《革蘭陰性菌耐藥折點問題》

CLSIASTStandards

January2012M100-S22Tables(2012)*M02-A11DiskDiffusionMethod(2012)**M07-A9MICMethod(2012)**M11-A7AnaerobeMICTesting(2007)New!3現(xiàn)在是1頁\一共有56頁\編輯于星期四M100-S22PartialTableofContentsM100-S22.Page9.4現(xiàn)在是2頁\一共有56頁\編輯于星期四更新的的總結(jié)

M100-S22.Page13.5現(xiàn)在是3頁\一共有56頁\編輯于星期四2012主要變化腸桿菌科修訂厄他培南折點增加環(huán)丙沙星折點（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/克拉維酸折點降低亞胺培南、美羅培南折點；增加多利培南折點葡萄球菌

增加金葡菌青霉素抑菌圈周邊試驗檢測（penicillindiskzoneedgetest）β-內(nèi)酰胺酶產(chǎn)生New!6現(xiàn)在是4頁\一共有56頁\編輯于星期四M100-S22.P222010年后折點變化過程New!7現(xiàn)在是5頁\一共有56頁\編輯于星期四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)現(xiàn)在是6頁\一共有56頁\編輯于星期四CLSIBreakpointAdditions/RevisionsSince2010AntimicrobialAgentDateofRevision*(M100version)CommentsPseudomonasaeruginosaPiperacillin-tazobactamJanuary2012(M100-S22)Ticarcillin-clavulanateJanuary2012(M100-S22)TicarcillinJanuary2012(M100-S22)PiperacillinJanuary2012(M100-S22)現(xiàn)在是7頁\一共有56頁\編輯于星期四腸桿菌科：

碳靑霉烯類

現(xiàn)在是8頁\一共有56頁\編輯于星期四現(xiàn)在是9頁\一共有56頁\編輯于星期四美國碳靑霉烯類耐藥腸桿菌科（CRE）的分布黃色：KPC酶；藍(lán)點：IMP、VIM黃點：NDM現(xiàn)在是10頁\一共有56頁\編輯于星期四CLSI使用以下數(shù)據(jù)建立/修訂折點“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”機制與臨床預(yù)后相關(guān)的MIC對于老藥很少有“新”數(shù)據(jù)

藥物代謝-藥效學(xué)(PK-PD)分析CLSIM23-A3(2008)“體外藥敏實驗標(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建立和修訂折點的過程?，F(xiàn)在是11頁\一共有56頁\編輯于星期四Piperacillin-tazobactam

MICdistributionexampleBlue=wildtype

isolatesRed=isolateswithacquired“R”10現(xiàn)在是12頁\一共有56頁\編輯于星期四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%現(xiàn)在是13頁\一共有56頁\編輯于星期四DMID2009年現(xiàn)在是14頁\一共有56頁\編輯于星期四現(xiàn)在是15頁\一共有56頁\編輯于星期四現(xiàn)在是16頁\一共有56頁\編輯于星期四現(xiàn)在是17頁\一共有56頁\編輯于星期四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折點更新過程*目前和FDA折點相同NewNew!28現(xiàn)在是18頁\一共有56頁\編輯于星期四為何多次進(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現(xiàn)在是19頁\一共有56頁\編輯于星期四CLSIAgendaBookJune201130現(xiàn)在是20頁\一共有56頁\編輯于星期四CLSIAgendaBookJune201131現(xiàn)在是21頁\一共有56頁\編輯于星期四Susc.:≤0.5μg/ml/≥22mmRes.:≥2μg/ml/≤18mmVM=0.0%Ma=0.0%Mi=6.1%FORNEWBREAKPOINTSAPPROVEDJune2011現(xiàn)在是22頁\一共有56頁\編輯于星期四ModifiedHodgeTest(MHT)

(Table2ASupplementalTable2and3)

“NOTE:Notallcarbapenemase-producingisolatesofEnterobacteriaceaeareMHTpositiveandMHT-positiveresultsmaybeencounteredinisolateswithcarbapenemresistancemechanismsotherthancarbapenemaseproduction.”

M100-S22.Table2ASupplementalTables2and3.Pages53and57.New!36現(xiàn)在是23頁\一共有56頁\編輯于星期四4SelectCREExamples: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現(xiàn)在是24頁\一共有56頁\編輯于星期四進(jìn)行耐藥機制的初篩試驗

(MIC升高至接近“敏感”折點為

“可疑”)進(jìn)行耐藥機制的特異確證試驗若檢測到耐藥機制則更改藥敏報告發(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現(xiàn)在是25頁\一共有56頁\編輯于星期四新的模式進(jìn)行藥敏試驗并且使用

新的“降低的”折點以治療為目的報告藥敏結(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)行特殊的耐藥機制檢測試驗分離出腸桿菌科菌CourtesyofDr.JeanPatelCDC現(xiàn)在是26頁\一共有56頁\編輯于星期四CLSIM100-S20-U表1A修訂的碳青霉烯類藥物折點和對應(yīng)的藥物劑量SIRSIR（22）解釋標(biāo)準(zhǔn)基于每8小時一次，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小時一次，每次500mg或每8小時一次，每次1g的給藥方案。（25）解釋標(biāo)準(zhǔn)基于每8小時一次，每次1g的給藥方案。現(xiàn)在是27頁\一共有56頁\編輯于星期四M100-S22.Table2ASupplementalTables2and3.Pages52-60.(舊折點)(當(dāng)前折點)MHT檢測碳青霉烯酶35現(xiàn)在是28頁\一共有56頁\編輯于星期四碳青霉烯類藥物MIC

