重癥患者真菌感染聚焦念珠菌和氟康唑的地位

重癥患者侵襲性真菌感染——聚焦念珠菌感染及氟康唑地位唐建國(guó)

Trauma-Emergency-CriticalCareMedicineCenter(T-E-CCMC)重癥患者真菌感染聚焦念珠菌和氟康唑的地位1/83提要ICU與感染危重病人侵襲性真菌感染念珠菌起源抗真菌藥品及選擇關(guān)于氟康唑重癥患者真菌感染聚焦念珠菌和氟康唑的地位2/83提要ICU與感染危重病人侵襲性真菌感染念珠菌起源抗真菌藥品及選擇關(guān)于氟康唑重癥患者真菌感染聚焦念珠菌和氟康唑的地位3/83ICU感染患者感染性疾病診治感染預(yù)防與控制重癥感染入住ICUICU取得感染

（ICU-acquiredinfections）ICU內(nèi)取得性感染預(yù)防與控制感染相關(guān)問題是ICU永恒主題ICU工作關(guān)鍵點(diǎn)之一是感染重癥患者真菌感染聚焦念珠菌和氟康唑的地位4/8375countries1265ICUS13796patients7087(51.4%)infectedpatients9084(71%)receivingantibioticsICUmortalityrate25%(infected)&11%(non-infected)(p<.001)Infectionaccountedfor40%oftotalICUexpenditures重癥患者真菌感染聚焦念珠菌和氟康唑的地位5/83Siteofinfection7087(51.4%of13796

)Respiratorytract450363.5%Abdominal139219.6%Bloodstream107115.1%Renal/urinarytract101114.3%Skin4676.6%Catheter-related3324.7%CNS2082.9%重癥患者真菌感染聚焦念珠菌和氟康唑的地位6/83DistributionofNosocomialInfectionsbySiteinMedical-SurgicalICUinUSInfectControlHospEpidemiol.;21:510-515.重癥患者真菌感染聚焦念珠菌和氟康唑的地位7/83DistributionofNosocomialInfectionsbySiteinMedical-SurgicalICUinUSInfectionsatthreemajorsitesrepresented68%ofallreportedinfections

Nosocomialpneumonia31%Urinarytractinfections(UTIs)23%Bloodstreaminfections(BSIs)14%83%ofepisodesofnosocomialpneumoniawereassociatedwithmechanicalventilation(VAP)97%ofUTIsoccurredincatheterizedpatients(CAUTI)87%ofprimaryBSIsinpatientswithacentralline(CRBSI)重癥患者真菌感染聚焦念珠菌和氟康唑的地位8/83ICU與感染ICU感染病人：呼吸、腹腔、泌尿、血流ICU取得感染：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工作關(guān)鍵點(diǎn)之一是感染(51%感染病人）重癥患者真菌感染聚焦念珠菌和氟康唑的地位9/83提要ICU與感染危重病人侵襲性真菌感染真菌感染診療相關(guān)問題抗真菌藥品抗真菌藥品選擇重癥患者真菌感染聚焦念珠菌和氟康唑的地位10/83ICU感染病原學(xué)細(xì)菌(G+;G-;厭氧菌)不經(jīng)典細(xì)菌真菌病毒etc…重癥患者真菌感染聚焦念珠菌和氟康唑的地位11/83Mycoses.,55:435–443日本Toho1955-年間10297例尸檢進(jìn)行分析重癥患者真菌感染聚焦念珠菌和氟康唑的地位12/83Mycoses.,55:435–443重癥患者真菌感染聚焦念珠菌和氟康唑的地位13/83Among2,984ICUadmissions,therewere489deaths222autopsieswereconductedPostmortemexaminationrevealedunexpectedfindingsin50patientsIntensiveCareMed.,30:2080–2085Malignancy22Fungalinfections(mostaspergilosis)9Pulmonaryembolism7Nosocomialinfections3Other重癥患者真菌感染聚焦念珠菌和氟康唑的地位14/83Criticalandurgentcare:61-73重癥患者真菌感染聚焦念珠菌和氟康唑的地位15/83Positiveisolates(4947/7087=70%)Gram-negative307762.20%Gram-positive231546.80%FungiCandida84317%Aspergillus701.4%Others501.0%VincentJL,etal.JAMA.,302(21):2323-2329.重癥患者真菌感染聚焦念珠菌和氟康唑的地位16/83TortoranoAMetal.Mycoses.,55:73–79.May-April38ICUsof27Italianhospitals384fungalinfections(318invasiveCandidainfections,63mouldinfections

and3cryptococcosis)werenotified.Aspergillus57Mucormycosis4Fusariumverticillioides1Trichodermasp1CandidaAspergillusCryptococcosisMucormycosis重癥患者真菌感染聚焦念珠菌和氟康唑的地位17/8318ICUs18-monthstudy105episodesIFIsoccurredin5,561PatientsCandida:16.5cases/1,000admissionsFilamentousfungi:2.3cases/1,000admissionsFilamentousfungi:mainlyinvasivepulmonaryaspergillosis(IPA)重癥患者真菌感染聚焦念珠菌和氟康唑的地位18/83GuoF,etal.JAntimicrobChemother.,68(7):1660-8.

