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1、IntroductionInvasivefungalinfectionshaveincreasedsignificantlyoverthelast2decades.agingpopulationwithlifesustainingtherapieslikerenaldialysisbroadspectrumantimicrobialtherapyandinvasivemedicaldevicesbonemarrowtransplantation(BMT)&solidorgantransplantation(SOT)intensivechemothera
2、pyformalignanciesHIV/AIDSepidemic.NationalEpidemiologyofMycosisSurvey(NEMIS)wasaprospective,multicenterstudyconductedat6USsitesfrom1993–1995toexamineratesofriskfactorsforthedevelopmentofcandidalbloodstreaminfections(CBSIs)amongpatientsinsurgicalandneonatalintensivecareunits>48ho
3、urs.Among4276patients,42CBSIsoccurred.AdaptedfromBlumbergHMetal,andtheNEMISStudyGroupClinInfectDis2001;33:177–186;GarberGDrugs2001;61(suppl1):1–12.RiskforInvasiveMycosisNon-Neutropenicrelatedtobarrierbreakdown,changeincolonization.Acuterenalfailure(RR4.2)Parenteralnutritionwith
4、intralipid(RR3.6)PriorsurgeryspeciallyGI(RR7.3)Indwellingcentralline?Triplelumen(RR5.4)BroadspectrumantibioticsDiabetesBurnsMechanicalVentilationSteroidsNeutropenicrelatedtoaboveplusimmunecellsuppressionandunderlyingmalignancy.Severeimmunosuppressive:BMTorSOTInvasiveMycosisCandi
5、diasisAspergillosisDecreasingimmunitySOTorBMTMICUorSICUBarrierimmunityBarrierpluscellularimmunityOncologyPolyenesAmphotericinB(AmB)orLiposomalAmB(kidneytoxicity)AzolesFluconazole400-800mg/day(livertoxicity,CYP450)Voriconazole(livertoxicity,visualdisturbances,CYP450)Posaconazole(
6、livertoxicity,CYP450)EchinocandinsCaspofunginiv(livertoxicity)Combinationex.AmB/Fluconazole(liver,kidneytoxicity)Choiceofagentsdependsonwhetherthepatientonpreviousazoleprophylaxis,cultureresults,localfungalsensitivity,colonization,renalorliverdisease,presenceofdrug-druginteracti
7、ons,presenceofhardware,immuno-suppresion,siteofdiseaseex.urine.TreatmentofInvasiveMycosisSiteofActionofSelectedAnti-fungalAgentsAdaptedfromAndrioleVTJAntimicrobChemother1999;44:151–162;GraybillJRetalAntimicrobAgentsChemother1997;41:1775–1777;GrollAH,WalshTJExpertOpinInvestDrugs2
8、001;10(8):1545–1558.CellmembranePolyenesAmB(ste