革兰阴性菌耐药折点问题实用版课件.ppt
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1、革兰阴性菌耐药折点问题文档ppt2012主要变化v肠杆菌科修订厄他培南折点增加环丙沙星折点(伤寒沙门菌和胃肠外沙门菌)v绿脓杆菌降低 哌拉西林、哌拉西林/他唑巴坦、替卡西林、替卡西林/克拉维酸折点降低 亚胺培南、美罗培南折点;增加多利培南折点v葡萄球菌增加金葡菌青霉素抑菌圈周边试验检测(penicillin disk zone edge test)-内酰胺酶产生M100-S22.P22CLSI Breakpoint Additions/Revisions Since 2010Antimicrobial AgentDate of Revision*(M100 version)CommentsEn
2、terobacteriaceae AztreonamJanuary 2010(M100-S20)CefazolinJanuary 2010(M100-S20)January 2011(M100-S21)Breakpoints were revised twice since 2010CefotaximeJanuary 2010(M100-S20)CeftazidimeJanuary 2010(M100-S20)CeftizoximeJanuary 2010(M100-S20)CeftriaxoneJanuary 2010(M100-S20)DoripenemJune 2010(M100-S20
3、U)No previous CLSI breakpoints for doripenemErtapenemJune 2010(M100-S20U)January 2012(M100-S22)Breakpoints were revised twice since 2010.ImipenemJune 2010(M100-S20U)MeropenemJune 2010(M100-S20U)Cipro Salmonella onlyJanuary 2012(M100-S22)CLSI Breakpoint Additions/Revisions Since 2010Antimicrobial Age
4、ntDate of Revision*(M100 version)CommentsPseudomonas aeruginosaPiperacillin-tazobactamJanuary 2012(M100-S22)Ticarcillin-clavulanateJanuary 2012(M100-S22)TicarcillinJanuary 2012(M100-S22)PiperacillinJanuary 2012(M100-S22)肠杆菌科:碳靑霉烯类美国碳靑霉烯类耐药肠杆菌科(CRE)的分布黄色:黄色:KPC酶;酶;蓝点:蓝点:IMP、VIM黄点:黄点:NDMCLSI使用以下数据建立/修
5、订折点v“野生菌群”或常规菌群的MIC分布野生菌群=未携带获得性“耐药”机制v与临床预后相关的MIC对于老药很少有“新”数据 v药物代谢-药效学(PK-PD)分析Time(hours)Organism%Time MIC肠杆菌科35%绿脓30%DMID 2009年Piperacillin-tazobactam6 Carbapenemases(metallo-lactamases)(24)解释标准基于每6小时一次,每次500mg或每8小时一次,每次1g的给药方案。1Corresponding disk diffusion breakpoints also revised5 MHT same res
6、ult with ertapenem and meropenem(and imipenem)disksCLSI vs FDA Interpretive CriteriaPages 52-60.*目前和FDA折点相同January 2012(M100-S22)January 2010(M100-S20)Pages 52 and 56.and Ciprofloxacin药敏试验折点建立和抗菌药物的PK/PDTicarcillin-clavulanic acid临床实验室可以使用 CLSI 或 FDA 折点Red=isolates with acquired“R”mechanism3 Limbago
7、,BM.2012年CLSI 绿脓杆菌折点变化Staphylococcus spp.CLSI Breakpoint Additions/Revisions Since 2010CLSI DocumentMIC(g/ml)Disk Diffusion(mm)SuscIntResSuscIntResM100-S20(Jan.2010)*2481916-1815M100-S20U(June 2010)0.250.512320-2219M100-S22(Jan 2012)*0.51.022219-2118肠杆菌科 厄他培南CLSI 折点更新过程*目前和目前和FDA折点相同折点相同为何多次进行修改?v20
8、11 breakpoints primarily based on:MIC distributionsPK/PD(conservatively went with 0.25 g/ml)Very limited clinical data(no patients with MICs at 0.5 g/ml)v2012 breakpoints primarily based on:Additional surveillance data showed isolates with MICs of 0.5 g/ml did not have carbapenemasesFurther review o
9、f PK/PDAdditional clinical data(including ESBL-producing E.coli with 0.5 g/ml MICs suggested clinical response)Also,lowest ertapenem concentration on some commercial panels is 0.5 g/ml thus allowing labs to use CLSI ertapenem breakpoints(following verification)if breakpoint is 0.5 g/ml but not if 0.
