革兰阴性菌耐药折点问题实用版课件

革兰阴性菌耐药折点问题文档ppt革兰阴性菌耐药折点问题文档ppt1M100-S22PartialTableofContentsM100-S22.Page9.4M100-S22M100-S22.Page9.42更新的的总结

M100-S22.Page13.5更新的M100-S22.Page13.532012主要变化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）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；增加多利培南折点葡萄球菌

增加金葡菌青霉素抑菌圈周边试验检测（penicillindiskzoneedgetest）β-内酰胺酶产生New!62012主要变化肠杆菌科New!64M100-S22.P222010年后折点变化过程New!7M100-S22.P222010年后折点变化过程New!75CLSIBreakpointAdditions/RevisionsSince2010AntimicrobialAgentDateofRevision*(M100version)CommentsEnterobacteriaceaeAztreonamJanuary2010(M100-S20)CefazolinJanuary2010(M100-S20)January2011(M100-S21)Breakpointswererevisedtwicesince2010CefotaximeJanuary2010(M100-S20)CeftazidimeJanuary2010(M100-S20)CeftizoximeJanuary2010(M100-S20)CeftriaxoneJanuary2010(M100-S20)DoripenemJune2010(M100-S20U)NopreviousCLSIbreakpointsfordoripenemErtapenemJune2010(M100-S20U)January2012(M100-S22)Breakpointswererevisedtwicesince2010.ImipenemJune2010(M100-S20U)MeropenemJune2010(M100-S20U)Cipro–SalmonellaonlyJanuary2012(M100-S22)CLSIBreakpointAdditions/Re6CLSIBreakpointAdditions/RevisionsSince2010AntimicrobialAgentDateofRevision*(M100version)CommentsPseudomonasaeruginosaPiperacillin-tazobactamJanuary2012(M100-S22)Ticarcillin-clavulanateJanuary2012(M100-S22)TicarcillinJanuary2012(M100-S22)PiperacillinJanuary2012(M100-S22)CLSIBreakpointAdditions/Re7肠杆菌科：

碳靑霉烯类

肠杆菌科：

碳靑霉烯类

8革兰阴性菌耐药折点问题实用版课件9美国碳靑霉烯类耐药肠杆菌科（CRE）的分布黄色：KPC酶；蓝点：IMP、VIM黄点：NDM美国碳靑霉烯类耐药肠杆菌科（CRE）的分布黄色：KPC酶；10CLSI使用以下数据建立/修订折点“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”机制与临床预后相关的MIC对于老药很少有“新”数据

药物代谢-药效学(PK-PD)分析CLSIM23-A3(2008)“体外药敏实验标准和质量控制参数的发展;批准的指南”描述了CLSI建立和修订折点的过程。CLSI使用以下数据建立/修订折点“野生菌群”或常规菌11Piperacillin-tazobactam

MICdistributionexampleBlue=wildtypeisolatesRed=isolateswithacquired“R”10Piperacillin-tazobactamMICdi12SerumConcentration(µg/ml)Time(hours)MICTimeaboveMICdosedoseCmax(peakconcentration)PK/PDGoal(“Target”)forβ-lactams=(%T>MIC)12Organism%Time>MIC肠杆菌科35%绿脓30%SerumConcentration(µg/ml)Tim13DMID2009年DMID2009年14革兰阴性菌耐药折点问题实用版课件15革兰阴性菌耐药折点问题实用版课件16Piperacillin-tazobactam6Carbapenemases(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。1 Correspondingdiskdiffusionbreakpointsalsorevised5MHTsameresultwithertapenemandmeropenem(andimipenem)disksCLSIvsFDAInterpretiveCriteriaPages52-60.*目前和FDA折点相同January2012(M100-S22)January2010(M100-S20)Pages52and56.andCiprofloxacin药敏试验折点建立和抗菌药物的PK/PDTicarcillin-clavulanicacid临床实验室可以使用CLSI或FDA折点Red=isolateswithacquired“R”mechanism3Limbago,BM.2012年CLSI绿脓杆菌折点变化Staphylococcusspp.CLSIBreakpointAdditions/RevisionsSince2010Piperacillin-tazobactam17CLSIDocumentMIC(µg/ml)DiskDiffusion(mm)SuscIntResSuscIntResM100-S20(Jan.2010)*≤24≥8≥1916-18≤15M100-S20U(June2010)≤0.250.5≥1≥2320-22≤19M100-S22(Jan2012)**≤0.51.0≥2≥2219-21≤18肠杆菌科–厄他培南