重癥患者真菌感染聚焦念珠菌和氟康唑的地位19/83中國(guó)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其它不動(dòng)桿菌屬81.3412重癥患者真菌感染聚焦念珠菌和氟康唑的地位20/83MicrobiologyofPeritonitis1.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)1重癥患者真菌感染聚焦念珠菌和氟康唑的地位21/83最初1-4周病原特征重癥患者真菌感染聚焦念珠菌和氟康唑的地位22/83KoreanJUrol.;54:59-65重癥患者真菌感染聚焦念珠菌和氟康唑的地位23/83ESBL53.1%ESBL37.5%重癥患者真菌感染聚焦念珠菌和氟康唑的地位24/83WisplinghoffH,etal.ClinicalInfectiousDiseases.;39:309–171995-Nosocomialbloodstreamisolates(SCOPEStudy)49UShospitals7-year24,179casesSurveillanceandControlofPathogensofEpidemiological重癥患者真菌感染聚焦念珠菌和氟康唑的地位25/83NosocomialBloodstreamIsolates(SCOPEStudy)9.8%23.2%67.0%WisplinghoffH,etal.ClinicalInfectiousDiseases.;39:309–17重癥患者真菌感染聚焦念珠菌和氟康唑的地位26/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位27/83TortoranoAMetal.Mycoses.,55,73–79.重癥患者真菌感染聚焦念珠菌和氟康唑的地位28/83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)重癥患者真菌感染聚焦念珠菌和氟康唑的地位29/83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重癥患者真菌感染聚焦念珠菌和氟康唑的地位30/83提要ICU與感染危重病人侵襲性真菌感染念珠菌起源抗真菌藥品及選擇關(guān)于氟康唑重癥患者真菌感染聚焦念珠菌和氟康唑的地位31/83C.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非白念重癥患者真菌感染聚焦念珠菌和氟康唑的地位32/83CandidaColonizationPulmonarytreeBowelVaginaEsophageal/GI重癥患者真菌感染聚焦念珠菌和氟康唑的地位33/83Candida:InfectionsitesC.parapsilosisC.tropicalisC.albicansC.kruseiC.glabrata重癥患者真菌感染聚焦念珠菌和氟康唑的地位34/83TheSourceofCandidemiaClinicalInfectiousDiseases.,33:1959-67重癥患者真菌感染聚焦念珠菌和氟康唑的地位35/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位36/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位37/83GItractGItractModelforInvasiveCandidiasis

Blijlevens,Donnelly,DePauw.BritJHaematol;117:259-64insultinjurytranslocationinfectionantibioticsselectionNormalcommensalfloraDiseaseCentralvenouscatheterCandidaspeciesGItract重癥患者真菌感染聚焦念珠菌和氟康唑的地位38/83LancetInfectDis..3:685-702重癥患者真菌感染聚焦念珠菌和氟康唑的地位39/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位40/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位41/83NatRevMicrobiol..10(2):112-122重癥患者真菌感染聚焦念珠菌和氟康唑的地位42/83NatRevMicrobiol..10(2):112-122重癥患者真菌感染聚焦念珠菌和氟康唑的地位43/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位44/83念珠菌起源外源性：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(yíng)養(yǎng)定植&高負(fù)荷定植&感染重癥患者真菌感染聚焦念珠菌和氟康唑的地位45/83提要ICU與感染危重病人侵襲性真菌感染念珠菌起源抗真菌藥品及選擇關(guān)于氟康唑重癥患者真菌感染聚焦念珠菌和氟康唑的地位46/83系統(tǒng)性抗真菌藥：全球isavuconazoleravuconazolefluconazoleitraconazoleposaconazoleL-AMBABCDABLCvoriconazolecaspofunginmicafunginanidulafunginAmphotericinBAzolesCandinsAMB重癥患者真菌感染聚焦念珠菌和氟康唑的地位47/83PhospholipidbilayerofthefungalcellmembraneFungalcellwallb-(1,3)-glucanb-(1,6)-glucanb-(1,3)-glucansynthaseGlucanSynthesisInhibitorEchinocadinCaspofunginMicafungin(FK463)Anidulafungin(LY303,306)ErgosterolPolyenes(AmB,LFAB)AzolesFluconazole,ItraconazoleVoriconazolePosaconazoleRavuconazole(BMS-207,147)AntifungalMechanismsofAction:

