o c ng knh ch qu nh hoc qu vng c ch. ln Li ghi kt qu Khoanh giy km cht lng ngu nhin Khoanh giy khng c p hon ton vo b mt thch

Nhiu loi

S. pneumoniae ATCC 49619

Vng qu ln. Khun lc khng c dn u

Khun lc cy chuyn qu c hoc cha nhiu vi khun khng hot ng (ng-nonviable). a cy chuyn ch nn t 18-20h.

M100-S21 Cy chuyn chng chun v lp li xt nghim QC hoc pha chng chun t ng d tr chng QC

Nhiu loi

Bt k

Mt chng QC ngoi gii S dng mt chng QC c hn, nhng cc chng th l tt hn cho vic xc khc nm trong vi cng nhli v QC mt loi khng sinh

Kim tra li chng ny khng nh kt qu lp li. nh gi chng thay th vi cc MIC bit. Tin hnh bc sa li vi vn chng QC/khng sinh

S dng l khoanh khng sinh thay th. Kim tra iu kin bo qun v ton b bao gi Nhiu loi Bt k Cc vng b chng ln Qu nhiu khoanh khng Khng qu 12 khoanh nhau sinh trn mt a khng sinh trn a 150mm v khng qu 5 khoanh khng sinh trn i 100mm; i vi mt s vi khun kh mc c th cho vng c ch ln hn th s khoanh khng sinh Vit tt: ESBL, khng betalactama ph rng; MHA, thch Mueller-Hinton; MIC, nng c ch ti thiu; QC, kim sot cht lng. cng t hn.

Nhiu loi

Bt k

Hai chng QC nm ngoi Vn v khoanh khng gii hn vi cng mt sinh khng sinh

M100-S21 Bng 4A. MIC: Gii hn cho php i vi cc chng chun kim tra cht lng c s dng m bo tnh chnh xcvi cc chng d nui cy (Mi trng Mueller-Hinton khng b sung mu hoc cc cht dinh dng [ iu chnh cation vi canh thang]) Staphylococcus aureus ATCC 29213a 1-4 0.12/0.06-0.5/0.25 0.5-2 0.5-2 2-8 0.015-0.06 2-8 1-4 0.25-1 0.25-1 0.12-0.5 0.25-2 1-4 8-32 0.5-2 1^ 1-4 1-4 4-16 1-4 1-8 0.25-1 0.12-0.5 4-16 2-8 Enterococcus faecalis ATCC 29212 64-256 0.25/0.12-1.0/0.5 0.5-2 1-4 0.06-0.25 16-64 0,25-2 d Escherichia coli ATCC 25922 0.5-4 2/1-8/4 2-8 2/1-8/4 8-32 0.06-0.25 0.06-0.25 4-16 1-4 0.25-1 1-4 0.12-0.5 0.12-1 0.015-0.12 0.25-1 0.25-1 0.25-1 0.25-1 0.12-0.5 0.03-0.12 0.06-0.25 2-8 0.25-1 1-4 0.03-0.12 0.06-0.5 0.12-0.5 0.03-0.12 Pseudomonas aeruginosa ATCC 27853 1-4 2-8 2-8 1-4 16-64 1-8 >32 2-8 8-32 1-4 16-64 Escherichia coli ATCC 35218 b,c 4/2-16/8 8/4-32/16 -

Khng sinh Amikacin Amoxicillin-clavulanic axit Ampicillin Ampicillin-sulbactam Azithromycin Azlocillin Aztreonam Besifloxacin Carbenicillin Cefaclor Cefamandole Cefazolin Cefdinir Cefditoren Cefepime Cefetamet Cefixime Cefmetazole Cefonicid Cefoperazone Cefotaxime Cefotetan Cefoxitin Cefpodoxime Cefprozil Ceftaroline Ceftazidime Ceftibuten Ceftizoxime

M100-S21 Ceftobiprole Ceftriaxone Cefuraxime Cephalothin Chloramphenicol Cinoxacin Ciprofloxacine Clarithromycin Clinafloxacin Clindamycinf Colistin Dalbavancine Daptomycinf Dirithromycin Doripenem Doxycycline Enoxacin Ertapenem Erythromycind Faropenem Fidaxomicin Fleroxacin Fosfomycini Garenoxacin Gatifloxacin Gemifloxacin Gentamicinj Grepafloxacin Iclaprim Imipenem Kanamycin Levofloxacin Linezolid Lomefloxacin 0.25-1 1-8 0.5-2 0.12-0.5 2-16 0.12-0.5 0.12-0.5 0.008-0.06 0.06-0.25 0.03-0.12 0.12-1 1-4 0.015-0.06 0.12-0.5 0.5-2 0.06-0.25 0.25-1 0.03-0.12 2-16 0.25-1 0.5-4 0.004-0.03 0.03-0.12 0.008-0.03 0.12-1 0.03-0.12 0.06-0.25 0.015-0.06 1-4 0.06-0.5 1-4 0.25-2 0.06-0.5 4-16 0.25-2 0.03-0.25 4-16 0.03-0.12 1-4 1-4 2-8 2-16 4-16 1-4 1-4 2-8 32-128 0.03-0.25 0.12-1.0 0.015-0.12 4-16 0.12-0.5 0.004-0.03 0.5-2 16-64 0.25-2 1-4 2-8 0.03-0.12 0.03-0.12 2-8 4-16 2-8 2-8 0.004-0.015 0.002-0.015 0.5-2 0.015-0.06 0.5-2 0.06-0.25 0.004-0.015 0.25-1 0.03-0.12 0.5-2 0.004-0.03 0.008-0.03 0.004-0.015 0.25-1 0.004-0.03 1-4 0.06-0.25 1-4 0.008-0.06 0.03-0.12 1-4 8-64 0.25-1 0.06-0.5 0.5-4 0.12-0.5 2-8 2-8 1-4 2-8 0.5-2 0.5-2 0.25-1 0.5-2 0.25-2.0 1-4 0.5-4 1-4 -

M100-S21 Bng 4A. (Tip) Khng sinh Staphylococcus aureus ATCC 29213a 0.5-2 0.03-0.12 0.5-2 1-4 0.06-0.5 4-16 0.015-0.12 0.12-0.5 <0.25 8-32 0.5-2 0.12-1 0.015-0.12 0.12-0.5 0.25-2 1-4 0.25/4-2/4 0.25-1 0.008-0.03 0.004-0.015 0.03-0.12 32-128 0.015-0.12 Enterococcus faecalis ATCC 9212 2-8 >16 1-4 1-4 0.06-0.5 2-8 4-16 4-16 2-8 1-4 0.008-0.03 8-32 1-4 1-4 -4/4 2-8 0.25-1 0.5-4 0.12-0.5 32-128 2-8 Escherichia coli ATCC 25922 0.5-2 0.03-0.251 0.008-0.06 2-8 0.25-1 0.12-0.5 0.008-0.06 1-4 < 0.5-1 4-16 0.03-0.12 0.015-0.12 1-4 1/4-4/4 0.25-2 0.06-0.5 4-16 0.004-0.015 8-32 0.015-0.06 Pseudomonas aeruginosa ATCC 27853 >8 0.25-1 8-32 8-32 1-8 0.5-8 1-4 1-8 1-8 1/4-8/4 0.25-2 16-64 0.5-2 Escherichia coli ATCC 35218b 0.5/4-2/4 -

Loracarbef Mecillinam Meropenem Methicillin Mezlocillin Minocyclinee Moxalactam Moxifloxacin Nafcillin Nalidixic axite Netilmicin Nitrofurantoin Norfloxacin Ofloxacin Oritavancing Oxacillin Penicillin Piperacillin Piperacillin-tazobactam Polymyxin B Quinupristin-dalfopristin Razupenem Rifampin Sparfloxacin Sulfisoxazolee,m Sulopenem

M100-S21 Teicoplanin Telavancin Telithromycin Tetracycline Ticarcillin Ticarcillin-clavulanic axit Tigecyclineo Tobramycin Trimethoprimm Trimethoprimsulfamethoxazole Trospectomycin Trovafloxacin Ulifloxacin (prulifloxacin)l Vancomycinp 0.25-1 0.12-1 0.06-0.25 0.12-1 2-8 0.5/2-2/2 0.03-0.25 0.12-1 1-4 < 0.5/9.5 2-16 0.008-0.03 0.5-2 0.25-1 0.12-0.5 0.015-0.12 8-32 16-64 16/2-64/2 0.03-0.12 8-32 0.12-0.5 < 0.5/9.5 2-8 0.06-0.25 1-4 0.5-2 4-16 4/2-16/2 0.03-0.25 0.25-1 0.5-2 < 0.5/9.5 8-32 0.004-0.015 0.004-0.015 8-32 8-32 8/2-32/2 0.25-1 >64 8/152-32/608 0.25-2 0.12-0.5 8/2-32/2k -

Vit tt: AST, th nghim tnh nhy cm khng sinh (khng sinh ); HTM, mi trng th nghim cho Haemopilus; LHB, mu nga ly gii; MHB, canh thang Mueller-Hinton. LU 1: Cc gi tr MIC ny thu c t mt s phng xt nghim tham chiu (phng xt nghim chun thc) bng cc phng php vi pha long. Nu bn hoc t hn 4 nng c th nghim, vic kim sot cht lng c th kh khn hn. LU 2: Thng tin in m l mi hoc c iu ch so vi phin bn trc. Lu ATCC l tn thng mi ca h thng chng chun theo tiu chun ca M. Yu cu cy chuyn v gi chng cn thn v cc chng ny c th mt plasmid; tham kho ti liu M07-A8, Phn 16.4. Chng chun c khuyn co s dng khi tin hnh th nghim vi khng sinh phc hp betalactam/khng betalactamase Chng ny ch c coi nh l chng chun b sung v khng cn thit phi tin hnh th nghim kim tra cht lng thng quy Gii hn kim tra cht lng i ca E. coli ATCC 25922 vi ciprofloxacin, nalidixic axit, minocycline, v sulfisoxazole khi th nghim trong mi trng CAMHB b sung 2.5 n 5% mu nga ly gii, trong iu kin hiu kh hoc 5% CO2 (khi th nghim vi N. meningitides) ging vi th nghim c m t trong Bng 4A. f. Khi erythromycin v clindamycin cng mt ging pht hin khng clindamycin do khch thch, S. aureus ATCC BAA-977 (khng qua trung gian ermA) v S. aureus ATCCBAA-976 (c ch khng qua bm y macrolide qua trung gian msrA) l cc chng chun c xut s dng vi mc ch nh gi cht lng. S. aureus ATCCBAA-977 th hin tnh khng vi clindamycin do kch thch (pht trin c trong ging), trong khi S. aureus ATCC 29213 v S. aureus ATCC BAA-976 khng th hin tnh khng clindamycin do kch thch (khng pht trin trong ging). a. b. c. d. e.

M100-S21 g. Nhng gii hn QC phn nh cc gi tr ca MIC thu c khi s dng mi trng canh thang Mueller-Hinton c b sung 0.002% polysorbate 80. h. Nhng gii hn QC phn nh cc gi tr MIC thu c khi s dng mi trng canh thang Mueller-Hinton c b sung canxi t nng cui cng l 50 g/mL. Phng php pha long trn thch khng c gi tr vi daptomycin. i. Phng php xc nh MIC c ph duyt l pha long trn thch. Mi trng thch cn b sung 25 g/mL glucose-6-phosphate. Khng nn tin hnh th nghim pha long trong mi trng canh thang. j. i vi cc chng chun cho th nghim sng lc khng aminoglycoside mc cao i vi Enterococci, xem Bng 2D-S6 cui Bng 2D. k. Th nghim ny ch nn tin hnh bng pha long trn thch. l. Ulifloxacin l cht chuyn ha c hot tnh ca khng sinh ang th nghim (cha c chp thun) prulifloxacin. Ch s dng ulifloxacin trong xt nghim tnh nhy cm khng sinh m. Th nghim rt ph thuc cht lng mi trng, c bit l i vi Enterococci n. Cc gii hn kim tra cht lng i vi E. coli ATCC 35218 khi s dng mi trng th nghim Haemophilus (HTM) l 16/2 n 64/2 g/mL. o. i vi th nghim vi pha long ca tigecycline, khi cc bc MIC c chun b, mi trng phi c chun b mi trong ngy s dng. Mi trng khng qu 12h tnh t lc cc bc MIC c chun b; tuy nhin cc panel c th gi ng lnh cho ln s dng tip theo. p. i vi cc chng chun th nghim sng lc vancomycin ca cc chng Enterococci, xem Bng 2D-S6 cui Bng 2D.