CLSI折点更新过程*目前和FDA折点相同NewNew!28CLSIDocumentMIC(µg/ml)DiskD18为何多次进行修改?2011breakpointsprimarilybasedon:MICdistributionsPK/PD(conservativelywentwith≤0.25µg/ml)Verylimitedclinicaldata(nopatientswithMICsat0.5µg/ml)2012breakpointsprimarilybasedon:AdditionalsurveillancedatashowedisolateswithMICsof0.5µg/mldidnothavecarbapenemasesFurtherreviewofPK/PDAdditionalclinicaldata(includingESBL-producingE.coliwith0.5µg/mlMICssuggestedclinicalresponse)Also,lowestertapenemconcentrationonsomecommercialpanelsis0.5µg/mlthusallowinglabstouseCLSIertapenembreakpoints(followingverification)ifbreakpointis≤0.5µg/mlbutnotif≤0.25µg/ml29为何多次进行修改?2011breakpointsprim19CLSIAgendaBookJune201130CLSIAgendaBookJune20113020CLSIAgendaBookJune201131CLSIAgendaBookJune20113121Susc.:≤0.5µg/ml/≥22mmRes.:≥2µg/ml/≤18mmVM=0.0%Ma=0.0%Mi=6.1%FORNEWBREAKPOINTSAPPROVEDJune2011Susc.:≤0.5µg/ml/≥22mmFOR22ModifiedHodgeTest(MHT)

(Table2ASupplementalTable2and3)

“NOTE:Notallcarbapenemase-producingisolatesofEnterobacteriaceaeareMHTpositiveandMHT-positiveresultsmaybeencounteredinisolateswithcarbapenemresistancemechanismsotherthancarbapenemaseproduction.”

M100-S22.Table2ASupplementalTables2and3.Pages53and57.New!36ModifiedHodgeTest(MHT)

(Ta234SelectCREExamples:CarbapenemMICs&MHT&-LactamResistanceMechanismOrganismMIC(µg/ml)1MHTResistancemechanismErtapImipMeroE.coli2>16R4R4RPos4

PlasmidampCK.pneumoniae2>16R≤0.25S8RPos5

ESBLblashvE.coli3>16R8R>16RNeg5

NDM-16K.pneumoniae32R1S2IPos5

IMP-461Interpretedwithcurrent

breakpoints2Anderson,KFetal.2009.ICAAC.D-719.3Limbago,BM.CLSIAgendabook.January2011.4MHTpositiveonlywithertapenemdisk5MHTsameresultwithertapenemandmeropenem(andimipenem)disks6Carbapenemases(metallo-lactamases)394SelectCREExamples:Carbape24进行耐药机制的初筛试验(MIC升高至接近“敏感”折点为“可疑”)进行耐药机制的特异确证试验若检测到耐药机制则更改药敏报告发现一种新型β-内酰胺酶(如ESBL或碳青霉烯酶)旧的模式ESBLMHTCourtesyofDr.JeanPatelCDC进行耐药机制的初筛试验进行耐药机制的特异确证试验若检测到耐药25新的模式进行药敏试验并且使用新的“降低的”折点以治疗为目的报告药敏结果–不更改“敏感”结果仅以感染控制和流行病学研究为目的进行特殊的耐药机制检测试验分离出肠杆菌科菌CourtesyofDr.JeanPatelCDC新的模式进行药敏试验并且使用以治疗为目的报告药敏结果仅以26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Pseudomonasaeruginosaaeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Comment(23)Page47.January2011(M100-S21)PseudomonasaeruginosaNewM100-S221typhiandExtraintestinalPiperacillin-tazobactamMICdistributionexampleaureusQC:

Neg-ATCC259235µg/mlMICssuggestedclinicalresponse)（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。Policiesinothercountriesmayvary.January2011(M100-S21)β-lactamasenegativeaureusQC:

Neg-ATCC25923IsolatesA-DareallISO15189与微生物检验3Limbago,BM.CLSIAgendabook.CLSIM100-S20-U表1A修订的碳青霉烯类药物折点和对应的药物剂量SIRSIR（22）解释标准基于每8小时一次，每次500mg的给药方案。（23）解释标准基于每天一次，每次1g的给药方案。（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。（25）解释标准基于每8小时一次，每次1g的给药方案。降低哌拉西林、哌拉西林/他唑巴坦、替卡西林、替卡西林/克拉27M100-S22.Table2ASupplementalTables2and3.Pages52-60.(旧折点)(当前折点)MHT检测碳青霉烯酶35M100-S22.(旧折点)(当前折点)MHT检测碳青霉烯28碳青霉烯类药物MIC

