《革蘭陰性菌耐藥折點(diǎn)問題》

CLSIASTStandards

January2012M100-S22Tables(2012)*M02-A11DiskDiffusionMethod(2012)**M07-A9MICMethod(2012)**M11-A7AnaerobeMICTesting(2007)New!3本文檔共56頁(yè)；當(dāng)前第1頁(yè)；編輯于星期三\0點(diǎn)2分M100-S22PartialTableofContentsM100-S22.Page9.4本文檔共56頁(yè)；當(dāng)前第2頁(yè)；編輯于星期三\0點(diǎn)2分更新的的總結(jié)

M100-S22.Page13.5本文檔共56頁(yè)；當(dāng)前第3頁(yè)；編輯于星期三\0點(diǎn)2分2012主要變化腸桿菌科修訂厄他培南折點(diǎn)增加環(huán)丙沙星折點(diǎn)（傷寒沙門菌和胃腸外沙門菌）綠膿桿菌降低哌拉西林、哌拉西林/他唑巴坦、替卡西林、替卡西林/克拉維酸折點(diǎn)降低亞胺培南、美羅培南折點(diǎn)；增加多利培南折點(diǎn)葡萄球菌

增加金葡菌青霉素抑菌圈周邊試驗(yàn)檢測(cè)（penicillindiskzoneedgetest）β-內(nèi)酰胺酶產(chǎn)生New!6本文檔共56頁(yè)；當(dāng)前第4頁(yè)；編輯于星期三\0點(diǎn)2分M100-S22.P222010年后折點(diǎn)變化過程N(yùn)ew!7本文檔共56頁(yè)；當(dāng)前第5頁(yè)；編輯于星期三\0點(diǎn)2分CLSIBreakpointAdditions/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)本文檔共56頁(yè)；當(dāng)前第6頁(yè)；編輯于星期三\0點(diǎn)2分CLSIBreakpointAdditions/RevisionsSince2010AntimicrobialAgentDateofRevision*(M100version)CommentsPseudomonasaeruginosaPiperacillin-tazobactamJanuary2012(M100-S22)Ticarcillin-clavulanateJanuary2012(M100-S22)TicarcillinJanuary2012(M100-S22)PiperacillinJanuary2012(M100-S22)本文檔共56頁(yè)；當(dāng)前第7頁(yè)；編輯于星期三\0點(diǎn)2分腸桿菌科：

碳靑霉烯類

本文檔共56頁(yè)；當(dāng)前第8頁(yè)；編輯于星期三\0點(diǎn)2分本文檔共56頁(yè)；當(dāng)前第9頁(yè)；編輯于星期三\0點(diǎn)2分美國(guó)碳靑霉烯類耐藥腸桿菌科（CRE）的分布黃色：KPC酶；藍(lán)點(diǎn)：IMP、VIM黃點(diǎn)：NDM本文檔共56頁(yè)；當(dāng)前第10頁(yè)；編輯于星期三\0點(diǎn)2分CLSI使用以下數(shù)據(jù)建立/修訂折點(diǎn)“野生菌群”或常規(guī)菌群的MIC分布野生菌群=未攜帶獲得性“耐藥”機(jī)制與臨床預(yù)后相關(guān)的MIC對(duì)于老藥很少有“新”數(shù)據(jù)

藥物代謝-藥效學(xué)(PK-PD)分析CLSIM23-A3(2008)“體外藥敏實(shí)驗(yàn)標(biāo)準(zhǔn)和質(zhì)量控制參數(shù)的發(fā)展;批準(zhǔn)的指南”描述了CLSI建立和修訂折點(diǎn)的過程。本文檔共56頁(yè)；當(dāng)前第11頁(yè)；編輯于星期三\0點(diǎn)2分Piperacillin-tazobactam