M100-S21 Bng 4B. Gii hn cho php i vi cc chng kim tra cht lng c s dng kim tra s chnh xc ca nng c ch ti thiu (g/mL) ca cc chng kh mc (Pha long trn canh thang) Haemophilus influenzae ATCC 49247 2/1-16/8 2-8 2/1-8/4 1-4 0.12-0.5 0.015-0.06 0.06-0.25 0.5-2 0.5-2 0.12-1 2-16 0.12-0.5 0.25-1 0.25-1 0.03-0.12 0.12-1 0.25-1 0.06-0.5 0.12-1 0.06-0.25 Haemophilus influenzae ATCC 49766 1-4 0.25-1 0.12-0.5 0.06-0.25 1-4 0.016-0.06 0.25-1 Sfreptococcus pneumoniae ATCC 49619 0.03-0.12 0.03/0.015-0.12/0.06 0.06-0.25 0.06-0.25 0.03-0.12 1-4 0.03-0.25 0.015-0.12 0.03-0.25 0.5-2 0.03-0.12 0.03-0.12 0.25-1 0.008-0.03 0.12-0.5 0.004-0.03 0.03-0.12 0.25-1

Khng sinh Amoxicillina Amoxicillin-clavulanic axita Ampicillin Ampicillin- sulbactam Azithromycin Aztreonam Besifloxacin Cefaclor Cefamandole Cefdinir Cefditoren Cefepime Cefetamet Cefixime Cefmetazole Cefonicid Cefotaxime Cefotetan Cefoxitin Cefpirome Cefpodoxime Cefprozil Ceftaroline Ceftazidime Ceftibuten Ceftizoxime Ceftobiproleb Ceftriaxone Cefuroxime

M100-S21 Cephalothin Chloramphenicol Ciprofloxacinc Clarithromycin Clinafloxacin Clindamycin Dalbavancind Daptomycine Dirithromycin Doripenem Doxycycline Enoxacin Ertapenem Erythromycin Faropenem Fleroxacin Garenoxacin Gatifloxacin Gemifloxacin Gentamicin Grepafloxacin Iclaprim Imipenem Levofloxacin Linezolid Lomefloxacin Loracarbef Meropenem Metronidazole Moxifloxacin Nalidixic axitc 0.25-1 0.004-0.03 4-16 0.001-0.008 8-32 0.03-0.12 0.002-0.008 0.004-0.03 0.002-0.008 0.002-0.015 0.12-1 0.008-0.03 0.03-0.12 0.008-0.03 0.06-0.25 0.015-0.06 0.12-0.5 0.25-1 0.5-2 0.03-0.12 0.5-2 2-8 0.03-0.12 0.03-0.12 0.03-0.12 0.008-0.03 0.06-0.5 0.06-0.25 0.03-0.12 0.015-0.12 0.03-0.25 0.03-0.12 0.03-0.25 0.015-0.06 0.12-0.5 0.008-0.03 0.06-0.5 0.03-0.12 0.03-0.12 0.5-2 0.25-2 2-8 0.06-0.25 0.06-0.25 -

M100-S21 Bng 4B. (Tip) Haemophilus influenzae ATCC 49247a 0.015-0.06 0.06/4-0.5/4 2-8 0.25-1 0.004-0.015 1-4 4-32 0.06-0.5 0.03/0.590.25/4.75 0.5-2 0.004-0.015 Haemophilus influenzae ATCC 49766 0.008-0.03 Sfreptococcus pneumoniae ATCC 49619 4-16 2-8 1-4 0.001-0.004 0.25-1 0.25-1 0.008-0.06 0.015-0.06 0.12-0.5 0.004-0.03 0.004-0.03 0.06-0.5 0.015-0.12 0.12/2.41/19 1-4 0.06-0.25 0.12-0.5

Khng sinh Nitrofurantoin Norfloxacin Ofloxacin Oritavancind Penicillin Piperacillin-tazobactam Quinupristin-dalfopristin Razupenem Rifampin Sparfloxacin Spectinomycin Telavancin Telithromycin Tetracycline Tigecyclinef Trimethoprimsulfamethoxazole Trospectomycin Trovafloxacin Vancomycin

M100-S21 Chng vi khun Mi trng Cc iu kin th nghim i vi cc chng bnh phm v chng chun kim tra cht lng Haemophilus influenzae Streptococcus pneumoniae v Neisseria menigitidis Streptococci, Canh thang pha long: Canh thang Canh thang pha long: Canh thang Canh thang pha long: Canh thang th nghim Mueller-Hinton iu chnh Mueller-Hinton iu chnh cation vi Haemophilus (HTM) cation vi mu nga ly gii (2.5mu nga ly gii (2.5-5% v/v) 5% v/v) Pha trc tip t khun lc Pha trc tip t khun lc Pha trc tip t khun lc

Huyn dch vi khun

iu kin nui cy

35 C; hiu kh; 20-24 hours

35 C; hiu kh; 20-24 hours

5% CO2; 20-24 gi; 35 oC (Chng chun S. pneumoniae ATCC 49619, 5% CO2 hoc hiu kh, ngoi tr vi azithromycin ch duy nht iu kin hiu kh)

Vit tt: CAMHB, canh thang Mueller-Hinton iu chnh cation; HTM, mi trng th nghim cho Haemopilus; LHB, mu nga ly gii; MHB, canh thang Mueller-Hinton; MIC, nng c ch ti thiu. LU 1: Thng tin in m l mi v iu chnh so vi phin bn trc LU 2: i vi cc gii hn pha long 4 ln, cc kt qu nu cch xa gii hn cho php th nn kim tra li. nh gi hiu lc kim tra cht lng vi d liu t cc chng kim tra cht lng khc. Ghi ch a. Gii hn kim sot cht lng vi E. coli ATCC 35218 khi th nghim trn HTM l 4/2 n 16/8 g/mL i vi amoxicillin-clavulanic axit v 256 g/mL i vi amoxicillin; th nghim vi amoxicillin c th gip khng nh cc chng vn duy tr c kh nng sinh enzyme -lactamase. b. S dng H. influenzae ATCC 49247 hoc 49766 i vi th nghim kim tra cht lng thng qui. c. Gii hn kim tra cht lng i vi E. coli ATCC 25922 vi ciprofloxacin, nalidixic axit, minocycline, v sulfisoxazole khi th nghim trn mi trng CAMHB vi 2.5-5% mu nga ly gii, nui cy iu kin hiu kh hoc 5% CO2 (vi th nghim cho N. meningitides) ging nh lit k trong Bng 4A. d. Gii hn QC phn nh MIC t c khi mi trng canh thang Mueller-Hinton c b sung 0.002% polysorbate 80. e. Gii hn QC phn nh MICs t c khi mi trng canh thang Mueller-Hinton c b sung canxi t nng cui 50 g/mL. Pha long trn thch khng hiu lc i vi daptomycin. f. i vi th nghim vi pha long ca tigecycline, khi cc bc MIC c chun b, mi trng phi c chun b mi trong ngy s dng. Mi trng khng qu 12h tnh t lc cc bc nng c chun b; tuy nhin cc panel c th gi ng lnh cho ln s dng tip theo.

M100-S21 Bng 4C. Gii hn cho php i vi cc chng kim tra cht lng s dng kim tra chnh xc ca cc nng c ch ti thiu (MICs) (g/mL) ca Neisseria gonorrhoeae bng phng php pha long trn thch Neisseria gonorrhoeae ATCC 49226 a 0.008-0.03 0.015-0.06 0.015-0.25 0.004-0.03 0.5-2 0.015-0.06 0.5-2 0.5-2 0.03-0.12 0.03-0.12 0.008-0.03 0.004-0.015 0.25-1 0.001-0.008 0.015-0.06 0.008-0.03 0.002-0.015 0.004-0.03 0.008-0.03 0.008-0.03 0.004-0.015 0.25-1

Khng sinh Amoxicillin Cefdinir Cefepime Cefetamet Cefixime Cefmetazole Cefotaxime Cefotetan Cefoxitin Cefpodoxime Ceftazidime Ceftizoxime Ceftriaxone Cefuroxime Ciprofloxacin Clarithromycin Doxycycline Enoxacin Erythromycin Fleroxacin Gatifloxacin Gentamicin Grepafloxacin Lomefloxacin Meropenem Metronidazole Moxifloxacin Ofloxacin Penicillin

M100-S21 Sparfloxacin Spectinomycin Telithromycin Tetracycline Traspectomycin Trovafloxacin 0.004-0.015 8-32 0.25-1 1-4 0.004-0.015

Cc iu kin th nghim i vi cc chng bnh phm v chng chun kim tra cht lng Chng vi khun Mi trng Neisseria gonorrhoeae Pha long trn thch: thch GC c bn v 1% yu t kch thch tng trng. S dng cht b tr phi cystein i vi phng php pha long trn thch vi carbapenems v clavulanate. Yu t kch thch cha cysteine khng thay i mt cch ng k kt qu th nghim pha long vi cc loi khng sinh khc.

Huyn dch vi khun

Pha trc tip t khun lc, t c tng ng c chun 0.5 McFarland

iu kin nui cy

36 1o C (khng vt qu 37 C); 5% C0 2; 20-24 gi

LU 1: Thng tin in m lm mi v iu chnh so vi phin bn trc. LU 2: i vi cc gii hn pha long 4 ln, cc kt qu nu cch xa gii hn cho php th nn kim tra li. nh gi hiu lc kim tra cht lng vi d liu t cc chng kim tra cht lng khc.

M100-S21 Bng 4D. MIC: Gii gii hn cho cc chng kim sot cht lng i vi cc vi khun k kh (phng php pha long trn thch) Clostridium Bacteroides Eubacterium Bacteroides difficle Khng Sinh fragilis lentum ATCC thetaiotaomicron ATCC ATCC 25285 43055a ATCC 29714 700057 Amoxicillin-clavulanic 0.25/0.125 0.25/0.125 NRa, b 0.5/0.252/1 acid (2:1) 1/0.5 1/0.5 Ampicilin 16-64 16-64 1-4 _b Ampicillin-sulbactam 0.5/0.254/2 0.5/0.252/1 0,5/0,25-2/1 0.25/0.1252/1 (2:1) b Cefmetazole 832 32-128 _ 4-16 Cefoperazone 32-128 32-128 _b 32-128 Cefotaxime 8-32 16-64 _b 64-256 b Cefotetam 4-16 32-128 _ 32128 Cefoxitin 4-16 8-32 _b 4-16 Ceftizoxime NRa 4-16 _b 16-64 Ceftriaxone 32-128 64-256 _b NRa Chloramphenicol 28 416 _b _b b Clinafoloxacin 0,03-0,125 0,06-0,5 _ 0.030.125 Clindamycin 0,5-2 2-8 2-8 0,06-0,25 Doripenem _b _b 0,5-4 _b b Ertapenem 0,06-0,25 0,25-1 _ 0,5-2 Faropenem 0,03-0,25 0,12-1 _b 1-4 Fidaxomixin _b _b 0,06-0,25 _b Garenoxacin 0,06-0,5 0,25-1 0,5-2 1-4 Imipenem 0,03-0,125 0,125-0,5 _b 0,125-0,5 Linezolid 2-8 2-8 1-4 0,5-2 Moropenem 0,03-0,25 0,125-0,5 0,5-4 0,125-1 Metronidazole 0,25-1 0,5-2 0,125-0,5 _b b Mezlocillin 16-64 8-32 _ 8-32 Moxifloxacin 0,125-0,5 1-4 1-4 0,125-05 Nitazoxanide _b _b 0,06-0,5 _b Penicillin 8-32 8-32 1-4 _b Piperacillin 2-8 8-32 4-16 8-32

M100-S21 Piperacillin-tazobactam 0,125/4-0,5/4 4/4-16/4 Ramoplanin _b _b Razupenem 0,015-0,12 0,06-0,25 b Rifaximin _ _b Sulopenem _b 0,06-0,5 Tetracycline 0,125-0,5 8-32 Ticarcilin 16-64 16-64 Ticarcillin-clavulanate NRa 0,5/2-2/2 Tygecycline 0,12-1 0,5-2 Tinidazole _b _b b Tizoxanide _ _b b Vancomycin _ _b Vit tt: MIC, Nng c ch ti thiu; QC, kim sot cht lng; Ch 1: Thng tin in m l mi v c s iu chnh so vi phin bn trc Ch 2: n v l microgram trn mililite (g/mL) ngoi tr cho penicillin 4/4-16/4 0,125-0,5 0,06-0,25 0,0039-0,0156 1-4 _b 16-64 16/2-64/2 0,125-1 0,125-0,5 0,06-0,5 0,5-4 4/4-16/4 _b 0,06-05 _b 0,5-2 _b 16-64 16/2-64/2 0,06-0,5 _b _b _b

Ch thch a. NR chng t rng khng c gi tr MIC no c khuyn co vi cc cp vi khun/khng sinh. Trong nhng trng hp c th, nhng n lc xc nh khong gi tr gii hn cho QC chng t rng rt nhiu khong gi tr rng thu c (amoxicillin-clavulanic acid vi E. lentum ATCC 43055; ceftriaxone vi E. lentum ATCC 43055; ceftriaxole vi B. fragilis ATCC 25285; v ticarcillin-clavulanic vi B. fragilis ATCC 25285). Theo nh trn, nhng cp vi khun/khng sinh khng ph hp cho QC. b. K hiu-b chng t rng khng c mt nghin cu no v QC c tin hnh bng cc phng php c khuyn co gn y.

