革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件

革蘭陰性菌耐藥折點(diǎn)問題文檔ppt革蘭陰性菌耐藥折點(diǎn)問題文檔ppt1M100-S22PartialTableofContentsM100-S22.Page9.4M100-S22M100-S22.Page9.42更新的的總結(jié)

M100-S22.Page13.5更新的M100-S22.Page13.532012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!62012主要變化腸桿菌科New!64M100-S22.P222010年后折點(diǎn)變化過程N(yùn)ew!7M100-S22.P222010年后折點(diǎn)變化過程N(yùn)ew!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腸桿菌科：

碳靑霉烯類

腸桿菌科：

碳靑霉烯類

8革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件9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美國(guó)碳靑霉烯類耐藥腸桿菌科（CRE）的分布黃色：KPC酶；10CLSI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。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11Piperacillin-tazobactam

MICdistributionexampleBlue=wildtypeisolatesRed=isolateswithacquired“R”10Piperacillin-tazobactamMICdi12SerumConcentration(μg/ml)Time(hours)MICTimeaboveMICdosedoseCmax(peakconcentration)PK/PDGoal(“Target”)forβ-lactams=(%T>MIC)12Organism%Time>MIC腸桿菌科35%綠膿30%SerumConcentration(μg/ml)Tim13DMID2009年DMID2009年14革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件15革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件16Piperacillin-tazobactam6Carbapenemases(metallo-lactamases)（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。1 Correspondingdiskdiffusionbreakpointsalsorevised5MHTsameresultwithertapenemandmeropenem(andimipenem)disksCLSIvsFDAInterpretiveCriteriaPages52-60.*目前和FDA折點(diǎn)相同January2012(M100-S22)January2010(M100-S20)Pages52and56.andCiprofloxacin藥敏試驗(yàn)折點(diǎn)建立和抗菌藥物的PK/PDTicarcillin-clavulanicacid臨床實(shí)驗(yàn)室可以使用CLSI或FDA折點(diǎn)Red=isolateswithacquired“R”mechanism3Limbago,BM.2012年CLSI綠膿桿菌折點(diǎn)變化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!28CLSIDocumentMIC(μg/ml)DiskD18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為何多次進(jìn)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進(jìn)行耐藥機(jī)制的初篩試驗(yàn)進(jìn)行耐藥機(jī)制的特異確證試驗(yàn)若檢測(cè)到耐藥25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新的模式進(jìn)行藥敏試驗(yàn)并且使用以治療為目的報(bào)告藥敏結(jié)果僅以26降低哌拉西林、哌拉西林/他唑巴坦、替卡西林、替卡西林/克拉維酸折點(diǎn)Pseudomonasaeruginosaaeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Comment(23)Page47.January2011(M100-S21)PseudomonasaeruginosaNewM100-S221typhiandExtraintestinalPiperacillin-tazobactamMICdistributionexampleaureusQC:

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

Neg-ATCC25923IsolatesA-DareallISO15189與微生物檢驗(yàn)3Limbago,BM.CLSIAgendabook.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。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.(舊折點(diǎn))(當(dāng)前折點(diǎn))MHT檢測(cè)碳青霉烯酶35M100-S22.(舊折點(diǎn))(當(dāng)前折點(diǎn))MHT檢測(cè)碳青霉烯28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)*陽性陰性陽性陰性報(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)碳青霉烯類藥物MIC

報(bào)告策略例#1例#2美羅培南M29如果用舊折點(diǎn)和碳青霉烯酶篩選試驗(yàn)陽性如果用當(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如果用如果用進(jìn)行MHT進(jìn)行MHT為何做MHT?M100-30革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件31綠膿桿菌57綠膿桿菌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.2012年CLSI綠膿桿菌折點(diǎn)變化BPiperacilli35SectionIII. Therapy-RelatedComments

