重癥患者真菌感染聚焦念珠菌和氟康唑的地位培訓(xùn)課件

重癥患者真菌感染聚焦念珠菌和氟康唑的地位提要ICU與感染危重病人侵襲性真菌感染念珠菌來源抗真菌藥物及選擇關(guān)于氟康唑2重癥患者真菌感染聚焦念珠菌和氟康唑的地位提要ICU與感染危重病人侵襲性真菌感染念珠菌來源抗真菌藥物及選擇關(guān)于氟康唑3重癥患者真菌感染聚焦念珠菌和氟康唑的地位ICU感染患者感染性疾病診治感染的預(yù)防與控制重癥感染入住ICUICU獲得感染

（ICU-acquiredinfections）ICU內(nèi)獲得性感染的預(yù)防與控制感染相關(guān)問題是ICU永恒主題ICU工作要點(diǎn)之一是感染4重癥患者真菌感染聚焦念珠菌和氟康唑的地位75countries1265ICUS13796patients7087(51.4%)infectedpatients9084(71%)receivingantibioticsICUmortalityrate25%(infected)&11%(non-infected)(p<.001)Infectionaccountedfor40%oftotalICUexpenditures5重癥患者真菌感染聚焦念珠菌和氟康唑的地位Siteofinfection7087(51.4%of13796

)Respiratorytract450363.5%Abdominal139219.6%Bloodstream107115.1%Renal/urinarytract101114.3%Skin4676.6%Catheter-related3324.7%CNS2082.9%6重癥患者真菌感染聚焦念珠菌和氟康唑的地位DistributionofNosocomialInfectionsbySiteinMedical-SurgicalICUinUSInfectControlHospEpidemiol.2000;21:510-515.7重癥患者真菌感染聚焦念珠菌和氟康唑的地位DistributionofNosocomialInfectionsbySiteinMedical-SurgicalICUinUSInfectionsatthreemajorsitesrepresented68%ofallreportedinfections

Nosocomialpneumonia31%Urinarytractinfections(UTIs)23%Bloodstreaminfections(BSIs)14%83%ofepisodesofnosocomialpneumoniawereassociatedwithmechanicalventilation(VAP)97%ofUTIsoccurredincatheterizedpatients(CAUTI)87%ofprimaryBSIsinpatientswithacentralline(CRBSI)8重癥患者真菌感染聚焦念珠菌和氟康唑的地位ICU與感染ICU感染病人：呼吸、腹腔、泌尿、血流ICU獲得感染：呼吸、泌尿、血流、(手術(shù)部位-SICU)感染相關(guān)問題是ICU永恒主題ICU工作要點(diǎn)之一是感染(51%感染病人）9重癥患者真菌感染聚焦念珠菌和氟康唑的地位提要ICU與感染危重病人侵襲性真菌感染真菌感染診斷相關(guān)問題抗真菌藥物抗真菌藥物選擇10重癥患者真菌感染聚焦念珠菌和氟康唑的地位ICU感染的病原學(xué)細(xì)菌(G+;G-;厭氧菌)不典型細(xì)菌真菌病毒etc…11重癥患者真菌感染聚焦念珠菌和氟康唑的地位Mycoses.2012,55:435–443日本Toho1955-2006年間的10297例尸檢進(jìn)行分析12重癥患者真菌感染聚焦念珠菌和氟康唑的地位Mycoses.2012,55:435–44313重癥患者真菌感染聚焦念珠菌和氟康唑的地位Among2,984ICUadmissions,therewere489deaths222autopsieswereconductedPostmortemexaminationrevealedunexpectedfindingsin50patientsIntensiveCareMed.2004,30:2080–2085Malignancy22Fungalinfections(mostaspergilosis)9Pulmonaryembolism7Nosocomialinfections3Other14重癥患者真菌感染聚焦念珠菌和氟康唑的地位Criticalandurgentcare:61-7315重癥患者真菌感染聚焦念珠菌和氟康唑的地位Positiveisolates(4947/7087=70%)Gram-negative307762.20%Gram-positive231546.80%FungiCandida84317%Aspergillus701.4%Others501.0%VincentJL,etal.JAMA.2009,302(21):2323-2329.16重癥患者真菌感染聚焦念珠菌和氟康唑的地位TortoranoAMetal.Mycoses.2011,55:73–79.May2006-April200838ICUsof27Italianhospitals384fungalinfections(318invasiveCandidainfections,63mouldinfections