M100-S21

M100-S21 Bng 4E. MIC: Gii gii hn cho cc chng kim sot cht lng (QC) i vi cc vi khun k kh (phng php vi pha long canh thang) Clostridium Eubacterium Khng Sinh Bacteroides Bacteroides difficle ATCC lentum ATCC fragilis thetaiotaomicron 700057 43055 a ATCC 25285 ATCC 29714 c Amoxicillin-clavulanic 0.25/0.125 0.25/0.1251/0.5 _ NRa acid (2:1) 1/0.5 Ampicillin-sulbactam 0.5/0.252/1 0.5/0.252/1 _c 0.5/0.252/1 (2:1) Cefotetan 18 16128 _c 1664 Cefoxitin 28 864 _c 216 NRa _c 832 Ceftizoxime NRa Chloramphenicol 4-16 8-32 _c 4-16 Clindamycin 0,5-2 2-8 _c 0,06-0,25 Doripenem 0,12-0,5 0,12-1 _c NRa Doxyciline 0,12-0,5 2-8 _c 2-16 Ertapenem 0,06-0,5 0,5-2 _c 0,5-4 0,5-2 Faropenem 0,015-0,06 0,12-1 _c c Garenoxacin 0,06-0,25 0,25-2 _ 0,5-2 Imipenem 0,03-0,25 0,25-1 _c 0,25-2 Linezolid 2-8 2-8 _c 0,5-2 Meropenem 0,03-0,25 0,06-0,5 _c 0,125-1 0,125-0,5 Metronidazole 0,25-2 0,5-4 _c 0,12-0,5 Moxifloxacin 0,12-0,5 1,0-8 _c NRa Penicillin 8-32 8-32 _c c Piperacillin 4-8 8-64 _ 8-32 c 8/4-32/4 Piperacillin-tazobactam 0,03/4-0,25/4 2/4-16/4 _ Razupenem 0,03-0,25 0,12-0,5 0,06-0,5 0,12-0,5 Sulopenem NRa 0,03-0,25 0,5-2 0,25-1 Ticarcillin-clavulanate 0,06/2-0,5/2 0,5/2-2/2 _c 8/2-32/2 0,06-0,5 0,25-1 0,03-0,12 NRa Tygecyclineb Vit tt: MIC, Nng c ch ti thiu Ch 1: Nhng thng tin c in m l mi hoc c iu chnh so vi phin bn trc Ch 2: Vi gii pha long bc 4, nhng kt qu ngoi xa gii hn cho php cn phi nghi ng. nh gi li gi tr ca nng khng bng thng tin t cc chng QC khc.

M100-S21 Ch thch a. NR th hin khong gii hn cho php ca cc chng QC cha c xc lp thnh cng mc d c nhiu l lc nghin cu b. i vi th nghim vi pha long ca tigecycline, khi cc bc MIC c chun b, mi trng phi c chun b mi trong ngy s dng. Mi trng khng qu 12h tnh t lc cc bc nng c chun b; tuy nhin cc panel c th gi ng lnh cho ln s dng tip theo. c. K hiu _ th hin rng khng mt nghin cu no tin hnh bi nhng phng php c khuyn co gn y.

M100-S21

M100-S21 Bng 4F. MIC:- Hng dn tham kho v tn sut kim sot cht lng Bng ny tm tt cc xut v tn sut cho vic kim tra cht lng thng qui khi s dng cc chng chun ATCC khuyn co bi CLSI i vi cc th nghim tnh nhy cm khng sinh (AST). Ch p dng i vi cc khng sinh cn th 20-30 ngy cho tha mn kt qu mong i. .

S ngy lin tip cn tin hnh th nghim QCa iu chnh th nghim Th nghim MIC S dng cho mt l hng mi M rng gii hn pha long 1 X X 5 20 hoc 30 Lu

V d: chuyn gii hn ngng sang cc bc MIC m rng gii hn V d: Chuyn MIC m rng gii hn sang cc bc gii hn ngng X V d: Chuyn t mt thng sang thit b c t ng cc bc. Chuyn t tng sinh qua m sang th nghim MIC nhanh Thc hin cc nghin cu nh gi hiu lc t ch ti phng xt nghim. X Thc hin cc nghin cu nh gi hiu lc t ch ti phng xt nghim.

Gim gii hn pha long

S dng phng php mi (cng cng ty)

Thay i nh sn xut test MIC

M100-S21 Thay i nh sn xut mi trng canh thang hoc thch Chun b huyn dch vi khun S dng cc phng php chun b huyn dch vi khun/chun ha c bng cc phng php c hng dn kim sot cht lng X

V d: Chuyn vic iu chnh c bng mt thng sang phng php o quang c hng dn kim sot cht lng.

Chuyn vic chun b huyn dch vi khun/chun ha sang mt phng php ph thuc vo k thut ca ngi tin hnh.

V d: Chuyn vic iu chnh c bng mt thng sang mt phng php khc m khng dng o quang.

Thit b/phn mm (v d, my c ng knh vng c ch t ng) Cc phn mm cp nht nh hng n kt qu AST X Kim sot tt c cc thuc, khng ch nhng thuc lin quan trong vic iu chnh phn mm. Ph thuc vo vic sa cha (v d: cc b phn nh thit b o quang) c th cn tin hnh cc th nghim b sung (v d, nm ngy).

Sa cha thit b nh hng n kt qu AST

LU 1:

Khi c thm bt k khng sinh MI no, cn th nghim kim sot cht lng 20-30 ngy lin tc (xem M07-A8, Phn 16.7.2) trc khi s dng.

LU 2:

M100-S21 QC c th tin hnh trc hoc ng thi vi cc chng bnh phm. Kt qu ca bnh phm c th c bo co trong ngy nu kt qu kim tra cht lng nm trong gii hn cho php. Cn tun th cc hng dn v qui nh ca nh sn xut. Cc gii hn QC MIC cho php i vi th nghim nhy cm khng sinh c ph duyt bi FDA c th khng vi gii hn QC CLSI. Ngi s dng nn tun th hng dn ca tng phng php. i vi cc trng hp kt qu nm ngoi gii hn, tham kho M07-A8, Phn 16.9. Canh thang, nc v nc mui sinh l pha huyn dch vi khun khng cn kim tra cht lng thng qui. Lu

LU 3: LU 4: LU 5: LU 6:

a. Khng c b qua vic kim tra cht lng thng qui hng tun hoc hng ngy.

M100-S21 Bng 4G. Hng dn x l cc vn v kim sot cht lng MIC Bng ny cung cp cc hng dn v nguyn nhn v x l s c cc trng hp kim sot cht lng nm ngoi gii hn cho php ca cc th nghim nhy cm khng sinh s dng mi trng canh thang CAMHB vi pha long. Tham kho M07-A8, MIC, Phn 16, Hng dn kim sot cht lng v Quy trnh m bo cht lng,. Cc trng hp kt qu nm ngoi gii hn trc ht cn phi tin hnh lp li th nghim. Nu vn khng c gii quyt, hng dn x l s c cung cp mt s bin php b sung cho cc trng hp kt qu kim sot cht lng nm ngoi gii hn, Ngoi ra, nu vn khng gii quyt c vn , cn thng bo cho nh sn xut v cc vn ca sn phm. Lu chung (1) Duy tr chng QC: trnh cy chuyn nhiu ln. Cy chuyn chng QC mi t ng d tr (dng lu gi). Nu s dng chng ng kh, tun th hng dn ca nh sn xut. Gi chng gc E. coli ATCCa 35218 and K. pneumoniae ATCC 700603 -60 C hoc thp hn v chun b chng dng s dng hng tun. Khng sinh Aminoglycosides Chng kim tra cht lng Bt k Quan st MIC qu cao Nguyn nhn c th pH mi trng qu thp Lu /Khc phc Khong pH cho php = 7.27.4. Trnh C0 2 v to ra pH thp hn Khong pH cho php = 7.2-7.4 Gii hn cho php = Ca++ 20-25 mg/L Mg++ 10-12.5 mg/L Gii hn cho php = Ca++ 20-25 mg/L Mg++ 10-12.5 mg/L S dng l khoanh giy khng sinh mi. Kim tra iu kin bo qun v ton b bao gi.

Aminoglycosides Aminoglycosides

Bt k P. aeruginosa ATCC 27853 P. aeruginosa ATCC 27853 E. coil ATCC 35218

MIC qu thp MIC qu cao

pH mi trng qu cao Ca++ v/hoc Mg ++ qu cao Ca++ v/hoc Mg ++ qu thp Axit clavulanic b bin tnh. Khoanh giy mt hiu lc.

Aminoglycosides

MIC qu thp

Amoxicillinclavulanic axit

MIC qu cao

M100-S21 Nhm Beta-lactam Bt k MIC ban u c th chp nhn c nhng sau b tng v c th nm ngoi gii hn. Khoanh giy khng sinh b gim hiu lc S dng l khoanh giy mi. Kim tra iu kin bo qun v ton b bao gi. Imipenem, axit clavulanic, v cefaclor l cc khng sinh d b bin tnh.

Aztreonam Cefotaxime Cefpodoxime Ceftazidime Ceftriaxone Ceftriaxone Cefotaxime/clavulanic axit Ceftazidime/clavulanic axit Carbapenems

K. pneumoniae ATCC 700603

MIC qu thp

Mt plasmid m ha enzyme Xem lu chung (1) v duy tr beta-lactamase mt cch ngu chng kim tra cht lng QC. nhin

K. pneumoniae ATCC 700603

Th nghim khng nh Mt plasmid m ha enzyme Xem lu chung (1) v duy tr ESBL m tnh beta-lactamase mt cch ngu chng kim tra cht lng QC. nhin Nng Zn++ trong mi trng qu cao S dng l mi trng mi thay th.

P. aeruginosa ATCC MIC qu cao 27853

Carbapenems

P. aeruginosa ATCC MIC qu cao 27853

Cc khng sinh b gim tc dng

S dng l mi trng mi thay th. Kt qu imipenem lp li 4 g/mL vi P. aeruginosa ATCC 27853 c th phn nh s gim cht lng ca khng sinh.

M100-S21 Penicillins S. aureus ATCC 29213 MIC qu cao Cc chng QC c kh nng Lp li th nghim cn thn v sinh -lactamase; qu thi iu chnh thi gian gian c th dn n tng MICs

Penicillins

Bt k

MIC qu thp

pH mi trng qu thp

Khong pH cho php = 7.2-7.4. Trnh C02 v to ra pH thp hn. Khong pH cho php = 7.2-7.4

Penicillins

Bt k

MIC qu cao

pH mi trng qu cao

Carbenicillin

P. aeruginosa ATCC 27853

MIC qu cao

Cc chng QC tr nn khng thuc sau khi cy chuyn nhiu ln. Axit clavulanic b bin tnh. Khoanh giy mt hiu lc.

Xem lu (1) v duy tr chng kim tra cht lng QC.

Ticarcillin-clavulanic axit

E. coli ATCC 35218

MIC qu cao

S dng l khoanh giy mi. Kim tra iu kin bo qun v ton b bao gi. Khong pH cho php= 7.2-7.4. Trnh trong iu kin C0 2, thng to pH thp hn.

Clindamycin

S. aureus ATCC 25923 E. faecalis ATCC 29212

MIC qu cao

pH mi trng qu thp

M100-S21 Bng 4G. (Tip) Khng sinh Clindamycin Chng kim tra cht Quan st lng S. aureus MIC qu thp ATCC 29213 E. faecalis ATCC 29212 S. aureus ATCC 29213 E. faecalis ATCC 29212 S. aureus ATCC 29213 E. faecalis ATCC 29212 S. aureus ATCC 29213 E. faecalis ATCC 29212 Bt k MICs qu cao MICs qu thp Nguyn nhn c th pH mi trng qu cao Lu /Khc phc Gii hn pH cho php = 7.2-7.4

Daptomycin

Hm lng Ca++ qu thp Hm lng Ca++ qu thp

Macrolides v Ketolides

MIC qu cao

pH mi trng qu thp

Gii hn hm lng Ca++ cho php 50 g/mL trong CAMHB iu chnh nng Ca++ hoc s dng l mi trng mi thay th. Khong pH cho php= 7.2-7.4. Trnh trong iu kin C0 2, thng to pH thp hn. Khong pH cho php= 7.2-7.4.