报告策略例#1例#2美罗培南MIC(µg/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*对常规病人的报告不必做改良霍奇试验;可以为感染控制目的而进行该试验但不要把“敏感”或“中介”改为“耐药”敏感中介耐药旧≤48≥16新≤12≥4折点(µg/ml)碳青霉烯类药物MIC

报告策略例#1例#2美罗培南M29如果用旧折点和碳青霉烯酶筛选试验阳性如果用当前折点和需要流行病学的需要进行MHT进行MHT为何做MHT?M100-S22.Comment(23)Page47.Table2ASupplementalTables2and3.Pages52and56.40如果用如果用进行MHT进行MHT为何做MHT?M100-30革兰阴性菌耐药折点问题实用版课件31绿脓杆菌57绿脓杆菌5732Pseudomonasaeruginosa

Breakpoint(MICµg/ml)RevisionsAgentOld(M100-S21)NewM100-S221SuscIntResSuscIntResPiperacillin≤64-≥128≤1632-64≥128Piperacillin-tazobactam≤64/4-≥128/4≤16/432/4-64/4≥128/4Ticarcillin≤64-≥128≤1632-64≥128Ticarcillin-clavulanate≤64/2-≥128/2≤16/232/2-64/2≥128/21 Correspondingdiskdiffusionbreakpointsalsorevised

M100-S22.Table2B-1.Page63.New!58Pseudomonasaeruginosa

Break33Pseudomonasaeruginosa

M100-S22.Table2B-1.Page63.Dosagecomments(3gevery6halsoforpiperacillinandforticarcillin)59PseudomonasaeruginosaM100-S2342012年CLSI绿脓杆菌折点变化BPiperacillin-tazobactam

2115–20

14

16/432/4–64/4

128/4(7)Interpretivecriteriaforpiperacillin(aloneorwithtazobactam)arebasedonapiperacillindosageregimenofatleast3gevery6h.OTicarcillin-clavulanicacid

2416–23

15

16/232/2–64/2

128/2(8)Interpretivecriteriaforticarcillin(aloneorwithclavulanate)arebasedonaticarcillindosageregimenofatleast3gevery6h.BDoripenem

1916–18

15

24

8(12)Interpretivecriteriafordoripenemarebasedonadosageregimenof500mgevery8h.BImipenem/Meropenem

1916–18

15

24

8(13)Interpretivecriteriaforimipenemandmeropenemarebasedonadosageregimenof1gevery8h.2012年CLSI绿脓杆菌折点变化BPiperacilli35SectionIII. Therapy-RelatedComments

“Incaseswherespecificdosageregimensareimportantforproperapplicationofbreakpoints,thedosageregimenislisted.Thesedosageregimencommentsarenotintendedforuseonindividualpatientreports.”M100-S22.Instructions.Page28.New!60SectionIII. Therapy-RelatedC36最新CLSI推荐的分枝杆菌、奴卡菌、其他需氧放线菌的药敏试验规程AntimicrobialAgentβ-lactamasepositive临床实验室可以使用CLSI或FDA折点ISO15189与微生物检验SerumConcentration(µg/ml)DosagecommentsSIR增加金葡菌青霉素抑菌圈周边试验检测（penicillindiskzoneedgetest）β-内酰胺酶产生Ticarcillin-clavulanateJanuary2010(M100-S20)CLSIAgendaBookJune2011CLSIBreakpointAdditions/RevisionsSince2010Enterobacteriaceae进行耐药机制的初筛试验Therapy-RelatedComments*目前和FDA折点相同Pages53and57.January2012(M100-S22)Salmonellaspp.Pseudomonasaeruginosa

Penicillins+/-β-lactamaseInhibitors

P.aeruginosabreakpointsoriginallysethigherthanthoseforEnterobacteriaceaebasedinpartonFDAlabelnotingthatthesedrugsshouldbeconsideredincombinationtherapywithaminoglycosideDeletedcommentfromTable2B-1-“Rx:Thesusceptiblecategoryforpenicillins,β-lactam/β-lactamaseinhibitorsimpliestheneedforhigh-dosetherapyforseriousinfectionscausedbyP.aeruginosa.Fortheseinfections,monotherapyhasbeenassociatedwithclinicalfailure”P.aeruginosaMICbreakpointsarenowthesameasthoseforEnterobacteriaceae(slightdifferencesindiskdiffusionbreakpoints)61最新CLSI推荐的分枝杆菌、奴卡菌、其他需氧放线菌的药敏试验37Outcomesofbacteremia(N=34episodes)duetoP.aeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Tametal.2008.ClinInfectDis.46:862.22.2%85.7%30.0%20.5%Clinicaldatasuggestformerbreakpointstoohigh!62Outcomesofbacteremia(N=34e38Pseudomonasaeruginosa