and3cryptococcosis)werenotified.Aspergillus57Mucormycosis4Fusariumverticillioides1Trichodermasp1CandidaAspergillusCryptococcosisMucormycosis17重癥患者真菌感染聚焦念珠菌和氟康唑的地位18ICUs18-monthstudy105episodesIFIsoccurredin5,561PatientsCandida:16.5cases/1,000admissionsFilamentousfungi:2.3cases/1,000admissionsFilamentousfungi:mainlyinvasivepulmonaryaspergillosis(IPA)18重癥患者真菌感染聚焦念珠菌和氟康唑的地位GuoF,etal.JAntimicrobChemother.2013,68(7):1660-8.

19重癥患者真菌感染聚焦念珠菌和氟康唑的地位中國16家大型教學(xué)醫(yī)院HAP臨床調(diào)查(599例分離到694株菌)病原菌菌株數(shù)%病例數(shù)Sort鮑曼不動(dòng)桿菌17529.221銅綠假單胞菌12520.872金黃色葡萄球菌7712.853肺炎克雷伯桿菌589.684白色念珠菌355.845嗜麥芽窄食單胞菌274.516大腸埃希菌203.347陰溝腸桿菌132.178醋酸鈣不動(dòng)桿菌40.6720其他不動(dòng)桿菌屬81.341220重癥患者真菌感染聚焦念珠菌和氟康唑的地位MicrobiologyofPeritonitis1.LarocheM,HardingG.EurJClinMicrobiolInfectDis.1998;17:542-550.2.BariePS.JChemother.1999;11:464-477.B.fragilisgroupClostridiumspp.EnterococciS.EpidermidisMRSAPseudomonas+A.baumanniiCandidaB.fragilisgroupClostridiumspp.E.coliKlebsiellaspp.StreptococcusEnterococcusspp.CandidaE.coliKlebsiellaspp.Streptococcusspp.Tertiary(Polymicrobial)2Secondary(Polymicrobial)1,2Primary(Monomicrobial)121重癥患者真菌感染聚焦念珠菌和氟康唑的地位最初1-4周病原特征22重癥患者真菌感染聚焦念珠菌和氟康唑的地位KoreanJUrol.2013;54:59-6523重癥患者真菌感染聚焦念珠菌和氟康唑的地位ESBL53.1%ESBL37.5%24重癥患者真菌感染聚焦念珠菌和氟康唑的地位WisplinghoffH,etal.ClinicalInfectiousDiseases.2004;39:309–171995-2002Nosocomialbloodstreamisolates(SCOPEStudy)49UShospitals7-year24,179casesSurveillanceandControlofPathogensofEpidemiological25重癥患者真菌感染聚焦念珠菌和氟康唑的地位NosocomialBloodstreamIsolates(SCOPEStudy)9.8%23.2%67.0%WisplinghoffH,etal.ClinicalInfectiousDiseases.2004;39:309–1726重癥患者真菌感染聚焦念珠菌和氟康唑的地位27重癥患者真菌感染聚焦念珠菌和氟康唑的地位TortoranoAMetal.Mycoses.2011,55,73–79.28重癥患者真菌感染聚焦念珠菌和氟康唑的地位危重病人侵襲性真菌感染Candida、Aspergillus、Cryptococcosis、MucormycosisICU:60%(-);40%(+);20%(Fungal,mostlycandida)呼吸(Candida5)腹腔(繼發(fā)性、第三類型腹膜炎）泌尿(Candida2-4)血流((Candida3)29重癥患者真菌感染聚焦念珠菌和氟康唑的地位其它部位消化系統(tǒng)、骨關(guān)節(jié)、心血管系統(tǒng)等念珠菌最為常見腹腔感染以念珠菌最為常見（除外近平滑）真菌血流感染呼吸系統(tǒng)泌尿系統(tǒng)中樞神經(jīng)系統(tǒng)以隱球菌多見念珠菌，曲霉菌少見常見病原體為曲霉菌和念珠菌、隱球菌（煙曲霉）以念珠菌最為常見(近平滑）以念珠菌尿最為多見（除外近平滑）侵襲性真菌感染危重病人侵襲性真菌感染30重癥患者真菌感染聚焦念珠菌和氟康唑的地位提要ICU與感染危重病人侵襲性真菌感染念珠菌來源抗真菌藥物及選擇關(guān)于氟康唑31重癥患者真菌感染聚焦念珠菌和氟康唑的地位C.Albicans(白色念）C.Glabrata（光滑念）C.parapsilosis（近平滑念）C.Tropicalis（熱帶念）C.Krusei（克柔念）C.Guilliermondii（季也蒙念）C.Lusitaniae（葡萄牙念）C.inconspicuaC.norvegensisC.dubliniensisC.lipolyticaC.zeylanoidesC.pelliculosaCandidaspp.C.kefyrC.rugosaC.famataCandidaSPP.(>165species)C.Albican