Macrolides v Ketolides

MIC qu thp

pH mi trng qu cao

Quinolones

MIC qu cao

pH mi trng qu thp

Quinolones Tetracyclines Tetracyclines Tetracyclines

Bt k Bt k Bt k Bt k

MIC qu thp MIC qu thp MIC qu cao MIC qu cao

pH mi trng qu cao pH mi trng qu thp pH mi trng qu cao Hm lng Ca++ v/hoc Mg++ qu cao

Khong pH cho php= 7.2-7.4. Trnh trong iu kin C0 2, thng to pH thp hn. Gii hn pH = 7.2-7.4 Gii hn pH = 7.2-7.4 Gii hn pH = 7.2-7.4 Gii hn cho php = Ca++ 2025 mg/L Mg++10-12.5 mg/L

M100-S21 Tetracyclines Bt k MIC qu thp Hm lng Ca v/hoc Mg++ qu thp

++

Gii hn cho php = Ca++ 2025 mg/L Mg++10-12.5 mg/L

Tigecycline

Bt k

MIC qu cao

CAMHB khng c chun b mi

Bc pha long vi chng chun phi c s dng hoc lu gi nhit ng trong vng 12 khi CAMHB c chun b

Nhiu loi

Bt k

Nhiu gi tr MICs qu thp

Huyn dch vi khun qu trong (long); li trong qu trnh chun b huyn dch vi khun

Lp li s dng thit b o c chun McFarland 0.5 hoc thit b chun ha c. Kim tra hn dng v iu kin bo qun nu dng ng barium sulfate hoc latex. Kim tra cc bc trong chun b huyn dch v qui trnh pha huyn dch. Thc hin phng php cy m khun lc trc khi v sau khi (E. coli ATCC 25922 gn xp x 5 x 105 CFU/mL). S dng l mi trng thay th

Nhiu loi

Bt k

Nhiu gi tr MICs qu cao hoc qu thp

CAMHB khng ti u

M100-S21 Nhiu loi Bt k Nhiu gi tr MICs qu cao hoc qu thp Huyn dch vi khun qu c Lp li s dng thit b o c chun McFarland 0.5 hoc thit b chun ha c. Kim tra hn dng v iu kin bo qun nu dng ng barium sulfate hoc latex. Kim tra cc bc trong chun b huyn dch v qui trnh pha huyn dch. Thc hin phng php cy m khun lc trc khi v sau khi (E. coli ATCC 25922 gn xp x 5 x 105 CFU/mL). Ngoi nhim. Lp li th Huyn dch vi khun khng nghim QC. S m bo hoc pha trn huyn dng l mi dch khng ph hp. Nng trng mi thay thuc trong cc ging khng th. chnh xc. Th tch mi trng trong cc ging khng chnh xc. C th do li c kt qu/li sao chp Kim tra bc c kt qu S dng l thay th

Nhiu loi

Bt k

Nhiu ging b b qua

Nhiu loi

Bt k

Mt s im MIC qu cao hoc qu thp

M100-S21 Bng 4G. (Tip) Khng sinh Nhiu loi Chng kim tra cht lng S. pneumoniae ATCC 49619 Quan st Nhiu gi tr MICs qu thp Nguyn nhn c th Huyn dch vi khun c chun b t a cy chuyn qu c. Ch nn s dng a trong vng 18-24h. MHB v LHB khng ti u. C th chng QC ny tt hn chng khc trong vic kim tra cht lng (v d, P. aeruginosa ATCC 27853 tt hn E. coli ATCC 25922 i vi imipenem. Bn lun/Hnh ng Cy chuyn chng QC v lp li th nghim QC; hoc cy chng mi QC t ng d tr. S dng l mi thay th.

Nhiu loi

Bt k

Mt chng QC nm ngoi gii hn, nhng cc chng khc nm trong gii hn i vi cng mt loi khng sinh.

Xc nh xem chng QC nm trong gii hn c thch hp lm ch s vi khng sinh th nghim hay khng. Lp li th nghim vi chng ny khng nh li kt qu. nh gi cc chng thay th vi cc gi tr MIC bit. Thc hin vic x l s c bt u t vn cp chng QC/khng sinh.

Nhiu loi

Bt k

Hai chng QC nm ngoi gii hn i vi cng mt loi khng sinh.

Phn nh vn v Thc hin vic x l s c bt khng sinh. u. C th y l mt li h thng

M100-S21 Nhiu loi Bt k Mt kt qu QC nm ngoi gii hn, nhng khng sinh khng c bo co s dng trn bnh nhn (v d, khng c trong liu php iu tr c s dng trong bnh vin) Nu khng sinh thng khng c bo co, khng cn th nghim lp li m c th s dng cc kim sot ph hp khc thay th khng sinh c kt qu nm ngoi gii hn ny

Vit tt: CAMHB, Canh thang Mueller-Hinton iu chnh cation; CFU, n v khun lc; ESBL, Khng betalactamase ph rng; LHB, mu cu ly gii; MHB, canh thang Mueller-Hinton; MIC, Nng c ch ti thiu: QC, qun l cht lng

M100-S21 Bng 5A. Dung mi v cht ha tan chun b dung dch khng sinh Khng sinh Amikacin Amoxicillin Amoxicillin-clavulanic acid Ampicillin Azithramycin Azlocillin Aztreonam Besitloxacin Carbenicillin Cefaclor Cefadroxil Cefamandole Cefazolin Cefdinir Cefditoren Ceepime Cefetamet Cefixime Cefmetazole Cefonicid Cefoperazone Cefotaxime Cefotetan Ceoxitin Cepodoxime Cefprozil Ceftaroline Dung mi ha tan Nc m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 8.0, 0.1 mol/L 95% ethanol hoc axit acetic bnge,f Nc Saturated solution sodium bicarbonate Methanol Nc Nc m Phosphate, pH 6.0, 0.1 mol/L Nc m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 7.0, 0.1 mol/L Nc Nc Nc Nc DMSO e Nc 0.10% (11.9 mmol/L) dung dch Natri bicarbonate Nc DMSO chim 30% th tch tng, sau xc nh th tch vi mui Cht ha tan m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L Mi trng canh thang Nc Nc Nc m Phosphate, pH 6.0, 0.1 mol/L Nc Nc m Phosphate, pH 6.0, 0.1 mol/L VVater m Phosphate, pH 7.0, 0.1 mol/L

Nc Nc 0.85% nc mui sinh l

Ceftazidime Ceftibuten Ceftizoxime Ceftobiprale Ceftraxone Cefuroxime Cephalexin

Natri carbonated 1/10 voi DMSO Nc DMSO thm axit acetic bng e,h Nc m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L

Nc Nc Nc, vortex mnh m Phosphate, pH 6.0, 0.1 mol/L Nc

M100-S21 Cephalothin Cephapirin Cephradine Chloramphenicol Cinoxacin Ciprofloxacin Clarithromycin Clavulanic axit Clinatloxacin Clindamycin Colistina Dalbavancin Daptomycin m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L 95% ethanol 1/2 th tch nc, thm 1 mol/L NaOH, nh git ha tan Nc Methanole or glacial acetic axite,f m Phosphate, pH 6.0, 0.1 mol/L Nc Nc Nc DMSO Nc Nc Nc Nc Nc Nc m Phosphate, pH 6.5, 0.1 mol/L m Phosphate, pH 6.0, 0.1 mol/L Nc DMSOg, Nc

M100-S21 Bng 5A. (Tip) Khng sinh Dirithromycin Doripenem Doxycycline Enoxacin Ertapenem Erythromycin Faropenem Fidaxomicin Fleroxacin Garenoxacin Gatitloxacin Gemiloxacin Gentamicin lclaprim Imipenem Kanamycin Levofloxacin Linezolid Linopristin-tlopristin Lomefloxacin Loracarbet Mecillinam Meropenem Methicillin Metronidazole Mezlocillin Minocycline Moxalactam (diammonium salt) Moxiloxacin Mupirocin Nafcillin
b

Dung mi ha tan Axit acetic bngf 0.85% nc mui sinh l Nc 1/2 th tch nc, nh git 0.1 mol/L NaOH ha tan m phosphate, pH 7.2, 0.01 mol/L 95% ethanol hoc axit acetic bnge,f Nc DMSO 1/2 th tch nc, nh git 0.1 mol/L NaOH ha tan Nc (kt hp khuy) Nc (kt hp khuy) Nc Nc DMSOg m Phosphate, pH 7.2, 0.01 mol/L Nc 1/2 th tch nc, nh git 0.1 mol/L NaOH ha tan Nc DMFk Nc Nc Nc Nc Nc DMSOe Nc Nc 0.04 mol/L HOI ( yn 1.5 n 2 h)

Cht ha tan Nc 0.85% nc mui sinh l Nc m phosphate, pH 7.2, 0.01 mol/L Nc Nc Nc Nc

Nc m Phosphate, pH 7.2, 0.01 mol/L Nc Nc

Nc m Phosphate, pH 6.0, 0.1 mol/L

Nc Nc Nc

Nc

M100-S21 Nalidixic axit Netilmicin Nitazoxanide Nitrofurantoinc Norfloxacin Ofloxacin Oritavancin Oxacillin Penicillin Piperacillin Polymyxin B Quinupristin-dalfopristin Ramoplanin Razupenem Rifampin Rifaximin Sparfloxacin Spectinomycin Streptomycin Bng 5A. (Tip) Khng sinh Sulbactam Sultonamides Sulopenemj Tazobactam Teicoplanin Telavancin Telithromycin Tetracycline Ticarcillin Dung mi ha tan Nc 1/2 th tch nc nng v mt lng ti thiu 2.5 mol/L NaOH ha tan 0.01 M m phosphate, pH 7.2, vortex ha tan Nc Nc DMSOg Axit acetic bngf Nc m Phosphate , pH 6.0, 0.1 mol/L Cht ha tan Nc 0.01 M m phosphate, pH 7.2 Nc Nc Nc m Phosphate, pH 6.0, 0.1 mol/L 1/2 th tch nc, nh git 0.1 mol/L NaOH ha tan dissolve Nc DMSOc,l m Phosphate, pH 8.0, 0.1 mol/L 1/2 th tch nc 1/2 th tch nc 0.002% polysorbate-80 in wate Nc Nc Nc Nc Nc Nc m Phosphate, pH 7.2, 0.01 mol/L Methanole (nng ti a = 640 g/mL) Methonol Nc Nc Nc
i

DMSOc,l m Phosphate, pH 8.0, 0.1 mol/L Nc Nc 0.002% polysorbate-80 trong nci

Nc Nc m Phosphate, pH 7.2, 0.01 mol/L Nc (kt hp khuy) 0,1 M m phosphate, pH 7,4 +0,45% Natri dodecyl sulfonate

M100-S21 Ticarcillin-clavulanic acid Tigecycline Tinidazole Tizoxanide Tobramycin Trimethoprim Trimethoprim (nu lactate) Trospectomycin Ulifloxacin (prulitloxacin) Vancomycin Nc m phosphate, pH 6.0, 0.1 mol/L Nc DMSOe, l DMSOe, l Nc 0.05 mol/L lacticehoc axit hydrochlorice, 10% th tch cui Nc Nc DMSOg m Phosphate, pH 6.0, 0.1 mol/L Nc Nc DMSOe, l Nc (c th cn un nng)

Nc

LU : Thng tin in m l mi hoc c iu chnh so vi phin bn trc Ghi ch a. Colistin s dng trong th nghim tnh nhy cm khng sinh l colistin sulfate, khng phi colistin methane sulfonate (sulfomethate). b. Mui diammonium ca maxalactam rt n nh, nhng gn nh ton b l dng ng phn R tinh khit. Moxalactam s dng trn lm sng l hn hp ca hai dng ng phn R v S vi t l 1:1. Do , mui c ha tan trong 0,04 mol/l HCl v trong 1,5 n 2h chuyn hon ton b dng ng phn S sang dng ng phn R. c. Phng php thay th, nitrofurantoin c th ha tan trong dimethyl sulfoxide (DMSO). d. Natri carbonate (Na2CO3) khan c dng vi lng chnh xc l 10% ceftazidime. Natri carbonate c ha tan trong nc. Khng sinh c ha tan trong dung dch natri carbonate, b sung nc t th tch va . Dung dch ny c s dng cng sm cng tt, c th bo qun ti a 6h nhit khng qu 25 oC. e. Cc hp cht ny c th c c tnh. Cn tun th cc hng dn an ton ca nh sn xut trc khi s dng cc vt liu ny. f. i vi axit acetic bng, s dng th tch nc, sau nh git axit acetic bng cho n khi ha tan hon ton, khng vt qu 2.5 L/mL. g. Dung dch ban u ca dalbavancin nn bt u t nng khng qu 1600 g/mL. Nng trung gian 100x nn pha long bng DMSO. T l pha long cui cng 1:100 nn pha trc tip vo mi trng CAMHB c b sung 0.002% (v/v) polysorbate-80, do nng cui cng ca DMSO trong mi tup s khng ln hn 1%. Xem Bng 7A. h. i vi mi ceftobiprole 1,5 mg, thm 110 L hn hp 10:1 MDSO v axit acetic bng. Vortex mnh trong 1 pht, sau vortex lin tc trong vng 15 pht. Thm nc ct va 1.0ml. i. Dung dch ban u ca oritavancin nn bt u t nng khng qu 1600 g/mL trong 0,002% polysorbate-80 trong nc. Nng trung gian 100x oritavancin nn c chun b trong 0,002 polysorbate-80 trong nc. T l pha long cui cng 1:100 nn pha trc tip vo mi trng CAMHB c b sung 0,002% polysorbate-80 (v/v), do nng cui cng ca polysorbate-80 trong mi tup s l 0,002%.