MICdistributionexampleBlue=wildtype

isolatesRed=isolateswithacquired“R”mechanism10本文檔共56頁(yè)；當(dāng)前第12頁(yè)；編輯于星期三\0點(diǎn)2分SerumConcentration(μg/ml)Time(hours)MICTimeaboveMICdosedoseCmax(peakconcentration)PK/PDGoal(“Target”)forβ-lactams=(%T>MIC)12Organism%Time>MIC腸桿菌科35%綠膿30%本文檔共56頁(yè)；當(dāng)前第13頁(yè)；編輯于星期三\0點(diǎn)2分DMID2009年本文檔共56頁(yè)；當(dāng)前第14頁(yè)；編輯于星期三\0點(diǎn)2分本文檔共56頁(yè)；當(dāng)前第15頁(yè)；編輯于星期三\0點(diǎn)2分本文檔共56頁(yè)；當(dāng)前第16頁(yè)；編輯于星期三\0點(diǎn)2分本文檔共56頁(yè)；當(dāng)前第17頁(yè)；編輯于星期三\0點(diǎn)2分CLSIDocumentMIC(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腸桿菌科–厄他培南

CLSI折點(diǎn)更新過程*目前和FDA折點(diǎn)相同NewNew!28本文檔共56頁(yè)；當(dāng)前第18頁(yè)；編輯于星期三\0點(diǎn)2分為何多次進(jìn)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本文檔共56頁(yè)；當(dāng)前第19頁(yè)；編輯于星期三\0點(diǎn)2分CLSIAgendaBookJune201130本文檔共56頁(yè)；當(dāng)前第20頁(yè)；編輯于星期三\0點(diǎn)2分CLSIAgendaBookJune201131本文檔共56頁(yè)；當(dāng)前第21頁(yè)；編輯于星期三\0點(diǎn)2分Susc.:≤0.5μg/ml/≥22mmRes.:≥2μg/ml/≤18mmVM=0.0%Ma=0.0%Mi=6.1%FORNEWBREAKPOINTSAPPROVEDJune2011本文檔共56頁(yè)；當(dāng)前第22頁(yè)；編輯于星期三\0點(diǎn)2分ModifiedHodgeTest(MHT)

(Table2ASupplementalTable2and3)

“NOTE:Notallcarbapenemase-producingisolatesofEnterobacteriaceaeareMHTpositiveandMHT-positiveresultsmaybeencounteredinisolateswithcarbapenemresistancemechanismsotherthancarbapenemaseproduction.”

M100-S22.Table2ASupplementalTables2and3.Pages53and57.New!36本文檔共56頁(yè)；當(dāng)前第23頁(yè)；編輯于星期三\0點(diǎn)2分4SelectCREExamples: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)39本文檔共56頁(yè)；當(dāng)前第24頁(yè)；編輯于星期三\0點(diǎn)2分進(jìn)行耐藥機(jī)制的初篩試驗(yàn)

(MIC升高至接近“敏感”折點(diǎn)為

“可疑”)進(jìn)行耐藥機(jī)制的特異確證試驗(yàn)若檢測(cè)到耐藥機(jī)制則更改藥敏報(bào)告發(fā)現(xiàn)一種新型β-內(nèi)酰胺酶(如ESBL或碳青霉烯酶)舊的模式ESBLMHTCourtesyofDr.JeanPatelCDC本文檔共56頁(yè)；當(dāng)前第25頁(yè)；編輯于星期三\0點(diǎn)2分新的模式進(jìn)行藥敏試驗(yàn)并且使用

新的“降低的”折點(diǎn)以治療為目的報(bào)告藥敏結(jié)果–不更改“敏感”結(jié)果僅以感染控制和流行病學(xué)研究為目的進(jìn)行特殊的耐藥機(jī)制檢測(cè)試驗(yàn)分離出腸桿菌科菌CourtesyofDr.JeanPatelCDC本文檔共56頁(yè)；當(dāng)前第26頁(yè)；編輯于星期三\0點(diǎn)2分CLSIM100-S20-U表1A修訂的碳青霉烯類藥物折點(diǎn)和對(duì)應(yīng)的藥物劑量SIRSIR（22）解釋標(biāo)準(zhǔn)基于每8小時(shí)一次，每次500mg的給藥方案。（23）解釋標(biāo)準(zhǔn)基于每天一次，每次1g的給藥方案。（24）解釋標(biāo)準(zhǔn)基于每6小時(shí)一次，每次500mg或每8小時(shí)一次，每次1g的給藥方案。（25）解釋標(biāo)準(zhǔn)基于每8小時(shí)一次，每次1g的給藥方案。本文檔共56頁(yè)；當(dāng)前第27頁(yè)；編輯于星期三\0點(diǎn)2分M100-S22.Table2ASupplementalTables2and3.Pages52-60.(舊折點(diǎn))(當(dāng)前折點(diǎn))MHT檢測(cè)碳青霉烯酶35本文檔共56頁(yè)；當(dāng)前第28頁(yè)；編輯于星期三\0點(diǎn)2分碳青霉烯類藥物MIC