白念NonC.Albicans非白念32重癥患者真菌感染聚焦念珠菌和氟康唑的地位CandidaColonizationPulmonarytreeBowelVaginaEsophageal/GI33重癥患者真菌感染聚焦念珠菌和氟康唑的地位Candida:InfectionsitesC.parapsilosisC.tropicalisC.albicansC.kruseiC.glabrata34重癥患者真菌感染聚焦念珠菌和氟康唑的地位TheSourceofCandidemiaClinicalInfectiousDiseases.2001,33:1959-6735重癥患者真菌感染聚焦念珠菌和氟康唑的地位36重癥患者真菌感染聚焦念珠菌和氟康唑的地位37重癥患者真菌感染聚焦念珠菌和氟康唑的地位GItractGItractModelforInvasiveCandidiasis

Blijlevens,Donnelly,DePauw.BritJHaematol2002;117:259-64insultinjurytranslocationinfectionantibioticsselectionNormalcommensalfloraDiseaseCentralvenouscatheterCandidaspeciesGItract38重癥患者真菌感染聚焦念珠菌和氟康唑的地位LancetInfectDis.2003.3:685-70239重癥患者真菌感染聚焦念珠菌和氟康唑的地位40重癥患者真菌感染聚焦念珠菌和氟康唑的地位41重癥患者真菌感染聚焦念珠菌和氟康唑的地位NatRevMicrobiol.2013.10(2):112-12242重癥患者真菌感染聚焦念珠菌和氟康唑的地位NatRevMicrobiol.2013.10(2):112-12243重癥患者真菌感染聚焦念珠菌和氟康唑的地位44重癥患者真菌感染聚焦念珠菌和氟康唑的地位念珠菌來源外源性：導(dǎo)管位置、導(dǎo)管護(hù)理內(nèi)源性：胃腸粘膜保護(hù)、腸內(nèi)營養(yǎng)定植&高負(fù)荷定植&感染45重癥患者真菌感染聚焦念珠菌和氟康唑的地位提要ICU與感染危重病人侵襲性真菌感染念珠菌來源抗真菌藥物及選擇關(guān)于氟康唑46重癥患者真菌感染聚焦念珠菌和氟康唑的地位系統(tǒng)性抗真菌藥：全球isavuconazoleravuconazolefluconazoleitraconazoleposaconazoleL-AMBABCDABLCvoriconazolecaspofunginmicafunginanidulafunginAmphotericinBAzolesCandinsAMB47重癥患者真菌感染聚焦念珠菌和氟康唑的地位PhospholipidbilayerofthefungalcellmembraneFungalcellwallb-(1,3)-glucanb-(1,6)-glucanb-(1,3)-glucansynthaseGlucanSynthesisInhibitorEchinocadinCaspofunginMicafungin(FK463)Anidulafungin(LY303,306)ErgosterolPolyenes(AmB,LFAB)AzolesFluconazole,ItraconazoleVoriconazolePosaconazoleRavuconazole(BMS-207,147)AntifungalMechanismsofAction:

“Newer”AntifungalAgentsnucleusNucleosideAnalogsFlucytosine48重癥患者真菌感染聚焦念珠菌和氟康唑的地位MayoClinProc.2011;86(8):805-81749重癥患者真菌感染聚焦念珠菌和氟康唑的地位GeneralpatternsofsusceptibilityofCandidaSpp.IDSAGuidelines.CID2009,48:503–3550重癥患者真菌感染聚焦念珠菌和氟康唑的地位51重癥患者真菌感染聚焦念珠菌和氟康唑的地位CHIF-NET201052重癥患者真菌感染聚焦念珠菌和氟康唑的地位Journalofclinicalmicrobiology.2010,48(4):1366–137753重癥患者真菌感染聚焦念珠菌和氟康唑的地位InvitrosusceptibilitiesofCandidaspp.to?uconazoleandvoriconazoleJournalofclinicalmicrobiology.2010,48(4):1366–137754重癥患者真菌感染聚焦念珠菌和氟康唑的地位55重癥患者真菌感染聚焦念珠菌和氟康唑的地位56重癥患者真菌感染聚焦念珠菌和氟康唑的地位57重癥患者真菌感染聚焦念珠菌和氟康唑的地位

IDSA：CandidiasisGuideline200958重癥患者真菌感染聚焦念珠菌和氟康唑的地位59重癥患者真菌感染聚焦念珠菌和氟康唑的地位IntensiveCareMed.2009,35:206–21460重癥患者真菌感染聚焦念珠菌和氟康唑的地位Carmelilikescore61重癥患者真菌感染聚焦念珠菌和氟康唑的地位AntifungalsystemictherapyaccordingtoCarmeli-likescore62重癥患者真菌感染聚焦念珠菌和氟康唑的地位Carmeli-likescoreextendedantifungaltherapyalgorithm63重癥患者真菌感染聚焦念珠菌和氟康唑的地位抗真菌藥物及選擇抗真菌藥物選擇唑類、多烯類、棘白菌素類機(jī)制抗真菌譜嚴(yán)重程度粒細(xì)胞三唑類暴露局部的流行病學(xué)CarmeliScore64重癥患者真菌感染聚焦念珠菌和氟康唑的地位提要ICU與感染危重病人侵襲性真菌感染念珠菌來源抗真菌藥物及選擇關(guān)于氟康唑65重癥患者真菌感染聚焦念珠菌和氟康唑的地位TheDosageofFluconazoleAAC.1998,42(5):1105-1109T>MICCmax/MICAUC/MIC66重癥患者真菌感染聚焦念珠菌和氟康唑的地位抗真菌藥物按PK/PD分類IntJAntimicrobAgents.2012Jan;39(1):1-10.67重癥患者真菌感染聚焦念珠菌和氟康唑的地位Fluconazoledose&CmaxandAUC68重癥患者真菌感染聚焦念珠菌和氟康唑的地位FungaldensitiesinkidneysofmicetreatedwithvariousFluconazole69重癥患者真菌感染聚焦念珠菌和氟康唑的地位Dose-responsecurve71重癥患者真菌感染聚焦念珠菌和氟康唑的地位p=0.00972重癥患者真菌感染聚焦念珠菌和氟康唑的地位AAC.2007,51(10):3599-360473重癥患者真菌感染聚焦念珠菌和氟康唑的地位CorrelationofMICdatawith

Fluconazoletreatmentsuccess74重癥患者真菌感染聚焦念珠菌和氟康唑的地位CorrelationofDose/MICandAUC/MIC

versusoutcomes75重癥患者真菌感染聚焦念珠菌和氟康唑的地位氟康唑劑量/MIC≥50時(shí)臨床有效率可達(dá)86%以上氟康唑不同給藥劑量/MIC比值治療粘膜/侵襲性念珠菌病總體臨床治愈率PfallerMA.ClinicalMicrobiologyReviews.2006;19(2):435-47.三項(xiàng)侵入性念珠菌病的研究及一項(xiàng)粘膜感染的研究的匯總結(jié)果劑量/MIC有效率(%)68%86%95%98%55%020406080100<6.2550-75100-300≥40036/6552/7753/62135/142123/1256.25-12.576重癥患者真菌感染聚焦念珠菌和氟康唑的地位PK/PDofFluconazoleDoseDependentAgentAUC/MIC45-90Dose/MIC50-100S≤8mg/l