Breakpoint(MICµg/ml)Revisions

AgentOld(M100-S21)NewM100-S221SuscIntResSuscIntResDoripenem2

None≤24≥8Imipenem3≤48≥16≤24≥8Meropenem3≤48≥16≤24≥81 correspondingdiskdiffusionbreakpointsalsorevised2 Interpretivecriteriaarebasedondosageregimensof500mgevery8h

3 Interpretivecriteriaarebasedondosageregimensof1gevery8h

M100-S22.Table2B-1.Page63.New!63Pseudomonasaeruginosa

Break39提醒!

美国同时有CLSI和FDA折点CLSIandFDA建立折点的过程略有不同商业系统MUST使用FDA折点临床实验室可以使用CLSI或FDA折点认证机构接受如果是FDA-批准的商业AST系统,临床实验室使用更新的CLSI折点时，需要验证8提醒!美国同时有CLSI和FDA折点840S.typhiandExtraintestinalSalmonellaspp.andFluoroquinolones41S.typhiandExtraintestinalS41M100-S22.Table2A.Page48.S.typhiandExtraintestinalSalmonellaspp.andFluoroquinolonesNew!45M100-S22.Table2A.Page48.S.42M100-S22.Table2A.Page48.S.typhiandExtraintestinalSalmonellaspp.andCiprofloxacinNew!47M100-S22.Table2A.Page48.S.43Staphylococcusspp.-Penicillin68Staphylococcusspp.-Penicill44Inducedß-lactamaseTest苯唑西林(诱导剂)Subisolatetoagar(e.g.,BAP,MHA)Dropß-lactamdisk(e.g.,oxacillin,cefoxitin)IncubateovernightTestcellsfromperipheryofzoneIfβ-lactamasepositive(withorwithoutinduction),reportpenicillinRPosNeg71Inducedß-lactamaseTest苯唑西林Su45CloverleafAssayforβ-lactamase

S.aureus5%sheepbloodagar1unitpenicillindiskS.aureusATCC25923astheindicatorβ-lactamasenegative(penicillinS)strainSomedifficultiesreadingIsolatesA-Dareallβ-lactamasepositiveABCDβ-lactamasenegative75CloverleafAssayforβ-lactama46（22）解释标准基于每8小时一次，每次500mg的给药方案。Pseudomonasaeruginosa

Penicillins+/-β-lactamaseInhibitorsSIR商业系统MUST使用FDA折点无菌体液微生物检验的规范流程2010年后折点变化过程January2011(M100-S21)最新CLSI推荐的分枝杆菌、奴卡菌、其他需氧放线菌的药敏试验规程PK/PD(conservativelywentwith≤0.寄生虫病的临床和实验室诊断进展aeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Piperacillin-tazobactam进行药敏试验并且使用(M100version)Clinicaldatasuggestformerbreakpointstoohigh!June2010(M100-S20U)Subisolatetoagar(e.aeruginosabreakpointsoriginallysethigherthanthoseforEnterobacteriaceaebasedinpartonFDAlabelnotingthatthesedrugsshouldbeconsideredincombinationtherapywithaminoglycoside肠杆菌科–厄他培南

CLSI折点更新过程病原菌的分子进化研究进展β-lactamasepositiveβ-lactamasenegative76（22）解释标准基于每8小时一次，每次500mg的给药方案。47Staphylococcus

aureus

DiskZoneEdgeTest(10Upenicillindiskandstandarddiskdiffusionmethod)Fuzzy“beach”=β-lactamasenegativePenicillin-SSharp“cliff”=β-lactamasepositivePenicillin-RS.aureusQC:

Neg-ATCC25923Pos-ATCC29213(supplementalQC)M100-S22.Table2CSupplementalTable1.Page83.New!77Staphylococcusaureus