10、25 g/ml510152025303540Ertapenem Disk Zone Diameter(mm)8Ertapenem MIC(g/ml)11111111111111111111111111111122222222222222222333333333334444444455556666677777777788999910101213131415192024263137374751545664101Ertapenem MIC vs.Disk(All)n=948y=16.3-0.37xr=-0.93Susc.:0.5 g/ml/22 mm Res.:2 g/ml/18 mm VM=0.0
11、%Ma=0.0%Mi=6.1%FOR NEW BREAKPOINTS APPROVED June 2011Modified Hodge Test(MHT)(Table 2A Supplemental Table 2 and 3)“NOTE:Not all carbapenemase-producing isolates of Enterobacteriaceae are MHT positive and MHT-positive results may be encountered in isolates with carbapenem resistance mechanisms other
12、than carbapenemase production.”4 Select CRE Examples:Carbapenem MICs&MHT&-Lactam Resistance MechanismOrganismMIC(g/ml)1MHTResistancemechanismErtapImipMeroE.coli216 R4 R4 RPos4 Plasmid ampCK.pneumoniae216 R0.25 S8 RPos5 ESBL blashvE.coli316 R8 R16 RNeg5 NDM-16K.pneumoniae32 R1 S2 IPos5 IMP-461 Interp
13、reted with current breakpoints2 Anderson,KF et al.2009.ICAAC.D-719.3 Limbago,BM.CLSI Agenda book.January 2011.4 MHT positive only with ertapenem disk5 MHT same result with ertapenem and meropenem(and imipenem)disks Carbapenemases(metallo -lactamases)旧的模式新的模式降低 哌拉西林、哌拉西林/他唑巴坦、替卡西林、替卡西林/克拉维酸折点Pseudomo
14、nas aeruginosaaeruginosa with reduced susceptibility to piperacillin-tazobactamComment(23)Page 47.January 2011(M100-S21)Pseudomonas aeruginosaNew M100-S221typhi and ExtraintestinalPiperacillin-tazobactam MIC distribution exampleaureus QC:Neg-ATCC 259235 g/ml MICs suggested clinical response)(24)解释标准
15、基于每6小时一次,每次500mg或每8小时一次,每次1g的给药方案。Policies in other countries may vary.January 2011(M100-S21)-lactamase negativeaureus QC:Neg-ATCC 25923Isolates A-D are allISO15189与微生物检验3 Limbago,BM.CLSI Agenda book.(22)解释标准基于每)解释标准基于每8小时一次,每次小时一次,每次500mg的给药方案。的给药方案。(23)解释标准基于每天一次,每次)解释标准基于每天一次,每次1g的给药的给药方案。方案。(24)
16、解释标准基于每)解释标准基于每6小时一次,每次小时一次,每次500mg或每或每8小时一次,每次小时一次,每次1g的给药方案。的给药方案。(25)解释标准基于每)解释标准基于每8小时一次,每次小时一次,每次1g的的给药方案。给药方案。碳青霉烯类药物MIC 报告策略例#1例#2美罗培南 MIC(g/ml)4422改良霍奇试验*阳性阴性 阳性阴性 报告(旧折点)耐药敏感耐药敏感报告(新折点)*耐药耐药中介中介敏感中介耐药旧4816新 124如果用如果用 旧折点旧折点和和碳青霉烯酶筛选试碳青霉烯酶筛选试验阳性验阳性如果用如果用当前折点当前折点和和 需要流行病学的需要需要流行病学的需要进行进行MHT进行
17、进行MHT为何做为何做 MHT?绿脓杆菌Pseudomonas aeruginosa Breakpoint(MIC g/ml)RevisionsAgentOld(M100-S21)New M100-S221SuscIntResSuscIntResPiperacillin 64-1281632-64128Piperacillin-tazobactam64/4-128/416/432/4-64/4128/4Ticarcillin64-1281632-64128Ticarcillin-clavulanate64/2-128/216/232/2-64/2128/2Pseudomonas aerugin
18、osa 2012年CLSI 绿脓杆菌折点变化BPiperacillin-tazobactam 211520 14 16/432/464/4 128/4(7)Interpretive criteria for piperacillin(alone or with tazobactam)are based on a piperacillin dosage regimen of at least 3 g every 6 h.OTicarcillin-clavulanic acid 241623 15 16/232/264/2 128/2(8)Interpretive criteria for tic
19、arcillin(alone or with clavulanate)are based on a ticarcillin dosage regimen of at least 3 g every 6 h.BDoripenem 191618 15 24 8(12)Interpretive criteria for doripenem are based on a dosage regimen of 500 mg every 8 h.BImipenem/Meropenem 191618 15 24 8(13)Interpretive criteria for imipenem and merop
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