念珠菌流行病学趋势与IDSA2009年念珠菌治疗指南江苏省人民医院周苏明2011年2月27日EpidemiologyofcandidemiainintensivecareunitsInternationalJournalofAntimicrobialAgents32Suppl.2(2008)S87–S91AgrowingproportionofepisodesofcandidemiahavebeencausedbyCandidaspeciesotherthanalbicans.•Epidemiology,management,andriskfactorsfordeathofinvasiveCandidainfectionsincriticalcare:Amulticenter,prospective,observationalstudyinFrance(2005–2006)(CritCareMed2009;37:1612–1618)•OnehundredeightyICUsinFrance.•BetweenOctober2005andMay2006,300adultpatientswithproveninvasiveCandidainfection.•107(39.5%)patientswithisolatedcandidemia,•87(32.1%)withinvasivecandidiasiswithoutdocumentedcandidemia,•77(28.4%)withinvasivecandidiasisandcandidemia.•In37%ofthecases,candidemiaoccurredwithinthefirst5daysafterICUadmission.ConsensusstatementonthemanagementofinvasivecandidiasisinIntensiveCareUnitsintheAsia-PacificRegionInternationalJournalofAntimicrobialAgents34(2009)205–209中国5所医院念珠菌属对氟康唑和伏立康唑的耐药性监测ARTEMIS朱德妹张婴元汪复中国感染与化疗杂志,2007,7(1):14~18•8000株念珠菌和酵母菌分别来自北京、杭州、广州和上海5所三级甲等医院临床微生物实验室和真菌室临床分离株•CandidaAlbicansVersusNon-AlbicansIntensiveCareUnit-AcquiredBloodstreamInfections:DifferencesinRiskFactorsandOutcomeANESTHESIA&ANALGESIAVol.106,No.2,February2008InvasivecandidiasisintheintensivecareunitLuisOstrosky-Zeichner,CritCareMed2006;34:857–863危险因素•ThemostimportantindependentconditionspredisposingtocandidemiainICUpatientsinclude:priorabdominalsurgery,intravascularcatheters,acuterenalfailure,parenteralnutrition,broad-spectrumantibiotics,aprolongedICUstay,theuseofcorticosteroidsandmucosalcolonizationwithCandida.InternationalJournalofAntimicrobialAgents32Suppl.2(2008)S87–S91ANESTHESIA&ANALGESIAVol.106,No.2,February2008MolecularbasisofresistancetoazoleantifungalsTRENDSinMolecularMedicineVol.8No.2February20021.唑类药物在细胞内的浓度降低:泵出机制:over-expressingABC-typeeffluxpumps,(over-expressingbothCDR1andCDR2)----Candidaalbicans,Candidaglabrata•OverexpressionofCDR1andCDR2inC.albicansisassociatedwithcross-resistancetotheazoles,andamorolfine2.唑类药物在细胞内的作用靶点水平增高•唑类药物的作用靶点是细胞色素P450,后者由EGR11(或CYP51)编码•InthecaseofaclinicalisolateofC.glabratacross-resistancetofluconazole,itraconazoleandketoconazolewascausedbytheduplicationoftheentirechromosomecontainingCYP51.3.甾醇合成改变4.唑类与细胞内靶点亲和力下降5.生物被膜:Exposureofbiofilmstofluconazoleinducedupregulationofgenesencodingenzymesinvolvedinergosterolbiosynthesis(ERG1,ERG3,ERG11andERG25).ResearchinMicrobiologyxx(2010)1-96.Fluconazoleatsubinhibitoryconcentrationsinducestheoxidative-andnitrosative-responsivegenesTRR1,GRE2andYHB1,andenhancestheresistanceofCandidaalbicanstophagocytes.JournalofAntimicrobialChemotherapy.65(1):54-62,January2010IFI的诊断----重症患者侵袭性真菌感染诊断和治疗指南•IFI的诊断由宿主因素、临床特征、微生物学检查和组织病理学四部分组成。•临床诊断IFI时要充分结合宿主因素,除外其他病原体所致的肺部感染或非感染性疾病。•诊断IFI分确诊、临床诊断及拟诊3个级别。IPFI的诊断标准宿主因素临床特征微生物学组织病理学确诊+*++△+临床诊断+++-拟诊++--注:*原发性者可无宿主因素,△肺组织、胸液、血液真菌培养阳性(除外肺孢子菌)宿主因素•(1)外周血中性粒细胞减少,中性粒细胞计数<0.5×109/L,且持续>10d;•(2)体温>38℃或<36℃,并伴有以下情况之...