M100-S21 j. Cn pha MI mi ngy s dng. k. Dimethylformamide (DMF) t 25% th tch cui/nc l. Nng cui cng ca DMSO khng c php vt qu 1%. N c th c chun b theo quy trnh sau: 1) chun b dung dch d trc nng cao hn nng d tr d nh 10 ln (v d, chun b nng 12.800 g/mL hn l 1280 g/mL); 2) thm 1,8 mL nc kh trng vo mi ging thch; 3) thm 0,2 mL khng sinh pha long vo mi ging thch.

M100-S21 Bng 5B. Chun b dung dch m ca cc khng sinh vi hot tnh c biu hin theo n v

Khng sinh Potassium Penicillin G

Tinh cht (tham kho) 0,625 g/n v

(1)

Tnh ton cho g/mg

V d

Nhn hot tnh c biu hin theo n n v hot tnh/mg x 0.625 g/n v = Hot tnh v/mg vi 0.625 g/n v. g/mg (v d, 1592 n v/mg x 0,625 g/n v = 995 g/mg)

Sodium Penicillin G Polymyxin B

0,6 g/n v(1)

Nhn hot tnh c biu hin theo n n v hot tnh /mg x 0.6 g/n v = Hot tnh v/mg vi 0.6 g/n v. g/mg

10 000 n v/mg = 10 n v/g = 0.1 g/n v

(2)

Nhn hot tnh c biu hin theo n (v d, 1477 tnh /mg x x 0,6 g/n v = 886.2 n v hot n v/mg 0.1 g/n v = Hot tnh v/mg vi 0.1 g/n v. g/mg

Chia hot tnh c biu hin theo n (v d, 8120 tnh /mg / 100,1 g/n = Hot tnh n v hot n v/mg x n v/g v = 812 g/mg) v/mg vi 10 n v/g g/mg

Colistin sulfatea

30000 n v/mg = 30 n v/g = 0.03333 g/n v

(2)

Nhn hot tnh c biu hin theo n (v d, 8120 tnh /mg x / 10 n g/n v = Hot n v hot n v/mg 0.03333 v/mg vi 0.03333 g/n v. tnh g/mg (v d, 20277 n v/mg x 0,03333 g/n v = 676 Chia hot tnh c biu hin theo n n v hot tnh /mg / 30 n v/g = Hot tnh v/mg vi 30 n v/g g/mg (v d, 20277 n v/mg / 30 n v/g = 676 g/mg)

Streptomycin

785 n v/mg

(3)

M100-S21 Chia s n v c a ra cho 785. S ([S n v hiu lc/mg] / [785 n v/mg]) x (850 thu c % bt tinh khit. Nhn % ny M9/m9) = Hiu lc g/mg [v d, (751 n v/mg / 785 vi 850, l lng streptomycin tinh n v/mg) x 850 g/mg = 813 g/mg] sch nht. Con s ny s tng ng Nu bt cha 2,8% nc: vi hot tnh trong g/mg 813 x (1-0.028) = hiu lc 813 x 0.972 = 790 g/mg

Ghi ch Khng s dng colistin methanesulfonate i vi th nghim nhy cm khng sinh in vitro.

Ti liu tham kho i vi Bng 5A: 1. Kucers A, Crowe SM, Grayson ML, Hoy JF. Penicillin G. The Use of Antibiotics. 5th ed. Oxford, UK: Butterworth-Heinemann; 1997:3-70. 2. Kucers A, Crowe SM, Grayson ML, Hoy JF. Polymyxins. The Use of Antibiotics. 5th ed. Oxford, UK: Butterworth-Heinemann; 1997:667-675. 3. United States Department of Agriculture, OPHS, Laboratory QA/QC Division. Bioassay for the detection, identification and quantitation of antimicrobial residues in meat and poultry tissue. 2004;1-58, vol. MLG 34.01.

M100-S21 Bng 5C. Chun b dung dch v mi trng i vi cc khng sinh phi hp

Khng sinh Amoxicillin-axit clavulanic axit

T l phi hp T l 2:1

Pha ch Pha ch nng ban u

V d vi nng ban u 128/64 mt ng, chun b ng d tr c nng 10x ca amoxicillin 2560 g/mL v 1280 g/mL i vi clavulanic axit. Sau phi hp mt lng tng ng vi mi ng pha long ban u, m sau s t c mt phi hp c nng 1280/640 g/mL. Pha long 1:10 vi canh thang t c nng cui cng mong mun trong mi ging.

(amoxicillin:clavulanic axit). 10x) vi t l 2:1 ratio v pha long cc mc nng cn

Ampicillinsuibactam Piperacillintazobactam

T l 2:1 (ampicillin:sulbactam). Nng c nh ca tazobactam 4g/mL.

Ging vi amoxicillinclavulanic axit. Chun b nng ban u 10x ca piperacillin mc gp i nng cn v pha long gim dn 2 ln theo th t. Thm mt th tch tng ng tazobactam 80 g/mL vo mi tup. i vi nng ban u 128/4, chun b nng ng d tr ca piperacillin 2560 g/mL v pha long gim dn 2 ln theo th t t c nng cui cng trong danh sch. Pha dung dch ng d tr tazobactam 80 g/mL. Thm th tch tng ng tazobactam 80 g/mL vo mi tup piperacillin pha long. V d, 5 mL dung dch 2560 g/mL piperacillin + 5 mL of 80 g/mL tazobactam = 10 mL of 1280/40 g/mL piperacillin-tazobactam. Pha long 1:10 vi canh thang thu c nng cui cng trong mi tup.

Ticarcillin-clavulanic axit

Nng c nh clavulanic axit t 2 g/mL.

Chun b nng ban u 10x ca ticarcillin mc cao gp i nng cn v pha long gim dn 2 ln theo th t. Thm mt lng th tch tng ng clavulanic axit 40 g/mL vo mi tup pha long.

M100-S21 i vi nng ban u 128/4, chun b dung dch ng d tr 10x ca ticarcillin 2560 g/mL v pha long gim dn 2 ln theo th t t nng thp nht cui cng mong mun. Pha dung dch ng d tr clavulanic axit 40 g/mL. Sau thm mt th tch tng ng clavulanic axit 40 g/mL vo mi tup ticarcillin pha long. V d, 5 mL dung dch ticarcillin 2560 g/mL + 5 mL clavulanic axit 40 g/mL = 10 mL ticarcillin-clavulanic axit 1280/20 g/mL. Pha long 1:10 trong canh thang t nng cui cng mong mun.

M100-S21 Bng 5C. (Tip) Khng sinh Trimethoprimsulfamethoxazole T l phi hp T l 1:19 (trimethoprim: sulfamethoxazole) Pha ch Chun b nng ban u 10x ca trimethoprim 1600 g/mL (hoc 1280 g/mL sau s pha long t nng 160 g/mL). Chun b nng ban u 10x ca V d i vi nng ban u 8/152, chun b nng 10x ca trimethoprim 160 g/mL. Chun b nng ban u 10x ca sulfamethoxazole 3040 g/mL. Thm mt th tch tng ng trimethoprim 160 g/mL v sulfamethoxazole 40 g/mL vo tup pha long ban u v sau pha long gim dn 2 ln theo th t. V d, 5

sulfamethoxazole a log2 ca mL trimethoprim 160 g/mL v 5 mL sulfamethoxazole 1520 g/mL (v d, 1520, 3040 g/mL = 10 mL trimethoprim-sulfamethoxazole

3040, hoc 6080 g/mL) ph 80/1520. Pha long 1:10 vi canh thang t nng thuc vo nng ban u mong mun. Quinupristindaltopristin LinopristinAopristin LU : pha nng trung gian ca cc khng sinh, s dng cng thc C1 x V1 = C2 x V2, trong , C1 l nng ca dung dch m (thng l 1280 g/mL hoc ln hn); V1 l th tch cn tnh to nng trung gian; C2 l nng trung gian mong mun; v g/mL V2 l th tch dung dch trung gian cn pha. Khng cn pha ch v bt khng sinh dng phi hp cui cng mong mun.

V d: pha 20ml dung dch 40 g/mL t dung dch m 1280 g/mL

M100-S21 C1 x V1 = C2 x V2 1280 g/mL x V1 = 40 g/mL x 20 mL V1 = 40 g/mL 20 mL 1280 g/mL

V1 = 0.625 mL

Do , thm 0,625 ml dung dch m 1280 g/mL vo 19,375 ml dung mi pha long (thng l nc) thu c 20ml dung dch 40 g/mL.

M100-S21 Bng 6A. H thng cc dung dch khng sinh s dng trong th nghim tnh nhy cm bng phng php pha long trn thch Dung dch khng sinh Bc Nng (g/mL) Ngun Th tch (mL) Pha long (mL) Nng trung gian (g/mL) Nng cui cng 1:10 pha long trn thch (g/mL) 5120 1 2 3 4 5 6 7 8 9 10 11 12 5120 5120 5120 640 640 640 80 80 80 10 10 10 ng d tr ng d tr ng d tr ng d tr Bc 3 Bc 3 Bc 3 Bc 6 Bc 6 Bc 6 Bc 9 Bc 9 Bc 9 2 1 1 2 1 1 2 1 1 2 1 1 2 3 7 2 3 7 2 3 7 2 3 7 5120 2560 1280 640 320 160 80 40 20 10 5 2.5 1.25 512 256 128 64 32 16 8 4 2 1 0.5 0.25 0.125 9 8 7 6 5 4 3 2 1 0 -1 -2 -3 Log2

LU : Bng ny c Ericsson HM, Sherris JC iu chnh. Th nghim nhy cm khng sinh. Bo co nghin cu hp tc quc t. Acta Pathol Microbiol Scand. 1971; 217 (suppl B):1-98.

M100-S21 Bng 7A. H thng cc dung dch khng sinh s dng trong th nghim tnh nhy cm bng phng php pha long trn canh thang Dung dch khng sinh Bc Nng (g/mL) 1 2 3 4 5 6 7 8 9 10 11 12 13 5120 512 512 512 64 64 64 8 8 8 1 1 1 ng d tr Bc 1 Bc 1 Bc 1 Bc 4 Bc 4 Bc 4 Bc 7 Bc 7 Bc 7 Bc 10 Bc 10 Bc 10 1 1 1 1 1 1 1 2 1 1 1 1 1 Ngun Th tcha (mL) + 9 1 3 7 1 3 7 2 3 7 1 3 7 CAMHBb Th tch (mL)
a

Nng cui cng = 512 256 128 64 32 16 8 4 2 1 0.5 0.25 0.125 (g/mL) 9 8 7 6 5 4 3 2 1 0 -1 -2 -3

Log 2

LU : Bng ny c Ericsson HM, Sherris JC iu chnh. Th nghim nhy cm khng sinh. Bo co nghin cu hp tc quc t. Acta Pathol Microbiol Scand. 1971; 217 (suppl B):1-90. Ghi ch a. Cc th tch bt k c th tnh ton da trn bng ny, ph thuc vo s lng xt nghim cn tin hnh. b. iu chnh cation, nu cn thit, thc hin trc bc ny.

