临床医生如何看待真菌感染与定植

临床医生如何看待真菌感染与定植2024/11/23内容提要侵袭性曲霉感染误诊分析

念珠菌定植问题腹腔念珠菌感染诊治问题123真菌概述酵母菌属曲霉菌属深部真菌感染念珠菌属隐球菌属常见的侵袭性念珠菌感染部位

定植不是感染定植不是与感染没有一点关系定植≠感染侵袭性真菌病确诊(proven)诊断标准正常无菌部位并不包括所有与外界相通的器官，即呼吸道、泌尿生殖道、消化道等，因为上述器官是念珠菌属常见的定植部位。念珠菌病诊断与治疗:专家共识.中国感染与化疗杂志.2011；11（2）:81-95念珠菌属于类酵母样菌,有酵母相和菌丝相酵母相为芽生孢子,在无症状寄居及传播中起作用,不引起症状菌丝相为芽生孢子伸长呈假菌丝,大量繁殖,侵袭组织能力加强,出现临床症状

需要注意的是,念珠菌中的光滑念珠菌不能产生假菌丝/菌丝,所以,临床不能因为“镜检念珠菌处于酵母相”就排除感染酵母相菌丝相念珠菌多为假菌丝念珠菌镜检假菌丝或菌丝

ColonizationwithCandidahasbeenidentifiedasanimportantriskfactorwithhighpredictivevaluefordevelopmentofinvasivedisease(particularlywithincreasingnumbersofcolonizedsites).

念珠菌定植

侵袭性念珠菌感染定植菌争议的焦点Invasivecandidiasisintheintensivecareunit.CritCareMed2006.34(3):857-863EggimannP，GarbinoJ，PittetD．EpidemiologyofCandidaspeciesinfectionsincriticallyillnon-immunosuppressedpatients．LancetInfectDis，2003，3(11):685-702．PK多部位念珠菌定植是发生侵袭性念珠菌感染的独立危险因素。念珠菌定植后导致侵袭性感染的途径可能有:破坏胃肠道黏膜屏障入血；从中心静脉导管入血，从局部感染蔓延至全身。定植与感染的关系LipsettPA．Surgicalcriticalcare=fungalinfectionsinsurgicalpatients．CritCareMed，2006，34(9Suppl):S215-224．约有50％～86％的重症患者发生念珠菌定植,但临床有5％～30％发展成严重侵袭性念珠菌感染。Althoughcolonizationdoesnotdefineinfection,thesedatasupportthewell-knownroleofCandidacolonizationasakeyfactorinthedecisiontostartearlyantifungaltreatmentforICUpatients.Abedsidescoringsystem(“Candidascore”)forearlyantifungaltreatmentinnonneutropeniccriticallyillpatientswithCandidaColonization.CritCareMed2006.34(3):730-737.定植与感染的死亡率S.S.Magilletal.DiagnosticMicrobiologyandInfectiousDisease55(2006)293–301进展为IC的百分比TheanatomicsiteofCandida

colonizationin182surgicalintensivecareunit(SICU)patientswho

participated

inarandomizedtrialoffluconazoletopreventcandidiasis.Atotalof2851surveillancefungalculturescollectedfrom5anatomicsiteswereanalyzed.SurveillancefungalculturesofparticularanatomicsitesmayhelpdifferentiatepatientsathigherriskofdevelopingICfromthoseatlowrisk.P=0.02P=0.04P=0.0113.2%2.8%8.0%1.2%8.4%0.0%定植可进展为侵袭性念珠菌病对于怀疑系统性念珠菌感染的患者,应同时进行痰(或其他气道分泌物)、尿、胃液、粪(或直肠拭子)、口咽拭子5个部位的念珠菌定量培养。口咽和直肠拭子念珠菌只要≥1cfu,胃液、尿≥105cfu/L,痰≥107cfu/L就认为念珠菌定植阳性。念珠菌定植指数(CI)PittetD，MonodM，SuterPM，eta1．Candidacolonizationandsubsequentinfectionsincriticallyillsurgicalpatients．AnnSurg，1994，220(6):751—758．口咽和直肠拭予念珠菌≥102cfu,胃液、尿、痰≥108cfu/L才能判定念珠菌定植阳性,如CI≥0.5或CCI≥0.4就认为有侵袭性念珠菌感染的可能。校正念珠菌定植指数(CCI)PiarrouxR，GrenouilletF，BalvayP，eta1.Assessmentofpre-emptivetreat—menttopreventseverecandidiasisincriticallyillsurgicalpatients.CritCareMed，2004，32(12)12443—2449.念珠菌指数(CS)将患者的危险系数相加,就得到该患者的CS。研究结果显示,CS>2.5时诊断侵袭性念珠菌感染的敏感性为81％,特异性为74％。CS=0.908×肠外营养支持+0.997×手术+1.112×CCI+2.038×严重脓毒症。LeanC，Ruiz—SuntansS，SaavedraP，eta1．Abedsidescoringsystem(”Candidascore”)forearlyantifungaltreatmentinnonneutropeniccriticallyi11patientswithCandidacolonization．CritCareMed，2006，34(3):730—737．InadditiontomultifocalCandidaspeciescolonization,threeotherriskfactorswerefoundtobesignificantpredictorsof