DiskZ48M100-S22.Table2CSupplementalTable1.Page80.β-lactamaseTests–S.aureusandS.lugdunensis80M100-S22.Table2CSupplementa49β-lactamaseTests–CoNSNOTS.lugdunensisM100-S22.Table2CSupplementalTable3.Page88.81β-lactamaseTests–CoNSNOTS50CLSIvsFDAInterpretiveCriteriaIftheregulatoryauthoritychangesbreakpoints,commercialdevicemanufacturersmayhavetoconductaclinicallaboratorytrial,submitthedatatotheregulatoryauthority,andawaitreviewandapproval.Forthesereasons,adelayofoneormoreyearsmayberequiredifaninterpretivebreakpointchangeistobeimplementedbyadevicemanufacturer.IntheUnitedStates,laboratoriesthatuseFoodandDrugAdministration(FDA)–approvedsusceptibilitytestingdevicesareallowedtouseexistingFDAinterpretivebreakpoints.EitherFDAorCLSIsusceptibilityinterpretivebreakpointsareacceptabletoclinicallaboratoryaccreditingbodies.Policiesinothercountriesmayvary.Laboratoriesshouldcheckwiththemanufacturersoftheirantimicrobialsusceptibilitytestsystemforadditionalinformationonthebreakpointsusedintheirsystem’ssoftware.CLSIvsFDAInterpretiveCrite51CLSIvsFDAFollowingdiscussionswithappropriatestakeholders,suchasinfectiousdiseasepractitionersandthepharmacydepartment,aswellasthePharmacyandTherapeuticsandInfectionControlcommitteesofthemedicalstaff,newlyapprovedorrevisedbreakpointsmaybeimplementedbyclinicallaboratories.CLSIdiskdiffusiontestbreakpointsmaybeimplementedassoonastheyarepublishedinM100.IfadeviceincludesantimicrobialtestconcentrationssufficienttoallowinterpretationofsusceptibilityandresistancetoanagentusingtheCLSIbreakpoints,alaboratorycould,afterappropriatevalidation,choosetointerpretandreportresultsusingCLSIbreakpoints.CLSIvsFDAFollowingdiscussio52革兰阴性菌耐药折点问题实用版课件53革兰阴性菌耐药折点问题实用版课件54CLSIASTStandardsforRoutineASTMIC折点-表格纸片扩散法MIC方法AllNew2012!22CLSIASTStandardsforRoutine55“感染性疾病的病原学诊断及临床应用新进展学习班”通知北京6月27-7月1日国家Ⅰ级继续教育学分10分临床微生物学检验和感染疾病诊治指导意义ISO15189与微生物检验寄生虫病的临床和实验室诊断进展真菌病的实验室诊断和新进展不明原因肺炎的临床和实验室诊断进展下呼吸道标本采集、运送和处理规范无菌体液微生物检验的规范流程临床不常见菌的培养和快速鉴定药敏试验折点建立和抗菌药物的PK/PD2012年CLSI药敏试验更新细菌耐药监测和药敏谱统计的规范方法最新CLSI推荐的分枝杆菌、奴卡菌、其他需氧放线菌的药敏试验规程病原微生物的快速分子诊断进展病原菌的分子进化研究进展实验室的生物安全、质量控制和质量保证厌氧菌和弯曲菌的培养、鉴定和药敏试验新进展微生物检验与Lis系统“感染性疾病的病原学诊断及临床应用新进展学习班”通知北京656(M100version)NewM100-S221aeruginosaMICbreakpointsarenowthesameasthoseforEnterobacteriaceae(slightdifferencesindiskdiffusionbreakpoints)(M100version)Time(hours)Pages52-60.Pseudomonasaeruginosa

Penicillins+/-β-lactamaseInhibitors(如ESBL或碳青霉烯酶)Table2B-1.Thesedosageregimencommentsarenotintendedforuseonindividualpatientreports.商业系统MUST使用FDA折点June2010(M100-S20U)2011breakpointsprimarilybasedon:Verylimitedclinicaldata(nopatientswithMICsat0.Pages52-60.真菌病的实验室诊断和新进展*目前和FDA折点相同5µg/mlMICssuggestedclinicalresponse)CeftizoximeTicarcillin-clavulanicacidVerylimitedclinicaldata(nopatientswithMICsat0.CloverleafAssayforβ-lactamase2011breakpointsprimarilybasedon:Staphylococcusspp.andFluoroquinolonesaureusQC:

Neg-ATCC25923Pages52-60.SIRThesedosageregimencommentsarenotintendedforuseonindividualpatientreports.Ceftazidime细菌耐药监测和药敏谱统计的规范方法Pseudomonasaeruginosa

Penicillins+/-β-lactamaseInhibitorsDateofRevision*Pages52-60.美罗培南MIC(µg/ml)AllNew2012!(如ESBL或碳青霉烯酶)(13)Interpretivecriteriaforimipenemandmeropenemarebasedonadosageregimenof1gevery8h.lugdunensis“Incaseswherespecificdosageregimensareimportantforproperapplicationofbreakpoints,thedosageregimenislisted.谢谢观看！(M100version)Verylimitedcli57革兰阴性菌耐药折点问题文档ppt革兰阴性菌耐药折点问题文档ppt58M100-S22PartialTableofContentsM100-S22.Page9.4M100-S22M100-S22.Page9.459更新的的总结