M100-S21 Bng 7B. Chun b dung dch cc khng sinh khng tan trong nc s dng trong th nghim tnh nhy cm bng phng php pha long trn canh thang Dung dch khng sinh Cht ha tan (mL) Nng Bc 1 2 3 4 5 6 7 8 9 10 11 12 13 14
*

Nng trung gian (g/mL) Nng cui cng 1:100 = 1600 = 16 8.0 4.0 2.0 1.0 0.5 0.25 0.125 0.0625 0.03 0.016 0.008 0.004 0.002 (g/mL) 4 3 2 1 0 -1 -2 -3 -4 -5 -6 -7 -8 -9 Log2

Th tch Ngun ng d tr ng d tr ng d tr ng d tr Bc 4 Bc 4 Bc 4 Bc 7 Bc 7 Bc 7 Bc 10 Bc 10 Bc 10 Bc 13 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 1.5 3.5 0.5 1.5 3.5 0.5 1.5 3.5 0.5 1.5 3.5 0.5 (mL)

(v d, DMSO )
*

(g/mL) 1600 1600 1600 1600 200 200 200 25 25 25 3.1 3.1 3.1 0.4

800 400 200 320 160 80 40 20 10 5 2.5 1.25 0.2

Dimethyl sulfoxide

M100-S21 Ph lc A. Nhng ngh cho th nghim xc nhn vi cc kt qu nh danh v khng sinh cho kt qu l Khng (R), Trung gian (I) v khng nhy cm (NS) Mc ph bin v ngha ca kt qu khng v nhng bc lm xc nh kt qua Nhm I Nhm II Nhm III C th ph bin, Khng c bo co Khng ph bin mi nhng thng c hoc gn nh cha bao trung tm nghin cu cho l nhng vn v gi c bo co (labo) mt dch t hc Cc bc tin hnh: Xc nhn li m Xc nhn li m Xc nhn li m (bnh nhn hoc (bnh nhn hoc (bnh nhn hoc bnh phm) v bnh phm) v bnh phm) v khng sinh (xem khng sinh (xem khng sinh (xem ch thch a). ch thch a) nu kt ch thch a) nu kt qu ny khng ph qu khng ph bin Bo co ti khoa Vi khun hoc nhm vi c im kiu hnh khng c bin trung tm ca trung tm ca bn. a chng nhim khun. khun pht hin bn. Vic xc nhn li tin Gi ti phng xt hnh cng khoa nghim ca cc trung Vic xc nhn li tin hnh cng khoa chng nhim nu nh tm Y t Cng cng. chng nhim nu nh quy trnh bo co c Lu gi chng. quy trnh bo co bit hoc cc bc Chu : c l s ph hp c bit hoc cc lm k cng hn nu cnh bo ti khoa bc lm k cng c t ra. chng nhim khun hn c t ra. trc sau thc hin Cng vi trung tm th nghim xc nhn dch t hc trong vng tin hnh xc inh chng no s c bo co vo thi im bo co. Bt k Enterobacteriaceae Carbapenem I hoc Rb X Amikacin, gentamicin, v X tobramycin - R Escherichia coli Cephalosporin ph rng I hoc Rb X

M100-S21 Klebsiella spp. Proteus mirabilis Salmonella spp.d

Cephalosporin th h III v/hoc fluoroquinolone R

M100-S21 Ph lc A. (Tip) Acinetobacter baumannii Pseudomonas aeruginosa Colistin/polymycin R Carbapenem I hoc R Colistin/polymycin I hoc R Amikacin, gentamicin, v tobramycin R Carbapenem I hoc R Trimethoprim-sulfamethoxazole I hoc R Carbapenem NS Cephalosporin ph rngc NS Fluoroquinolone NS Amoxicillin-clavulanic acid R Ampicillin R v -lactamase m tnh Cephalosporin ph rngc NS FluoroquinoloneI hoc R Ampicillin hoc penicillin R Cephalosporin ph rngc NS Meropenem NS Minocycline NS Ampicillin hoc penicillin I Azithromycin NS Rifampin I hoc R Chloramphenicol I hoc R Fluoroquinolone I hoc R Daptomycin NS Linezolid R Vancomycin R Aminoglycoside nng cao R Vancomycin MIC 8 g/mLe Daptomycin NS Linezolid R Quinupristin-dalfopristin I hoc R Vancomycin MIC = 4 g/mL Oxacillin R X X X X X X

Stenotrophomonas maltophilia Haemophilus influenza

X X X X

Neisseria gonorrhoeae Neisseria meningitides

X X X X X

Enterococcus spp.

Staphylococcus aureus

M100-S21 Ph lc A. (Tip) Staphylococcus coagulase m tnh Daptomycin NS X Linezolid R Quinupristin-dalfopristin I or R Vancomycin I hoc Rf Streptococcus pneumonia Linezolid NS X Vancomycin NS Fluoroquinolone I or R X Imipenem or meropenem I or R Quinupristin-dalfopristin I or R Rifampin I or R Using nonmeningitis breakpoints: X Amoxicillin or penicillin R Cephalosporin ph rngc R Streptococcus, tan mu g Ampicillin or penicillin NS X Cephalosporin ph rngc NS Daptomycin NS Ertapenem hoc meropenem NS Linezolid NS Vancomycin NS Quinupristin-dalfopristin I hoc R X Streptococcus, nhm viridans Daptomycin NS X Ertapenem or meropenem NS Linezolid NS Quinupristin-dalfopristin I hoc R Vancomycin NS Vit tt: I, Khng trung gian; MIC, Nng c ch ti thiu; NS, Khng nhy cm; R, Khng; CoNS, Staphylococcus coagulase m tnh. Khng nhy cm: L mt cch din gii kt qu dng cho mt s chng vi khun ch c tiu chun c kt l nhy cm. Bi v him hoc khng c cc trng hp khng xy ra cc chng vi khun ny. Cc chng vi khun c gi tr MIC cao hn hoc c ng knh vng c ch thp hn gi tr nhy cm cn c bo co l khng nhy cm. LU 1: Mt chng cho kt qu khng nhy cm khng c ngha l chng thc s c c ch khng. iu ny c th do cc chng, c gi tr MIC ln hn gi tr nhy cm, thiu c ch khng. C ch khng ny c th gp phi trong nhm phn b t nhin rng sau thi im xy dng gi tr nhy cm.

M100-S21 LU 2: i vi cc chng cho kt qu khng nhy cm, phn lp nh danh v th nghim nhy cm khng sinh cn c khng nh li (Xem ch thch a). a. m bo rng kt qu ca th nghim khng sinh v nh danh vi khun l chnh xc v d lng gi. Cn nhc cc bc sau: 1. Kim tra li nhng trong qu trnh gh chp s sch, nhim bn, bc thang pha long b thiu ging, a nui cy, card. 2. Kim tra nhng bo cao trc trn cng mt bnh nhn xc nh chng vi khun tng c phn lp v xc nh sm. 3. Thc hin li ton b qu trnh nh dang v khng sinh bng phng php ban u m bo th nghim cho kt qu c tnh lp li. (Vi nhm I v II, chn lc mt s chng b qua bc 3 tin hnh lun bc 4 v 5. Vi nhm III, lm li th nghim hoc/v cc th nghim xc nh c l khng cn thit nu kt qu khng c xc nh bi trung tm ca bn.) 4. Xc nhn li qu trnh nh danh c thc hin bng mt phng php khc trong cng mt labo hoc c tin hnh ti labo tham chiu. 5. Xc nhn li kt qu khng sinh bng mt phng php khc (v d cng mt labo hoc ti labo tham chiu). Phng php th hai c l l phng php chun thc ca CLSI (v d: vi pha long canh thang, pha long trn thch, hoc khoanh giy khuch tn) hoc mt phng php c thng mi ha c ph chun bi FDA. b. MIC ca Imipebem cho cc chng Proteus spp., Providencia spp., v Morganella morganii cho xu hng cao hn (v d, MIC trong khong gi tr Khng trung gian v Khng mi) so vi MIC ca doripenem. Nhng chng ny c MIC cao hn bi nhng c ch khc ngoi c ch to ra carbapenemase. c. Cephalosporin ph rng = cephalosporin th h III v IV (xem ph lc III). d. trnh ln cc trung tm dch t chc nng kt qu khng sinh cho Salmonella spp. m khng trung gian hoc khng vi cephalosporin th h III v/hoc khng trung gian hoc khng fluoroquinolone hoc khng vi nalidixic acid. e. Rt him khi gp. Ch c gi tr chng nhim khun v dch t, tin hnh theo cc khuyn co ca nhm I nhc nh khoa chng nhim khun v cc c quan c chc nng dch t. f. C mt vi chng Staphylococcus coagulase m tnh (CoNS) khi tin hnh th nghim MIC ca vancomycin ri vo khong gi tr khng trung gian. Tri ngc li, c rt t CoNS khng vancomycin.

M100-S21 g. Xc nhn li rng nhm C v G l nhm c khun lc ln khng phi l khun lc nh khng in hnh. Nhm C v G c khun lc nh khng in hnh bao gm nhm viridians.

M100-S21 Ph lc B. Khng ni ti-Enterobacteriaceae Khng ni ti c nh ngha l khng khng sinh mang tnh cht vn c hoc bm sinh (khng phi thu nhn c). c im ny phn nh dng khng khng sinh t nhin ca phn ln hoc gn nh ton b cc vi khun. Khng ni ti l ph bin, lm cho th nghim khng sinh tr ln khng cn thit. V d nh cc loi Citrobacter khng ni ti vi ampicillin. Bng sau c th hu dng bi 3 l sau: 1) cung cp mt phng php nh gi tnh chnh xc ca cc phng php th nghim; 2) h tr cho vic nhn dng cc c im kiu hnh ph bin; v 3) ph hp vi vic nh gi cc thng tin khng sinh tch ly. Trong bng, ch R xut hin tng cp vi khun / khng sinh c ngha l chng th nghim phi khng. Mt t l phn trm nh (1-3%) c th biu hin nhy do phng php khng chun, t bin hoc mc khng c biu hin mc thp. Kt qu khng sinh cho l nhy phi c xem li vi s thn trng. m bo rng kt qu khng sinh v nh danh chnh xc v tin cy. Xem Ph lc A, ch a. Cephamycins: Cefoxitin, Cefotetan Cephalosporin II: Cefuroxime Cephalosporin I: Cefazolin, Cephalothin Nitrofurantoin Tetracyclines Polymyxin B Colistin Amoxicillinclavulanate Piperacillin Ampicillinsulbactam Ampicillin Ticarcillin

Citrobacter freundii Citrobacter koseri Enterobacter aerogenes Enterobacter cloacae Escherichia coli Escherichia hermannii Hafnia alvei Klebsiella pneumoniae Morganella morganii Proteus mirabilis Proteus penneri Proteus vulgaris Providencia rettgeri Providencia stuartii Salmonella v Shigella spp. Serratia marcescens

R R R R R R R R R R R R R R R R R R R R R R R Khng c khng -lactam ni ti nhng chng ny R R R R R R R R R R R R R R R R R R R Khng c khng -lactam ni ti nhng chng ny R R R R R R R R R R R R R R R R R R R R R R R R Khng c khng -lactams ni ti nhng chng ny: xem Bng 2 A,ch (6) cho bo co R R R R R R R R

M100-S21 Yersinia enterocolitica R R R R Cephalosporin th h III, cefepime, aztreonam, ticarcillin-clavulanate, piperacillin-tazobactam, v carbapenems khng c trong danh sch, v khng c khng ni ti vi Enterobacteriaceae.

M100-S21 Ph lc C. Cc chng kim sot cht lng i vi cc th nghim tnh nhy cm khng sinh Chng QC c im chng Khoanh giy khuch tn E. faecalis ATCC 29212

MIC

Xt nghim sng lc

Khc

Vi khun gramdng d mc

Thch Vancomycin HLAR

nh gi mi trng ph hp i vi xt nghim MIC cho sulfonamide hoc trimethoprimd nh gi s ph hp ca nng cation trong mi l mi trng canh thang pha Mueller-Hinton i vi daptomycin

M100-S21 E. taecalis ATCC 51299

Khng vi vancomycin (VanB) v aminoglycosides mc cao

Thch Vancomycin HLAR

E. coli ATCC 25922

-Lactamase m tnh

Vi khun gramm d mc Neisseria meningitidis

Vi khun gram-m d mc Neisseria meningitidis Cc khng sinh s dng cho vi khun dng trong khng b sinh hc

E. coli ATCC 35218

Cha plasmid m ha TEM-1 lactamase (khngESBL)

a, b, e,f

Phi hp lactam/cht c ch -lactamase

Phi hp lactam/cht c ch -lactamase

H. influenzae ATCC 49247

BLNAR (betalactamase m tnh, khng ampicillin)

Haemophilus spp. Haemophilus spp.