“Incaseswherespecificdosageregimensareimportantforproperapplicationofbreakpoints,thedosageregimenislisted.Thesedosageregimencommentsarenotintendedforuseonindividualpatientreports.”M100-S22.Instructions.Page28.New!60SectionIII. Therapy-RelatedC36最新CLSI推薦的分枝桿菌、奴卡菌、其他需氧放線菌的藥敏試驗(yàn)規(guī)程AntimicrobialAgentβ-lactamasepositive臨床實(shí)驗(yàn)室可以使用CLSI或FDA折點(diǎn)ISO15189與微生物檢驗(yàn)SerumConcentration(μg/ml)DosagecommentsSIR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Ticarcillin-clavulanateJanuary2010(M100-S20)CLSIAgendaBookJune2011CLSIBreakpointAdditions/RevisionsSince2010Enterobacteriaceae進(jìn)行耐藥機(jī)制的初篩試驗(yàn)Therapy-RelatedComments*目前和FDA折點(diǎn)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推薦的分枝桿菌、奴卡菌、其他需氧放線菌的藥敏試驗(yàn)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提醒!美國(guó)同時(shí)有CLSI和FDA折點(diǎn)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.-Penicill44Induced?-lactamaseTest苯唑西林(誘導(dǎo)劑)Subisolatetoagar(e.g.,BAP,MHA)Drop?-lactamdisk(e.g.,oxacillin,cefoxitin)IncubateovernightTestcellsfromperipheryofzoneIfβ-lactamasepositive(withorwithoutinduction),reportpenicillinRPosNeg71Induced?-lactamaseTest苯唑西林Su45CloverleafAssayforβ-lactamase

S.aureus5%sheepbloodagar1unitpenicillindiskS.aureusATCC25923astheindicatorβ-lactamasenegative(penicillinS)strainSomedifficultiesreadingIsolatesA-Dareallβ-lactamasepositiveABCDβ-lactamasenegative75CloverleafAssayforβ-lactama46（22）解釋標(biāo)準(zhǔn)基于每8小時(shí)一次，每次500mg的給藥方案。Pseudomonasaeruginosa

Penicillins+/-β-lactamaseInhibitorsSIR商業(yè)系統(tǒng)MUST使用FDA折點(diǎn)無菌體液微生物檢驗(yàn)的規(guī)范流程2010年后折點(diǎn)變化過程January2011(M100-S21)最新CLSI推薦的分枝桿菌、奴卡菌、其他需氧放線菌的藥敏試驗(yàn)規(guī)程PK/PD(conservativelywentwith≤0.寄生蟲病的臨床和實(shí)驗(yàn)室診斷進(jìn)展aeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Piperacillin-tazobactam進(jìn)行藥敏試驗(yàn)并且使用(M100version)Clinicaldatasuggestformerbreakpointstoohigh!June2010(M100-S20U)Subisolatetoagar(e.aeruginosabreakpointsoriginallysethigherthanthoseforEnterobacteriaceaebasedinpartonFDAlabelnotingthatthesedrugsshouldbeconsideredincombinationtherapywithaminoglycoside腸桿菌科–厄他培南