M100-S22.Page13.5更新的M100-S22.Page13.5602012主要变化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）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；增加多利培南折点葡萄球菌

增加金葡菌青霉素抑菌圈周边试验检测（penicillindiskzoneedgetest）β-内酰胺酶产生New!62012主要变化肠杆菌科New!661M100-S22.P222010年后折点变化过程New!7M100-S22.P222010年后折点变化过程New!762CLSIBreakpointAdditions/RevisionsSince2010AntimicrobialAgentDateofRevision*(M100version)CommentsEnterobacteriaceaeAztreonamJanuary2010(M100-S20)CefazolinJanuary2010(M100-S20)January2011(M100-S21)Breakpointswererevisedtwicesince2010CefotaximeJanuary2010(M100-S20)CeftazidimeJanuary2010(M100-S20)CeftizoximeJanuary2010(M100-S20)CeftriaxoneJanuary2010(M100-S20)DoripenemJune2010(M100-S20U)NopreviousCLSIbreakpointsfordoripenemErtapenemJune2010(M100-S20U)January2012(M100-S22)Breakpointswererevisedtwicesince2010.ImipenemJune2010(M100-S20U)MeropenemJune2010(M100-S20U)Cipro–SalmonellaonlyJanuary2012(M100-S22)CLSIBreakpointAdditions/Re63CLSIBreakpointAdditions/RevisionsSince2010AntimicrobialAgentDateofRevision*(M100version)CommentsPseudomonasaeruginosaPiperacillin-tazobactamJanuary2012(M100-S22)Ticarcillin-clavulanateJanuary2012(M100-S22)TicarcillinJanuary2012(M100-S22)PiperacillinJanuary2012(M100-S22)CLSIBreakpointAdditions/Re64肠杆菌科：

碳靑霉烯类

肠杆菌科：

碳靑霉烯类

65革兰阴性菌耐药折点问题实用版课件66美国碳靑霉烯类耐药肠杆菌科（CRE）的分布黄色：KPC酶；蓝点：IMP、VIM黄点：NDM美国碳靑霉烯类耐药肠杆菌科（CRE）的分布黄色：KPC酶；67CLSI使用以下数据建立/修订折点“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”机制与临床预后相关的MIC对于老药很少有“新”数据

药物代谢-药效学(PK-PD)分析CLSIM23-A3(2008)“体外药敏实验标准和质量控制参数的发展;批准的指南”描述了CLSI建立和修订折点的过程。CLSI使用以下数据建立/修订折点“野生菌群”或常规菌68Piperacillin-tazobactam

MICdistributionexampleBlue=wildtypeisolatesRed=isolateswithacquired“R”10Piperacillin-tazobactamMICdi69SerumConcentration(µg/ml)Time(hours)MICTimeaboveMICdosedoseCmax(peakconcentration)PK/PDGoal(“Target”)forβ-lactams=(%T>MIC)12Organism%Time>MIC肠杆菌科35%绿脓30%SerumConcentration(µg/ml)Tim70DMID2009年DMID2009年71革兰阴性菌耐药折点问题实用版课件72革兰阴性菌耐药折点问题实用版课件73Piperacillin-tazobactam6Carbapenemases(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。1 Correspondingdiskdiffusionbreakpointsalsorevised5MHTsameresultwithertapenemandmeropenem(andimipenem)disksCLSIvsFDAInterpretiveCriteriaPages52-60.*目前和FDA折点相同January2012(M100-S22)January2010(M100-S20)Pages52and56.andCiprofloxacin药敏试验折点建立和抗菌药物的PK/PDTicarcillin-clavulanicacid临床实验室可以使用CLSI或FDA折点Red=isolateswithacquired“R”mechanism3Limbago,BM.2012年CLSI绿脓杆菌折点变化Staphylococcusspp.CLSIBreakpointAdditions/RevisionsSince2010Piperacillin-tazobactam74CLSIDocumentMIC(µg/ml)DiskDiffusion(mm)SuscIntResSuscIntResM100-S20(Jan.2010)*≤24≥8≥1916-18≤15M100-S20U(June2010)≤0.250.5≥1≥2320-22≤19M100-S22(Jan2012)**≤0.51.0≥2≥2219-21≤18肠杆菌科–厄他培南