M100-S21 H. influenzae ATCC 49766 Nhy cm vi Ampicillin Haemophilus spp. (c th d lng gi hn i vi mt s khng sinh lactams chn lc) H. pylori ATCC 43504 K. pneumoniae ATCC 700603 Cha SHV-18 ESBLb,e,f Sng lc ESBL v xt nghim khng nh N. gonorrhoeae ATCC 49226 CMRNG (N. gonorrhoeae khng penicillin qua trung gian chromosom N. gonorrhoeae Sng lc ESBL v xt nghim khng nh N. gonorrhoeae

Haemophilus spp. (c th d lng gi hn i vi mt s khng sinh lactams chn lc)

H. pylori

M100-S21 P. aeruginosa ATCC 27853 c Cha -lactamase AmpC do kch thch Vi khun gram m d mc Vi khun gramm d mc Cc khng sinh s dng cho vi khun dng trong khng b sinh hc nh gi hm lng cation ph hp trong mi l/m canh thang Mueller-Hinton v khoanh giy khuch tn i vi xt nghim gentamicin MIC v khng sinh S. aureus ATCC 25923

-Lactamase m tnh mecA m tnh t c gi tr trong xt nghim MIC do nhy cm vi hu ht cc khng sinh

Vi khun gram dng d mc

Ph lc C. (Tip) Chng QC

c im chng

Khng sinh

MIC

Xt nghim sng lc

Khc

M100-S21 S. aureus ATCC 29213 Cc chng sinh lactamase yu mecA m tnh Vi khun gram m d mc Cc khng sinh s dng cho vi khun dng trong khng b sinh hc Thch Oxacillin nh gi hm lng cation ph hp trong mi l/m canh thang Mueller-Hinton i daptomycin

S. aureus ATCC 43300 S. aureus ATCC BAA-1708

Khng Oxacillin, mecA dng tnh Khng mupirocin mc cao qua trung gian mup/A

Xt nghim vi khoanh giy Cefoxitin Xt nghim sng lc khng

Xt nghim MIC vi Thch Oxacillin Cefoxitin Xt nghim sng lc khng mupirocin mc

mupirocin mc cao cao S. pneumoniae Streptococcus spp. S. pneumoniae Streptococcus spp. N. meningitidis

S. pneumoniae ATCC 49619

Khng trung gian vi penicillin bi c ch bin i protein gn penicillin

N. meningitidis Cc khng sinh s dng cho vi khun dng trong khng b sinh hc

M100-S21 Cc chng QC b sung E. faecalis ATCC 29212

g

MIC ca ceftaroline

E. faecalis ATCC 33186

Thay th E. faecalis ATCC 29212 nh gi mi trng ph hp i vi xt nghim MIC cho sulfonamide hoc trimethoprimd

H. influenzae ATCC 10211

nh gi mi l m mi trng HTM v kh nng pht trin ca vi khun

M100-S21 K. pneumoniae ATCC BAA-1705

Chng sinh KPC

Xt nghim xc nh kiu hnh cc chng sinh carbapenemase

Xt nghim Hodge dng tnh

K. pneumoniae ATCC BAA-1706

Khng carbapenems bi cc c ch khc carbapenemase Xt nghim Hodge m tnh

(xt nghim Xt nghim xc nh kiu hnh cc chng sinh carbapenemas e (xt nghim Hodge iu

S. aureus ATCC BAA-976

Cha khng marcrolide duy nht qua trung gian msrA

chnh) nh gi xt nghim gn ng vi khoanh giy khng sinh erythromycin v clindamycin (Xt nghim vng D m tnh)

QC xem Bng 2CS4, 2C-S5, 3A, v 4A

M100-S21 S. aureus ATCC BAA-977

Cha khng qua trung gian ermA

nh gi xt nghim gn ng vi khoanh giy khng sinh erythromycin v clindamycin (Xt nghim vng D dng tnh)

QC thng qui i vi xt nghim clindamycin bng phng php MIC Xem Bng 2C-S4, 2CS5, 3A, v 4A

Ph lc C. (Tip) Ghi ch E. coli ATCC 35218 c xut lm chng chun i vi phi hp c ch -lactamase, nh cc phi hp cha axit clavulanic, sulbactam, hoc tazobactam. Chng ny cha plasmid m ha -lactamase (khng ESBL); do khng vi nhiu khng sinh khng bn vi penicillinase nhng nhy cm vi cc phi hp khng sinh -lactam/cht c ch -lactamase. Chng chun phi cha plasmid ny; tuy nhin plasmid c th mt trong qu trnh bo qun nhit m. m bo plasmid vn cn, kim tra chng vi khng sinh nhm -lactam n (hoc ampicillin, amoxicillin, piperacillin, hoc ticarcillin) v kim tra vi khng sinh phi hp -lactam/cht c ch -lactamase (v d, amoxicillin-clavulanate). Nu chng mt plasmid, chng s nhy cm vi khng sinh -lactam dng n c, v chng s khng c gi tr lm chng chun, cn s dng chng chun E. coli ATCC 35218 mi. Cn lu vic duy tr chng (v d, cy chuyn) v bo qun (v d, -60oC hoc thp hn) c bit quan trng i vi cc chng chun E. coli ATCC35218, K. pneumoniae ATCC 700603, v K. pneumoniae ATCC BAA-1705, bi v d mt plasmid m ha lactamase or carbapenemase. Mt plasmid dn n kt qu QC nm ngoi gii hn cho php, v d nh gim MICs ca E. coli ATCC 35218 i vi cc khng sinh nhm penicillin khng bn vi enzyme (v d, ampicillin, piperacillin, v ticarcillin), gim MICs ca K. pneumoniae ATCC 700603 vi cephalosporins v aztreonam, v xt nghim Hodge m tnh gi (MHT) i vi K. pneumoniae ATCC BAA-1705. Tr nn khng thuc khng sinh nhm -lactam sau khi cy chuyn nhiu ln. Hn ch bng cch cy chuyn chng mi t ng d tr t nht hng thng hoc bt c khi no xut hin s khng thuc. Cc im gii hn cn d c (Trn hoc bng 80% khun lc so vi chng chun) nu mi trng c cc mc thymidine chp nhn c. Rasheed JK, Anderson GJ, Yigit H, et al. Characterization of the extended-spectrum beta-lactamase reference strain, Klebsiella pneumoniae K6 (ATCC 700603), which produces the novel enzyme SHV-18. Antimicrob Agents Chemother. 2000;44:2382-2388.

a.

b.

c. d. e.

f.

g.

M100-S21 Queenan AM, Foleno B, Gownley C, Wira E, Bush K. Effects of inoculum and beta-lactamase activity in AmpC- and extended-spectrum betalactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae clinical isolates tested by using NCCLS ESBL methodology. J Clin Microbiol. 2004;42:269-275. Cc chng chun c kim tra thng xuyn (v d, hng ngy hoc hng tun) m bo h thng hot ng tt v cc kt qu ri vo cc gii hn c bit c lit k trong M100. Cc chng chun c xut trong ti liu ny cn c th nghim theo phng php khoanh giy khuch tn hoc MIC tham kho CLSI nh c trnh by y. i vi h thng xt nghim thng mi, tt c cc qui trnh QC cn tun th theo cc khuyn co ca nh sn xut. Cc chng chun QC b sung c dng nh gi cc c tnh ca mt xt nghim hoc h thng xt nghim trong cc tnh hung la chn c th hoc c th thay th chng QC. V d, Haemophilus influenzae ATCC10211 kh mc hn H. influenzae ATCC 49247 hoc H. influenzae ATCC 49766, v c dng m bo HTM c th h tr tt (cung cp dinh dng) cho s pht trin ca cc chng H. influenzae v H. parainfluenzae phn lp t lm sng. Cc chng QC b sung c th c cc c tnh nhy cm hoc khng c bit i vi mt hoc mt s xt nghim c lit k trong ti liu M02-A10 v M07-A8. Chng c th c dng nh gi xt nghim mi, tp hun cho ngi mi, nh gi nng lc. Cc chng chun QC b sung khng cn thit cho vo trong chng trnh QC AST hng ngy hoc hng tun.

M100-S21 Ph lc D. Bo co th nghim tnh nhy cm khng sinh ly tin i vi cc vi khun nhm Bacteroides fragilis Cc chng c phn lp t cc bnh vin Hoa K 01/01/2007-31/12/2009a

Cc vi khun k kh

% Nhy cm (%S) v % Khng (%R)c gi tr gii hn g/mL B. fragilis B. thetaiotaomi cron 872 342

%S

%R

%S

%R

%S % R

%S

% R

%S

% R

%S

%R % S

% R

%S

% R

%S

8/4 89 86

32/16 4 3

32/4 98 92

128/4 1 2

16 85 32

64 6 13

4 96 96

16 2 2

4 98 99

16 2 0

4 97 99

16 2 1

2 64 27

8 28 56

2 53 44

8 38 34

8 100 100

Metronidazoleb %R 32 0 0 39 46 50 55 38 100 100 100 100 100 0 0 0 0 0

B. ovatus B. vulgatus B. uniformis B. eggerthii Parabactero ides

67 70 60 58 111

93 67 87 95 69

2 6 2 0 11

93 100 91 93 91

2 0 0 0 2

37 83 42 98 41

15 4 13 2 16

98 98 97 100 97

0 2 0 0 0

100 98 100 100 100

0 2 0 0 0

100 98 98 100 100

0 2 2 0 0

54 49 35 29 30

39 51 52 55 41

43 43 35 28 54

Moxifloxacin

Clindamycin

Piperacillintazobactam

Meropenem

Ampicillinsulbactam

Ertapenem

Imipenem

Cefoxitin

S chng

M100-S21 distasonis Nhm B. 83 4 1 97 1 99 1 0 708 93 40 12 99 0 33 42 43 40 100 fragilis group khng k B. fragilis Nhm B. 86 4 2 1 98 1 1 0 1580 95 65 9 97 98 50 39 49 39 100 Fragilis (c 7 loi c lit k) a S liu c xy dng t cc chng ring l phn lp t bnh phm, gi n ba phng xt nghim tham kho: Tufts New England Medical Center, Boston, MA; Loyola University Medical Center, Maywood, IL; and R.M. Alden Research Laboratory, Culver City, CA. Xt nghim c tin hnh bng phng php pha long trn thch b Khng vi metronidazole him khi xy ra. c Khng trung gian khng c trnh by, nhng c th thu c bng cch tr %S v %R mi khng sinh

M100-S21

% Nhy cm (%S) v % Khng (%R)c Gi tr gii hn g/mL Prevotella spp. Fusobacteriu m nucleatumnec rophorum Cu khun Gram dng k khe Veillonella spp.b P. acnes Clostridium perfringens C. difficilec 173 44

%S %R

%S

%R

%S

% R

%S

% R 16

%S

% R

% R

%S

% R 2

%S

% R 8

%S

% R 8

%S

Metronidazoleb % R 32 8 100 100 0 0 98 1 86 3 100 100 11 97 0 0

8/4 98 100

32/1 6 1 0

32/4

128/4 1 0

16 64

16 16

0,5 40 100

99 100

99 100

1 0

100 100

0 0

100 100

0 0

1 0

49 0

66 100

30 0

Moxifloxacin

Clindamycin

Piperacillintazobactam

Meropenem

Ampicillinsulbactam

Ertapenem

Imipenem

Penicillin/ ampicillin

Cefoxitin

S chng

Ph lc E. Bo co th nghim tnh nhy cm khng sinh ly tin i vi cc vi khun k kh khng bao gm nhm Bacteroides fragilis Cc chng c phn lp t cc bnh vin Hoa K 01/01/2007-31/12/2009a Cc vi khun k kh

59 95

24 5

168

98

100

100

100

100

96

78

20

82

11

28 34 73 56

100 100 100 100

0 0 0 0

61 100 100 100

7 0 0 0

100 100 100 0

0 0 0 100

100 100 100 100

0 0 0 0

100 100 100 20

0 0 0 18

0 0 0 0

57 100 100 0

28 0 0 79

89 91 96 5

7 3 0 79

79 100 99 78

14 0 1 22

Cc 43 100 0 100 0 47 26 100 0 100 0 0 79 9 56 21 74 12 Clostridium spp. khc a S liu c xy dng t cc chng ring l phn lp t bnh phm, gi n ba phng xt nghim tham chiu: Tufts New England Medical Center, Boston, MA; Loyola University Medical Center, Maywood, IL; and R.M. Alden Research Laboratory, Culver City, CA. Xt nghim c tin hnh bng phng php pha long trn thch b s lng c cng tnh ly tin t hn so vi ti liu CLSI M39 khuyn co vi 30 chng c C. difficile c phn lp t bnh phm phn; nhng kt qu ny khng bo hm cho tc dng nhim trung ngoi ng tiu ha. MIC ca Vancomycin vi cc chng ny < 4 g/mL. d Khng trung gian khng c trnh by, nhng c th rt ra bng cch tr %S v %R mi khng sinh e Cu khun Gram dng k kh bao gm cc loi: Peptococcus, Peptostreptococcus, Finegoldia, Peptoniphilus, v Anaerococcus. Bng ch thch I (Phn 1). -Lactams: Nhm v phn nhm v tn gc Nhm khng sinh Penicillinse Phn nhm khng sinh Penicillina Aminopenicillina Ureidopenicillina
a

M100-S21 100 0

Cc khng sinh c th; tn gc Penicillin Amoxicillin Ampicillin Azlocillin Mezlocillin Piperacillin

Carboxypenicillin

Carbenicillin
b

Cc penicillin bn vi Penicillinase

Ticarcillin Cloxacillin Dicloxacillin Methicillin Nafcillin Oxacillin

Amidinopenicillin

Mecillinam

M100-S21 Phi hp -Lactam/c ch -lactamase Amoxicillin-axit clavulanic Ampicillin-sulbactam Piperacillin-tazobactam Ticarcillin- axit clavulanic Cephems (ng tim) Cephalosporin I c, e Cefazolin Cephalothin Cephapirin Cephradine Cephalosporin II
c, e

Cefamandole Cefonicid Cefuroxime (ng tim)

Cephalosporin III c, e

Cefoperazone Cefotaxime Ceftazidime Ceftizoxime

Cephalosporin IV c, e Cephalosporins c hot tnh khng MRSA Cephamycind

Ceftriaxone Cefepime Ceftaroline Ceftobiprole Cefmetazole Cefotetan Cefoxitin

Oxacephem

Moxalactam

M100-S21 Cephems (ng ung) Cephalosporin

e

Cefaclor Cefadroxil Cefdinir Cefditoren Cefetamet Cefxime Cefpodoxime Cefprozil Ceftibuten Cefuroxime (oral) Cephalexin Cephradine

Carbacephem Monobactams Penems

e

Carbapenem

Loracarbef Aztreonam Doripenem Ertapenem Imipenem Meropenem

Penem

Razupenem Faropenem Sulopenem

a b

Khng bn vi penicillinase; b thy phn bi penicilinase do t cu sinh ra. Khng b thy phn bi penicillinase t cu.