報(bào)告策略例#1例#2美羅培南MIC(μg/ml)4422改良霍奇試驗(yàn)*陽(yáng)性陰性陽(yáng)性陰性報(bào)告(舊折點(diǎn))耐藥敏感耐藥敏感報(bào)告(新折點(diǎn))*耐藥耐藥中介中介*對(duì)常規(guī)病人的報(bào)告不必做改良霍奇試驗(yàn);可以為感染控制目的而進(jìn)行該試驗(yàn)但不要把“敏感”或“中介”改為“耐藥”敏感中介耐藥舊≤48≥16新≤12≥4折點(diǎn)(μg/ml)本文檔共56頁(yè)；當(dāng)前第29頁(yè)；編輯于星期三\0點(diǎn)2分如果用

舊折點(diǎn)和碳青霉烯酶篩選試驗(yàn)陽(yáng)性如果用當(dāng)前折點(diǎn)和

需要流行病學(xué)的需要進(jìn)行MHT進(jìn)行MHT為何做MHT?M100-S22.Comment(23)Page47.Table2ASupplementalTables2and3.Pages52and56.40本文檔共56頁(yè)；當(dāng)前第30頁(yè)；編輯于星期三\0點(diǎn)2分本文檔共56頁(yè)；當(dāng)前第31頁(yè)；編輯于星期三\0點(diǎn)2分綠膿桿菌57本文檔共56頁(yè)；當(dāng)前第32頁(yè)；編輯于星期三\0點(diǎn)2分Pseudomonasaeruginosa

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!58本文檔共56頁(yè)；當(dāng)前第33頁(yè)；編輯于星期三\0點(diǎn)2分Pseudomonasaeruginosa

M100-S22.Table2B-1.Page63.Dosagecomments(3gevery6halsoforpiperacillinandforticarcillin)59本文檔共56頁(yè)；當(dāng)前第34頁(yè)；編輯于星期三\0點(diǎn)2分2012年CLSI綠膿桿菌折點(diǎn)變化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.本文檔共56頁(yè)；當(dāng)前第35頁(yè)；編輯于星期三\0點(diǎn)2分SectionIII. Therapy-RelatedComments

“Incaseswherespecificdosageregimensareimportantforproperapplicationofbreakpoints,thedosageregimenislisted.Thesedosageregimencommentsarenotintendedforuseonindividualpatientreports.”M100-S22.Instructions.Page28.New!60本文檔共56頁(yè)；當(dāng)前第36頁(yè)；編輯于星期三\0點(diǎn)2分Pseudomonasaeruginosa

Penicillins+/-β-lactamaseInhibitors

P.aeruginosabreakpointsoriginallysethigherthanthoseforEnterobacteriaceaebasedinpartonFDAlabelnotingthatthesedrugsshouldbeconsideredincombinationtherapywithaminoglycosideDeletedcommentfromTable2B-1-“Rx:Thesusceptiblecategoryforpenicillins,β-lactam/β-lactamaseinhibitorsimpliestheneedforhigh-dosetherapyforseriousinfectionscausedbyP.aeruginosa.Fortheseinfections,monotherapyhasbeenassociatedwithclinicalfailure”P.aeruginosaMICbreakpointsarenowthesameasthosefor

Enterobacteriaceae(slightdifferencesindiskdiffusionbreakpoints)61本文檔共56頁(yè)；當(dāng)前第37頁(yè)；編輯于星期三\0點(diǎn)2分Outcomesofbacteremia(N=34episodes)duetoP.aeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Tametal.2008.ClinInfectDis.46:862.22.2%85.7%30.0%20.5%Clinicaldatasuggestformerbreakpointstoohigh!62本文檔共56頁(yè)；當(dāng)前第38頁(yè)；編輯于星期三\0點(diǎn)2分Pseudomonasaeruginosa

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!63本文檔共56頁(yè)；當(dāng)前第39頁(yè)；編輯于星期三\0點(diǎn)2分提醒!