CLSI折點(diǎn)更新過程病原菌的分子進(jìn)化研究進(jìn)展β-lactamasepositiveβ-lactamasenegative76（22）解釋標(biāo)準(zhǔn)基于每8小時(shí)一次，每次500mg的給藥方案。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革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件53革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件54CLSIASTStandardsforRoutineASTMIC折點(diǎn)-表格紙片擴(kuò)散法MIC方法AllNew2012!22CLSIASTStandardsforRoutine55“感染性疾病的病原學(xué)診斷及臨床應(yīng)用新進(jìn)展學(xué)習(xí)班”通知北京6月27-7月1日國(guó)家Ⅰ級(jí)繼續(xù)教育學(xué)分10分臨床微生物學(xué)檢驗(yàn)和感染疾病診治指導(dǎo)意義ISO15189與微生物檢驗(yàn)寄生蟲病的臨床和實(shí)驗(yàn)室診斷進(jìn)展真菌病的實(shí)驗(yàn)室診斷和新進(jìn)展不明原因肺炎的臨床和實(shí)驗(yàn)室診斷進(jìn)展下呼吸道標(biāo)本采集、運(yùn)送和處理規(guī)范無菌體液微生物檢驗(yàn)的規(guī)范流程臨床不常見菌的培養(yǎng)和快速鑒定藥敏試驗(yàn)折點(diǎn)建立和抗菌藥物的PK/PD2012年CLSI藥敏試驗(yàn)更新細(xì)菌耐藥監(jiān)測(cè)和藥敏譜統(tǒng)計(jì)的規(guī)范方法最新CLSI推薦的分枝桿菌、奴卡菌、其他需氧放線菌的藥敏試驗(yàn)規(guī)程病原微生物的快速分子診斷進(jìn)展病原菌的分子進(jìn)化研究進(jìn)展實(shí)驗(yàn)室的生物安全、質(zhì)量控制和質(zhì)量保證厭氧菌和彎曲菌的培養(yǎng)、鑒定和藥敏試驗(yàn)新進(jìn)展微生物檢驗(yàn)與Lis系統(tǒng)“感染性疾病的病原學(xué)診斷及臨床應(yīng)用新進(jìn)展學(xué)習(xí)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.商業(yè)系統(tǒng)MUST使用FDA折點(diǎn)June2010(M100-S20U)2011breakpointsprimarilybasedon:Verylimitedclinicaldata(nopatientswithMICsat0.Pages52-60.真菌病的實(shí)驗(yàn)室診斷和新進(jìn)展*目前和FDA折點(diǎn)相同5μg/mlMICssuggestedclinicalresponse)CeftizoximeTicarcillin-clavulanicacidVerylimitedclinicaldata(nopatientswithMICsat0.CloverleafAssayforβ-lactamase2011breakpointsprimarilybasedon:Staphylococcusspp.andFluoroquinolonesaureusQC:

Neg-ATCC25923Pages52-60.SIRThesedosageregimencommentsarenotintendedforuseonindividualpatientreports.Ceftazidime細(xì)菌耐藥監(jiān)測(cè)和藥敏譜統(tǒng)計(jì)的規(guī)范方法Pseudomonasaeruginosa

Penicillins+/-β-lactamaseInhibitorsDateofRevision*Pages52-60.美羅培南MIC(μg/ml)AllNew2012!(如ESBL或碳青霉烯酶)(13)Interpretivecriteriaforimipenemandmeropenemarebasedonadosageregimenof1gevery8h.lugdunensis“Incaseswherespecificdosageregimensareimportantforproperapplicationofbreakpoints,thedosageregimenislisted.謝謝觀看！(M100version)Verylimitedcli57革蘭陰性菌耐藥折點(diǎn)問題文檔ppt革蘭陰性菌耐藥折點(diǎn)問題文檔ppt58M100-S22PartialTableofContentsM100-S22.Page9.4M100-S22M100-S22.Page9.459更新的的總結(jié)

M100-S22.Page13.5更新的M100-S22.Page13.5602012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!62012主要變化腸桿菌科New!661M100-S22.P222010年后折點(diǎn)變化過程N(yùn)ew!7M100-S22.P222010年后折點(diǎn)變化過程N(yùn)ew!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腸桿菌科：

碳靑霉烯類

腸桿菌科：

碳靑霉烯類

65革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件66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美國(guó)碳靑霉烯類耐藥腸桿菌科（CRE）的分布黃色：KPC酶；67CLSI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。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68Piperacillin-tazobactam