CLSI折点更新过程*目前和FDA折点相同NewNew!28CLSIDocumentMIC(µg/ml)DiskD75为何多次进行修改?2011breakpointsprimarilybasedon:MICdistributionsPK/PD(conservativelywentwith≤0.25µg/ml)Verylimitedclinicaldata(nopatientswithMICsat0.5µg/ml)2012breakpointsprimarilybasedon:AdditionalsurveillancedatashowedisolateswithMICsof0.5µg/mldidnothavecarbapenemasesFurtherreviewofPK/PDAdditionalclinicaldata(includingESBL-producingE.coliwith0.5µg/mlMICssuggestedclinicalresponse)Also,lowestertapenemconcentrationonsomecommercialpanelsis0.5µg/mlthusallowinglabstouseCLSIertapenembreakpoints(followingverification)ifbreakpointis≤0.5µg/mlbutnotif≤0.25µg/ml29为何多次进行修改?2011breakpointsprim76CLSIAgendaBookJune201130CLSIAgendaBookJune20113077CLSIAgendaBookJune201131CLSIAgendaBookJune20113178Susc.:≤0.5µg/ml/≥22mmRes.:≥2µg/ml/≤18mmVM=0.0%Ma=0.0%Mi=6.1%FORNEWBREAKPOINTSAPPROVEDJune2011Susc.:≤0.5µg/ml/≥22mmFOR79ModifiedHodgeTest(MHT)

(Table2ASupplementalTable2and3)

“NOTE:Notallcarbapenemase-producingisolatesofEnterobacteriaceaeareMHTpositiveandMHT-positiveresultsmaybeencounteredinisolateswithcarbapenemresistancemechanismsotherthancarbapenemaseproduction.”

M100-S22.Table2ASupplementalTables2and3.Pages53and57.New!36ModifiedHodgeTest(MHT)

(Ta804SelectCREExamples:CarbapenemMICs&MHT&-LactamResistanceMechanismOrganismMIC(µg/ml)1MHTResistancemechanismErtapImipMeroE.coli2>16R4R4RPos4

PlasmidampCK.pneumoniae2>16R≤0.25S8RPos5

ESBLblashvE.coli3>16R8R>16RNeg5

NDM-16K.pneumoniae32R1S2IPos5

IMP-461Interpretedwithcurrent

breakpoints2Anderson,KFetal.2009.ICAAC.D-719.3Limbago,BM.CLSIAgendabook.January2011.4MHTpositiveonlywithertapenemdisk5MHTsameresultwithertapenemandmeropenem(andimipenem)disks6Carbapenemases(metallo-lactamases)394SelectCREExamples:Carbape81进行耐药机制的初筛试验(MIC升高至接近“敏感”折点为“可疑”)进行耐药机制的特异确证试验若检测到耐药机制则更改药敏报告发现一种新型β-内酰胺酶(如ESBL或碳青霉烯酶)旧的模式ESBLMHTCourtesyofDr.JeanPatelCDC进行耐药机制的初筛试验进行耐药机制的特异确证试验若检测到耐药82新的模式进行药敏试验并且使用新的“降低的”折点以治疗为目的报告药敏结果–不更改“敏感”结果仅以感染控制和流行病学研究为目的进行特殊的耐药机制检测试验分离出肠杆菌科菌CourtesyofDr.JeanPatelCDC新的模式进行药敏试验并且使用以治疗为目的报告药敏结果仅以83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Pseudomonasaeruginosaaeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Comment(23)Page47.January2011(M100-S21)PseudomonasaeruginosaNewM100-S221typhiandExtraintestinalPiperacillin-tazobactamMICdistributionexampleaureusQC:

Neg-ATCC259235µg/mlMICssuggestedclinicalresponse)（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。Policiesinothercountriesmayvary.January2011(M100-S21)β-lactamasenegativeaureusQC:

Neg-ATCC25923IsolatesA-DareallISO15189与微生物检验3Limbago,BM.CLSIAgendabook.CLSIM100-S20-U表1A修订的碳青霉烯类药物折点和对应的药物剂量SIRSIR（22）解释标准基于每8小时一次，每次500mg的给药方案。（23）解释标准基于每天一次，每次1g的给药方案。（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。（25）解释标准基于每8小时一次，每次1g的给药方案。降低哌拉西林、哌拉西林/他唑巴坦、替卡西林、替卡西林/克拉84M100-S22.Table2ASupplementalTables2and3.Pages52-60.(旧折点)(当前折点)MHT检测碳青霉烯酶35M100-S22.(旧折点)(当前折点)MHT检测碳青霉烯85碳青霉烯类药物MIC