美國(guó)同時(shí)有CLSI和FDA折點(diǎn)CLSIandFDA建立折點(diǎn)的過程略有不同商業(yè)系統(tǒng)

MUST使用FDA折點(diǎn)臨床實(shí)驗(yàn)室可以使用

CLSI或FDA折點(diǎn)認(rèn)證機(jī)構(gòu)接受如果是FDA-批準(zhǔn)的商業(yè)AST系統(tǒng),臨床實(shí)驗(yàn)室使用更新的CLSI折點(diǎn)時(shí)，需要驗(yàn)證8本文檔共56頁(yè)；當(dāng)前第40頁(yè)；編輯于星期三\0點(diǎn)2分S.typhiandExtraintestinalSalmonellaspp.andFluoroquinolones41本文檔共56頁(yè)；當(dāng)前第41頁(yè)；編輯于星期三\0點(diǎn)2分M100-S22.Table2A.Page48.S.typhiandExtraintestinalSalmonellaspp.andFluoroquinolonesNew!45本文檔共56頁(yè)；當(dāng)前第42頁(yè)；編輯于星期三\0點(diǎn)2分M100-S22.Table2A.Page48.S.typhiandExtraintestinalSalmonellaspp.andCiprofloxacinNew!47本文檔共56頁(yè)；當(dāng)前第43頁(yè)；編輯于星期三\0點(diǎn)2分Staphylococcusspp.-Penicillin68本文檔共56頁(yè)；當(dāng)前第44頁(yè)；編輯于星期三\0點(diǎn)2分Induced?-lactamaseTest苯唑西林(誘導(dǎo)劑)Subisolatetoagar(e.g.,BAP,MHA)Drop?-lactamdisk(e.g.,oxacillin,cefoxitin)IncubateovernightTestcellsfromperipheryofzoneIfβ-lactamasepositive(withorwithoutinduction),reportpenicillinRPosNeg71本文檔共56頁(yè)；當(dāng)前第45頁(yè)；編輯于星期三\0點(diǎn)2分CloverleafAssayforβ-lactamase

S.aureus5%sheepbloodagar1unitpenicillindiskS.aureusATCC25923astheindicatorβ-lactamasenegative(penicillinS)strainSomedifficultiesreadingIsolatesA-Dareallβ-lactamasepositiveABCDβ-lactamasenegative75本文檔共56頁(yè)；當(dāng)前第46頁(yè)；編輯于星期三\0點(diǎn)2分β-lactamasepositiveβ-lactamasenegative76本文檔共56頁(yè)；當(dāng)前第47頁(yè)；編輯于星期三\0點(diǎn)2分Staphylococcus

aureus

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

Neg-ATCC25923Pos-ATCC29213(supplementalQC)M100-S22.Table2CSupplementalTable1.Page83.New!77本文檔共56頁(yè)；當(dāng)前第48頁(yè)；編輯于星期三\0點(diǎn)2分M100-S22.Table2CSupplementalTable1.Page80.β-lactamaseTests–S.aureusandS.lugdunensis80本文檔共56頁(yè)；當(dāng)前第49頁(yè)；編輯于星期三\0點(diǎn)2分β-lactamaseTests–CoNSNOTS.lugdunensisM100-S22.Table2CSupplementalTable3.Page88.81本文檔共56頁(yè)；當(dāng)前第50頁(yè)；編輯于星期三\0點(diǎn)2分CLSIvsFDAInterpretiveCriteriaIftheregulatoryauthoritychangesbreakpoints,commercialdevicemanufacturersmayhavetoconductaclinicallaboratorytrial,submitthedatatotheregulatoryauthority,andawaitreviewandapproval.Forthesereasons,adelayofoneormoreyearsmayberequiredifaninterpretivebreakpointchangeistobeimplementedbyadevicemanufacturer.IntheUnitedStates,laboratoriesthatuseFoodandDrugAdministration(FDA)–approvedsusceptibilitytestingdevicesareallowedtouseexistingFDAinterpretivebreakpoints.EitherFDAorCLSIsusceptibilityinterpretivebreakpointsareacceptabletoclinicallaboratoryaccreditingbodies.Policiesinothercountriesmayvary.Laboratoriesshouldcheckwiththemanufacturersoftheirantimicrobialsusceptibilitytestsystemforadditionalinformationonthebre