MICdistributionexampleBlue=wildtypeisolatesRed=isolateswithacquired“R”10Piperacillin-tazobactamMICdi69SerumConcentration(μg/ml)Time(hours)MICTimeaboveMICdosedoseCmax(peakconcentration)PK/PDGoal(“Target”)forβ-lactams=(%T>MIC)12Organism%Time>MIC腸桿菌科35%綠膿30%SerumConcentration(μg/ml)Tim70DMID2009年DMID2009年71革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件72革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件73Piperacillin-tazobactam6Carbapenemases(metallo-lactamases)（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。1 Correspondingdiskdiffusionbreakpointsalsorevised5MHTsameresultwithertapenemandmeropenem(andimipenem)disksCLSIvsFDAInterpretiveCriteriaPages52-60.*目前和FDA折點(diǎn)相同January2012(M100-S22)January2010(M100-S20)Pages52and56.andCiprofloxacin藥敏試驗(yàn)折點(diǎn)建立和抗菌藥物的PK/PDTicarcillin-clavulanicacid臨床實(shí)驗(yàn)室可以使用CLSI或FDA折點(diǎn)Red=isolateswithacquired“R”mechanism3Limbago,BM.2012年CLSI綠膿桿菌折點(diǎn)變化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!28CLSIDocumentMIC(μg/ml)DiskD75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為何多次進(jìn)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進(jìn)行耐藥機(jī)制的初篩試驗(yàn)進(jìn)行耐藥機(jī)制的特異確證試驗(yàn)若檢測(cè)到耐藥82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新的模式進(jìn)行藥敏試驗(yàn)并且使用以治療為目的報(bào)告藥敏結(jié)果僅以83降低哌拉西林、哌拉西林/他唑巴坦、替卡西林、替卡西林/克拉維酸折點(diǎn)Pseudomonasaeruginosaaeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Comment(23)Page47.January2011(M100-S21)PseudomonasaeruginosaNewM100-S221typhiandExtraintestinalPiperacillin-tazobactamMICdistributionexampleaureusQC:

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

Neg-ATCC25923IsolatesA-DareallISO15189與微生物檢驗(yàn)3Limbago,BM.CLSIAgendabook.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。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.(舊折點(diǎn))(當(dāng)前折點(diǎn))MHT檢測(cè)碳青霉烯酶35M100-S22.(舊折點(diǎn))(當(dāng)前折點(diǎn))MHT檢測(cè)碳青霉烯85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)*陽性陰性陽性陰性報(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)碳青霉烯類藥物MIC

報(bào)告策略例#1例#2美羅培南M86如果用舊折點(diǎn)和碳青霉烯酶篩選試驗(yàn)陽性如果用當(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如果用如果用進(jìn)行MHT進(jìn)行MHT為何做MHT?M100-87革蘭陰性菌耐藥折點(diǎn)問題實(shí)用版課件88綠膿桿菌57綠膿桿菌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.2012年CLSI綠膿桿菌折點(diǎn)變化BPiperacilli92SectionIII. Therapy-RelatedComments

“Incaseswherespecificdosageregimensareimportantforproperapplicationofbreakpoints,thedosageregimenislisted.Thesedosageregimencommentsarenotintendedforuseonindividualpatientreports.”M100-S22.Instructions.Page28.New!60SectionIII. Therapy-RelatedC93最新CLSI推薦的分枝桿菌、奴卡菌、其他需氧放線菌的藥敏試驗(yàn)規(guī)程AntimicrobialAgentβ-lactamasepositive臨床實(shí)驗(yàn)室可以使用CLSI或FDA折點(diǎn)ISO15189與微生物檢驗(yàn)SerumConcentration(μg/ml)DosagecommentsSIR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Ticarcillin-clavulanateJanuary2010(M100-S20)CLSIAgendaBookJune2011CLSIBreakpointAdditions/RevisionsSince2010Enterobacteriaceae進(jìn)行耐藥機(jī)制的初篩試驗(yàn)Therapy-RelatedComments*目前和FDA折點(diǎn)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推薦的分枝桿菌、奴卡菌、其他需氧放線菌的藥敏試驗(yàn)94Outcomesofbacteremia(N=34episodes)duetoP.aeruginosawithreducedsusceptibilitytopiperacillin-tazobactam…Tametal.2008.Cli