M100-S21 Cephalosporin th h I, II, III, IV i khi c vit l 1, 2, 3, 4 tng ng. Cephalosporin th h III, IV cng c gi l cephalosporin ph rng. Thut ng ny khng m ch hot tnh khng vi khun gram m sinh ESBL. d Mc d thng c qui l khng sinh cephalosporin th h 2, cephamycin khng c bao gm vi cc khng sinh cephalosporin khc khi cp n cc chng sinh ESBL. e i vi tt c cc chng sinh ESBL, c kt qu v bo co khng vi cc khng sinh trong nhm hoc phn nhm ny.
c

M100-S21 Bng ch thch I (Phn 2). Cc khng sinh khc-lactams: Nhm v phn nhm, tn gc Nhm khng sinh Aminocyclitols Phn nhm khng sinh Cc khng sinh c th; Tn gc Spectinomycin Trospectinomycin Aminoglycosides Amikacin Gentamicin Kanamycin Netilmicin Streptomycin Tobramycin Ansamycins Quinolones Quinolone Rifampin Cinoxacin Garenoxacin Nalidixic acid Ruoroquinolone Besifloxacin Ciprofloxacin Clinafloxacin Enoxacin Fleroxacin Gatifloxacin Gemifloxacin Grepafloxacin Levofloxacin

M100-S21 Lomefloxacin Moxifloxacin Norfloxacin Ofloxacin Sparfloxacin Trovafloxacin UliAoxacin (prulifloxacin) c ch con ng chuyn ha folate lclaprim Sulfonamides Trimethoprim Trimethoprim-sulfamethoxazole Fosfomycins Glycopeptides Glycopeptide Lipoglycopeptide Fosfomycin Vancomycin Dalbavancin Oritavancin Teicoplanin Telavancin Glycylcyclines Ketolides Lincosamides Lipopeptides Polymyxins Tigecycline Telithromycin Clindamycin Daptomycin Colistin Polymyxin B Marcrocyclic Fidaxomicin

M100-S21 Macrolides Azithromycin Clarithromycin Dirithromycin Erythromycin Nitrofurans Nitroimidazoles Oxazolidinones Phenicols Pseudomonic acid Streptogramins Nitrofurantoin Metronidazole Linezolid Chloramphenicol Mupirocin Linopristin-flopristin Quinupristin-dalfopristin Tetracyclines Doxycycline Minocycline Tetracycline

M100-S21 Bng ch thch II. Ch vit tt/ng dng/Phn nhm i vi cc khng sinh c lit k trong M100-S20 Khng sinh Amikacin Ch vit tta PO AN, AK, Ak, AMI, AMK Amoxicillin AMX, Amx, AMOX, AC Amoxicillin-clavulanic axit AMC, Amc, A/C, AUG, Aug, XL, AML X -Lactam/c ch lactamase X Penicillin ng dng b IM IV X X Phn nhm Cc b Aminoglycoside

Ampicillin Ampicillin-sulbactam

AM, Am, AMP SAM, A/S, AMS, AB

X X

Penicillin -Lactam/c ch lactamase

Azithromycin Azlocillin Aztreonam

AZM, Azi, AZI, AZ AZ, Az, AZL ATM, AZT, Azt, AT, AZM

X X

X X X

Macrolide Penicillin Monobactam

Besitloxacin Carbenicillin (mui indanyl) Carbenicillin Cefaclor

BES CB, Cb, BAR X X X

Fluoroquinolone Penicillin

CEC, CCL, Cfr, FAC, CF

Cephem

M100-S21 Cefadroxil Cefamandole Cefazolin Cefdinir CFR, FAD MA, CM, Cfm, FAM cz, CFZ, Cfz, FAZ, KZ CDR, Cdn, DIN, CD, CFD Cefditoren Cefepime Cetetamet Cetixime Cefmetazole Cefonicid Cefoperazone CDN FEP, Cpe, PM, CPM CAT, FET CFM, FIX, Cfe, IX CMZ, CMZS, CMT CID, Cfc, FON, CPO CFP, Cfp, CPZ, PER, FOP, CP Cetotaxime Cefotetan CTX, TAX, Cft, FOT, CT CTT, CTN, ctn, CTE, TANS, CN Cefoxitin Cefpodoxime Cefprozil Ceftaroline Ceftazidime Ceftibuten Ceftizoxime FOX, cx, Cfx, FX CPD, Cpd, POD, PX CPR, CPZ, FP CPT CAZ, Caz, TAZ, TZ CTB, TIB, CB ZOX, CZX, Cz, Cz, CTZ, TIZ Ceftobiprole BPR X Cephem X X X X X X X X X X Cephem Cephem Cephem Cephem Cephem Cephem Cephem X X X X Cephem Cephem X X X X X X X X X X X Cephem Cephem Cephem Cephem Cephem Cephem Cephem X X X X X X Cephem Cephem Cephem Cephem

M100-S21 Ceftriaxone CRO, CTR, FRX, Cax, AXO, TX Cefuroxime (ung) Ceturoxime (tim) CXM, CFX, ROX, Crm, FUR, XM Cephalexin Cephalothin CN, LEX, CFL CF, Cf, CR, CL, CEP, CE, KF X X Cephem Cephem X X X Cephem X X Cephem

M100-S21 Bng ch thch II. (Tip) Khng sinh Tn vit tta PO Cephapirin Cephradine Chloramphenicol Cinoxacin Ciprotloxacin Clarithromycin Clinafloxacin Clindamycin Colistin Dalbavancin Daptomycin Dicloxacillin Dirithromycin Doripenem Ertapenem Erythromycin Faropenem Fidaxomicin Fleroxacin Fosfomycin Garenoxacin Gatitloxacin CP, HAP RAD, CH C, CHL, CL CIN, Cn CIP, Cp, Cl CLR, CLM, CLA, CFN, CLX, LF CC, CM, CD, Cd, CLI, DA CL, CS, CT DAL DAP DX, DIC DTM, DT DOR ETP E, ERY, EM FAR, FARO FDX FLE, Fle, FLX, FO FOS, FF, FO, FM GRN GAT ng dngb IM X X X X X X X X X X IV X Ti ch Cephem Cephem Phenicol Quinolone Fluoroquinolone Macrolide Fluoroquinolone Lincosamide Lipopeptide Glycopeptide Lipopeptide Penicillin Macrolide Carbapenem Carbapenem Macrolide Penem Macrocyclic Ruoroquinolone Fosfomycin Quinolone Fluoroquinolone Nhm

X X X X X X

X X X X X X X X X X X X X

X X X

M100-S21 Gemitloxacin Gentamicin Grepatloxacin lclaprim Imipenem Kanamycin Levofloxacin GEM GM, Gm, CN, GEN GRX, Grx, GRE, GP ICL IPM, IMI, Imp, IP K, KAN, HLK, KM LVX, Lvx, LEV, LEVO, LE Linezolid LinopristinLometloxacin Loracarbef Mecillinam Meropenem Methicillin Metronidazole Mezlocillin Minocycline Moxalactam Moxitloxacin Mupirocin Nafcillin Nalidixic acid Netilmicin LNZ, LZ, LZD LFE LOM, Lmf
LOR, Lor, LO

X X X X X X X X X X

Ruoroquinolone Aminoglycoside Fluoroquinolone c ch con ng Folate Carbapenem Aminoglycoside Fluoroquinolone

X X X X X

Oxazolidinone Streptogramin Ruoroquinolone Cephem Penicillin Carbapenem Penicillin Nitroimidazole Penicillin Tetracycline Cephem Fluoroquinolone Axit pseudomonic Penicillin Quinolone Aminoglycoside

MEC MEM, Mer, MERO, MRP, DP, MET, ME, se MTZ MZ, Mz, MEZ MI, MIN, Min, MN, MNO, MOX MXF MUP, MOP, MU NF, NAF, Nai NA, NAL NET, Nt, NC

X X X X X X X X X X X X X X X X X X X

M100-S21 Nitrofurantoin F/M, FD, Fd, FT, NIT, NI, F Norfloxacin Ofloxacin Oritavancin Oxacillin NOR, Nxn, NX OFX, OFL, OA, OF ORI OX, Ox, OXS, OXA X X X X X X X X Fluoroquinolone Fluoroquinolone Lipoglycopeptide Penicillin X Nitrofurantoin

M100-S21 Bng ch gii II. (Tip) Khng sinh Penicillin Piperacillin Piperacillin-tazobactam Polymyxin B Quinupristin-dalfopristin Razupenem Ritampin Sparfloxacin Spectinomycin Streptomycin Streptomycin synergy Tn vit tta p, PEN, PV PIP, Pl, PP, Pi TZP, PTZ, P/T, PTc PB SYN, Syn, QDA, RP RZM RA, RIF, Rif, RI, RD SPX, Sfx, SPA, SO SPT, SPE, SC S, STR, StS, SM, ST2000, HLS Sulfonamides SSS, S3 X X i lp con ng Folate (ch i vi mt s PO) Sulopenem Teicoplanin SLP, SULO TEO, TPN, Tei, TEI, TP, TPL Telavancin Telithromycin Tetracycline Ticarcillin TLV TEL TE, Te, TET, TC TIC, TC, TI, Ti X X X X X X Glycopeptide Ketolide Tetracycline Penicillin X X X X Penem Glycopeptide PO X ng dng b IM IV X X X X X X X X X X X X X Nhm Penicillin Penicillin -Lactam/c ch -lactamas Lipopeptide Streptogramin Carbapenem Ansamycin Ruoroquinolone Aminocyclitol Aminoglycoside

X X

M100-S21 Ticarcillin-clavulanic acid Tigecycline Tobramycin Trimethoprim Trimethoprim-sulfamethoxazole Trospectinomycin Trovaloxacin Ulifloxacin (prulifloxacin) Vancomycin TIM, Tim, T/C, TCC, TLc TGC NN, TM, TO, To, TOB TMP, T, TR, w SXT, SxT, T/S, TS, COT TVA, Tva, TRV, TV PRU VA, Va, VAN X X X X X X X X X X X X X X -Lactam/c ch -lactamase Glycylcycline Aminoglycoside c ch con ng folate c ch con ng folate Aminocyclitol Ruoroquinolone Fluoroquinolone Glycopeptide

PO = mi OS (ung); IM = tim bp; IV= Tim tnh mch. Cc ch vit tt c s dng cho mt hoc nhiu sn phm chn on Hoa K. Nu khng c sn phm chn on no c sn, ch vit tt l ca nh sn xut. b Sn c Hoa K.
a

M100-S21 Ph lc III. Danh sch cc ch vit tt dng cho hn mt khng sinh Hoa K, cc sn phm chn on Ch vit tt AZM AZ CB, Cb C CFR, Cfr C CF, Cf C CM CFM, Cfm C CZ, Cz C CD, Cd C CPZ CP, Cp C CN, Cn C CFX, Cfx C CL CH DX FO SC SO TC Azithromycin Azithromycin Ceftibuten Cefaclor Cefaclor Clindamycin Cefixime Ceftizoxime Clindamycin Cefprozil Cephapirin Cephalexin Cefoxitin Cephalothin Clarithromycin Doxycycline Fleroxacin Spectinomycin Sparfloxacin Tetracycline Khng sinh