报告策略例#1例#2美罗培南MIC(µg/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*对常规病人的报告不必做改良霍奇试验;可以为感染控制目的而进行该试验但不要把“敏感”或“中介”改为“耐药”敏感中介耐药旧≤48≥16新≤12≥4折点(µg/ml)碳青霉烯类药物MIC

报告策略例#1例#2美罗培南M86如果用旧折点和碳青霉烯酶筛选试验阳性如果用当前折点和需要流行病学的需要进行MHT进行MHT为何做MHT?M100-S22.Comment(23)Page47.Table2ASupplementalTables2and3.Pages52and56.40如果用如果用进行MHT进行MHT为何做MHT?M100-87革兰阴性菌耐药折点问题实用版课件88绿脓杆菌57绿脓杆菌5789Pseudomonasaeruginosa

Breakpoint(MICµg/ml)RevisionsAgentOld(M100-S21)NewM100-S221SuscIntResSuscIntResPiperacillin≤64-≥128≤1632-64≥128Piperacillin-tazobactam≤64/4-≥128/4≤16/432/4-64/4≥128/4Ticarcillin≤64-≥128≤1632-64≥128Ticarcillin-clavulanate≤64/2-≥128/2≤16/232/2-64/2≥128/21 Correspondingdiskdiffusionbreakpointsalsorevised

M100-S22.Table2B-1.Page63.New!58Pseudomonasaeruginosa

Break90Pseudomonasaeruginosa

M100-S22.Table2B-1.Page63.Dosagecomments(3gevery6halsoforpiperacillinandforticarcillin)59PseudomonasaeruginosaM100-S2912012年CLSI绿脓杆菌折点变化BPiperacillin-tazobactam

2115–20

14

16/432/4–64/4

128/4(7)Interpretivecriteriaforpiperacillin(aloneorwithtazobactam)arebasedonapiperacillindosageregimenofatleast3gevery6h.OTicarcillin-clavulanicacid

2416–23

15

16/232/2–64/2

128/2(8)Interpretivecriteriaforticarcillin(aloneorwithclavulanate)arebasedonaticarcillindosageregimenofatleast3gevery6h.BDoripenem

1916–18

15

24

8(12)Interpretivecriteriafordoripenemarebasedonadosageregimenof500mgevery8h.BImipenem/Meropenem

1916–18

15

24

8(13)Interpretivecriteriaforimipenemandmeropenemarebasedonadosageregimenof1gevery8h.2012年CLSI绿脓杆菌折点变化BPiperacilli92SectionIII. Therapy-RelatedComments

“Incaseswherespecificdosageregimensareimportantforproperapplicationofbreakpoints,thedosageregimenislisted.Thesedosageregimencommentsarenotintendedforuseonindividualpatientreports.”M100-S22.Instructions.Page28.New!60SectionIII. Therapy-RelatedC93最新CLSI推荐的分枝杆菌、奴卡菌、其他需氧放线菌的药敏试验规程AntimicrobialAgentβ-lactamasepositive临床实验室可以使用CLSI或FDA折点ISO15189与微生物检验SerumConcentration(µg/ml)DosagecommentsSIR增加金葡菌青霉素抑菌圈周边试验检测（penicillindiskzoneedgetest）β-内酰胺酶产生Ticarcillin-clavulanateJanuary2010(M100-S20)CLSIAgendaBookJune2011CLSIBreakpointAdditions/RevisionsSince2010Enterobacteriaceae进行耐药机制的初筛试验Therapy-RelatedComments*目前和FDA折点相同Pages53and57.January2012(M100-S22)Salmonellaspp.Pseudomonasaeruginosa

Penicillins+/-β-lactamaseInhibitors

P.aeruginosabreakpointsoriginallysethigherthanthoseforEnterobacteriaceaebasedinpartonFDAlabelnotingthatthesedrugsshouldbeconsideredincombinationtherapywithaminoglycosideDeletedcommentfromTable2B-1-“Rx:Thesusceptiblecategoryforpenicillins,β-lactam/β-lactamaseinhibitorsimpliestheneedforhigh-dosetherapyforseriousinfectionscausedbyP.aeruginosa.Fortheseinfections,monotherapyhasbeenassociatedwithclinicalfailure”P.aeruginosaMICbreakpointsarenowthesameasthoseforEnterobacteriaceae(slightdifferencesindiskdiffusionbreakpoints)61最新CLSI推荐的分枝杆菌、奴卡菌、其他需氧放线菌的药敏试验94Outcomesofbacteremia(N=34episodes)duetoP.aeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Tametal.2008.Cli