“Newer”AntifungalAgentsnucleusNucleosideAnalogsFlucytosine重癥患者真菌感染聚焦念珠菌和氟康唑的地位48/83MayoClinProc.;86(8):805-817重癥患者真菌感染聚焦念珠菌和氟康唑的地位49/83GeneralpatternsofsusceptibilityofCandidaSpp.IDSAGuidelines.CID2009,48:503–35重癥患者真菌感染聚焦念珠菌和氟康唑的地位50/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位51/83CHIF-NET重癥患者真菌感染聚焦念珠菌和氟康唑的地位52/83Journalofclinicalmicrobiology.,48(4):1366–1377重癥患者真菌感染聚焦念珠菌和氟康唑的地位53/83InvitrosusceptibilitiesofCandidaspp.to?uconazoleandvoriconazoleJournalofclinicalmicrobiology.,48(4):1366–1377重癥患者真菌感染聚焦念珠菌和氟康唑的地位54/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位55/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位56/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位57/83

IDSA：CandidiasisGuideline重癥患者真菌感染聚焦念珠菌和氟康唑的地位58/83重癥患者真菌感染聚焦念珠菌和氟康唑的地位59/83IntensiveCareMed.,35:206–214重癥患者真菌感染聚焦念珠菌和氟康唑的地位60/83Carmelilikescore重癥患者真菌感染聚焦念珠菌和氟康唑的地位61/83AntifungalsystemictherapyaccordingtoCarmeli-likescore重癥患者真菌感染聚焦念珠菌和氟康唑的地位62/83Carmeli-likescoreextendedantifungaltherapyalgorithm重癥患者真菌感染聚焦念珠菌和氟康唑的地位63/83抗真菌藥品及選擇抗真菌藥品選擇唑類、多烯類、棘白菌素類機(jī)制抗真菌譜嚴(yán)重程度粒細(xì)胞三唑類暴露局部流行病學(xué)CarmeliScore重癥患者真菌感染聚焦念珠菌和氟康唑的地位64/83提要ICU與感染危重病人侵襲性真菌感染念珠菌起源抗真菌藥品及選擇關(guān)于氟康唑重癥患者真菌感染聚焦念珠菌和氟康唑的地位65/83TheDosageofFluconazoleAAC.1998,42(5):1105-1109T>MICCmax/MICAUC/MIC重癥患者真菌感染聚焦念珠菌和氟康唑的地位66/83抗真菌藥品按PK/PD分類IntJAntimicrobAgents.Jan;39(1):1-10.重癥患者真菌感染聚焦念珠菌和氟康唑的地位67/83Fluconazoledose&CmaxandAUC重癥患者真菌感染聚焦念珠菌和氟康唑的地位68/83FungaldensitiesinkidneysofmicetreatedwithvariousFluconazole重癥患者真菌感染聚焦念珠菌和氟康唑的地位69/83PharmacodynamicvariablesforfivetotaldosesofFluconazoleED16ED37ED49ED60ED75重癥患者真菌感染聚焦念珠菌和氟康唑的地位70/83Dose-responsecurve重癥患者真菌感染聚焦念珠菌和氟康唑的地位71/83p=0.009重癥患者真菌感染聚焦念珠菌和氟康唑的地位72/83AAC.,51(10):3599-3604重癥患者真菌感染聚焦念珠菌和氟康唑的地位73/83CorrelationofMICdatawith

Fluconazoletreatmentsuccess重癥患者真菌感染聚焦念珠菌和氟康唑的地位74/83CorrelationofDose/MICandAUC/MIC

versusoutcomes重癥患者真菌感染聚焦念珠菌和氟康唑的地位75/83氟康唑劑量/MIC≥50時(shí)臨床有效率可達(dá)86%以上氟康唑不一樣給藥劑量/MIC比值治療粘膜/侵襲性念珠菌病總體臨床治愈率PfallerMA.ClinicalMicrobiologyReviews.;19(2):435-47.三項(xiàng)侵入性念珠菌病研究及一項(xiàng)粘膜感染研究匯總結(jié)果劑量/MIC有效率(%)68%86%95%98%55%020406080100<6.2550-75100-300≥40036/6552/7753/62135/142123/1256.25-12.5重癥患者真菌感染聚焦念珠菌和氟康唑的地位76/83PK/PDofFluconazoleDoseDependentAgentAUC/MIC45-90Dose/MIC50-