報告策略例#1例#2美羅培南MIC(μg/ml)4422改良霍奇試驗*陽性陰性陽性陰性報告(舊折點)耐藥敏感耐藥敏感報告(新折點)*耐藥耐藥中介中介*對常規(guī)病人的報告不必做改良霍奇試驗;可以為感染控制目的而進(jìn)行該試驗但不要把“敏感”或“中介”改為“耐藥”敏感中介耐藥舊≤48≥16新≤12≥4折點(μg/ml)現(xiàn)在是29頁\一共有56頁\編輯于星期四如果用

舊折點和碳青霉烯酶篩選試驗陽性如果用當(dāng)前折點和

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現(xiàn)在是30頁\一共有56頁\編輯于星期四現(xiàn)在是31頁\一共有56頁\編輯于星期四綠膿桿菌57現(xiàn)在是32頁\一共有56頁\編輯于星期四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現(xiàn)在是33頁\一共有56頁\編輯于星期四Pseudomonasaeruginosa

M100-S22.Table2B-1.Page63.Dosagecomments(3gevery6halsoforpiperacillinandforticarcillin)59現(xiàn)在是34頁\一共有56頁\編輯于星期四2012年CLSI綠膿桿菌折點變化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.現(xiàn)在是35頁\一共有56頁\編輯于星期四SectionIII. Therapy-RelatedComments

“Incaseswherespecificdosageregimensareimportantforproperapplicationofbreakpoints,thedosageregimenislisted.Thesedosageregimencommentsarenotintendedforuseonindividualpatientreports.”M100-S22.Instructions.Page28.New!60現(xiàn)在是36頁\一共有56頁\編輯于星期四Pseudomonasaeruginosa

Penicillins+/-β-lactamaseInhibitors

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

Enterobacteriaceae(slightdifferencesindiskdiffusionbreakpoints)61現(xiàn)在是37頁\一共有56頁\編輯于星期四Outcomesofbacteremia(N=34episodes)duetoP.aeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Tametal.2008.ClinInfectDis.46:862.22.2%85.7%30.0%20.5%Clinicaldatasuggestformerbreakpointstoohigh!62現(xiàn)在是38頁\一共有56頁\編輯于星期四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現(xiàn)在是39頁\一共有56頁\編輯于星期四提醒!

美國同時有CLSI和FDA折點CLSIandFDA建立折點的過程略有不同商業(yè)系統(tǒng)

MUST使用FDA折點臨床實驗室可以使用

CLSI或FDA折點認(rèn)證機構(gòu)接受如果是FDA-批準(zhǔn)的商業(yè)AST系統(tǒng),臨床實驗室使用更新的CLSI折點時，需要驗證8現(xiàn)在是40頁\一共有56頁\編輯于星期四S.typhiandExtraintestinalSalmonellaspp.andFluoroquinolones41現(xiàn)在是41頁\一共有56頁\編輯于星期四M100-S22.Table2A.Page48.S.typhiandExtraintestinalSalmonellaspp.andFluoroquinolonesNew!45現(xiàn)在是42頁\一共有56頁\編輯于星期四M100-S22.Table2A.Page48.S.typhiandExtraintestinalSalmonellaspp.andCiprofloxacinNew!47現(xiàn)在是43頁\一共有56頁\編輯于星期四Staphylococcusspp.-Penicillin68現(xiàn)在是44頁\一共有56頁\編輯于星期四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現(xiàn)在是45頁\一共有56頁\編輯于星期四CloverleafAssayforβ-lactamase

S.aureus5%sheepbloodagar1unitpenicillindiskS.aureusATCC25923astheindicatorβ-lactamasenegative(penicillinS)strainSomedifficultiesreadingIsolatesA-Dareallβ-lactamasepositiveABCDβ-lactamasenegative75現(xiàn)在是46頁\一共有56頁\編輯于星期四β-lactamasepositiveβ-lactamasenegative76現(xiàn)在是47頁\一共有56頁\編輯于星期四Staphylococcus

aureus

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

Neg-ATCC25923Pos-ATCC29213(supplementalQC)M100-S22.Table2CSupplementalTable1.Page83.New!77現(xiàn)在是48頁\一共有56頁\編輯于星期四M100-S22.Table2CSupplementalTable1.Page80.β-lactamaseTests–S.aureusandS.lugdunensis80現(xiàn)在是49頁\一共有56頁\編輯于星期四β-lactamaseTests–CoNSNOTS.lugdunensisM100-S22.Table2CSupplementalTable3.Page88.81現(xiàn)在是50頁\一共有56頁\編輯于星期四CLSIvsFDAInterpretiveCriteriaIftheregulatoryauthoritychangesbreakpoints,commercialdevicemanufacturersmayhavetoconductaclinicallaboratorytrial,submitthedatatotheregulatoryauthority,andawaitreviewandapproval.Forthesereasons,adelayofoneormoreyearsmayberequiredifaninterpretivebreakpointchangeistobeimplementedbyadevicemanufacturer.IntheUnitedStates,laboratoriesthatuseFoodandDrugAdministration(FDA)–approvedsusceptibilitytestingdevicesareallowedtouseexistingFDAinterpretivebreakpoints.EitherFDAorCLSIsusceptibilityinterpretivebreakpointsareacceptabletoclinicallaboratoryaccreditingbodies.Policiesinothercountriesmayvary.Laboratoriesshouldcheckwiththemanufacturersoftheirantimicrobialsusceptibilitytestsystemforadditionalinformationonthe