provencandidalinfectioninthelogisticregressionmodel:Useoftotalparenteralnutrition；SurgeryonICUadmission；Clinicalmanifestationsofseveresepsis.Score1121Abedsidescoringsystem(“Candidascore”)forearlyantifungaltreatmentinnonneutropeniccriticallyillpatientswithCandidaColonization.CritCareMed2006.34(3):730-737.Weshallonlyneedthepresenceofsepsisandanyoneofthethreeotherremainingriskfactorsorthepresenceofallofthemtogetherexceptsepsisinordertoconsiderstartingantifungaltreatmentforoneparticularpatient.LogisticregressionmodelAbedsidescoringsystem(“Candidascore”)forearlyantifungaltreatmentinnonneutropeniccriticallyillpatientswithCandidaColonization.CritCareMed2006.34(3):730-737.2008年亚太危重病论坛也指出,重症高危患者如同时具有高度念珠菌定植应予以抗念珠菌治疗,同时亦应考虑局部区域的真菌流行病学资料。要正确看待CI、CCI、CSHsuehPR，GraybillJR，PlayfordEG，eta1．ConsensusstatementonthemanagementofinvasivecandidiasiainintensivecareunitsintheAsia—Pacificregion．IntJAntimicrobAgents，2009，34(3):205—209．Eggimann等更明确地为抢先治疗下定义,即对具有多个侵袭性念珠菌感染高危因素且CCl≥0.4的脓毒症患者早期给予抗念珠菌治疗。定植菌抢先治疗的定义同时他认为实施抢先治疗可降低外科重症患者侵袭性念珠菌感染确诊病例的发生和降低病死率。EggimannP，GarbinoJ，PittetD．EpidemiologyofCandidaspeciesinfectionincriticallyillnon-immunosuppressedpatients．LancetInfectDis，2003，3(11):685—702．痰培养阳性的临床意义？如果患者存在明显的高危因素,有肺部感染的临床表现又不能用其他病原菌感染解释,血清真菌感染标志物（如G试验）阳性,此时痰培养念珠菌为唯一病原体且为反复培养阳性或为纯培养,可以作为针对念珠菌诊断性或经验性治疗的依据,至少提醒临床医生应提高警惕,特别是除肺外还有其他部位也分离到念珠菌时。怀疑念珠菌肺炎的患者在呼吸道标本检测的同时应做血液真菌培养,如血培养分离出念珠菌,且与呼吸道分泌物培养结果相一致,有助于念珠菌血症继发肺念珠菌病或肺炎合并念珠菌血症的诊断。2024/11/23内容提要侵袭性曲霉感染误诊分析

念珠菌定植问题腹腔念珠菌感染诊治问题12313吕新生,腹部外科2004年第17卷第3期腹腔脏器的感染腹膜腔感染病原体(主要是微生物)侵入宿主腹腔,且造成明显损害而引起的感染性疾病腹腔感染腹腔感染定义曹彬等.侵袭性念珠菌院内感染的流行病学调查.中华医学杂志2008;88(28)1970-1973白念珠菌（57.1％）热带念珠菌（19.5％）光滑念珠菌（14.3％）近平滑念珠菌（2.6％）念珠菌腹腔感染位居第二位常见的腹腔念珠菌感染念珠菌腹膜炎急性胰腺炎、胆囊炎合并念珠菌感染腹腔脓肿（念珠菌感染）腹腔念珠菌感染的高危因素1.SottoA,LefrantJY,Fabbro-PerayP,etal.Evaluationofantimicrobialtherapymanagementof120consecutivepatientswithsecondaryperitonitis.JAntimicrobChemother2002;50:569–576.2.CharlesPE.MultifocalCandidaspeciescolonizationasatriggerforearlyantifungaltherapyincriticallyillpatients:whataboutotherriskfactorsforfungalinfection?CritCareMed2006;34:913–914.PhilippeMontraversetal.Candidaasariskfactorformortalityinperitonitis.CritCareMed.2006;34(3):646-52一项多中心、回顾性对照研究,在教学及非教学医院的17个ICU进行其中确诊院内腹膜炎的患者中,腹水病原菌分离率以白念最多腹水中病原菌分离率(%)白念珠菌n=39肠杆菌科n=31肠球菌n=19厌氧菌n=11大肠杆菌n=15白念是腹腔感染的主要致病真菌ThierryCalandraetal.ClinicalTrialsofAntifungalProphylaxisamongPatientsUndergoingSurgery.CID.2004;39(4):S185-192腹腔侵袭性念珠菌感染的发生机制分离的念珠菌在腹腔感染中起致病作用争议目前大量的研究显示念珠菌腹腔感染死亡率高达:27%~77%强烈主张抗真菌的抢先治疗（经验治疗）ThierryCalandraetal.ClinicalTrialsofAntifungalProphylaxisamongPatientsUndergoingSurgery.CID.2004;39(4):S185-192对腹腔念珠菌感染的看法腹腔分离的念珠菌是“无辜的牵涉者”在271例ICU腹膜炎患者中,83例念珠菌腹膜炎患者DupontH,etal.ArchSurg.

2002Dec;137(12):1341-6.死亡率(%)N=83N=188念珠菌腹膜炎非念珠菌腹膜炎11%念珠菌腹膜炎死亡率高比利时的Ghent大学医院感染疾病中心的ICU,对1995.1-2002.12入住ICU的急性重症胰腺炎胰腺坏死感染的患者46例进行分析,分析真菌感染发生率JanJ.DeWaeleetal.CID2003;37(7):208-213胰腺真菌感染的真菌菌种分布:白念珠菌为主SAP真菌感染几乎全部为念珠菌SAP合并念珠菌感染与细菌感染的不同AmJGastroenterol.2009Aug;104(8):2065-70.1992-2001,207例SAP患者52例确认有细菌感染（IBI）,其中30例(15%)合并真菌感染（IFI）,7例原发,23例继发IFI57.7%Antibiotic40%~100%TPN42%~85%5%~68%AmJGastroenterol.2011Jul;106(7):1188-92.SAP合并腹腔念珠菌感染:荟萃分析LocaltreatmentDebridementornecrosectomyMinimizationofintraoperativehemorrhageMaximizationofpostoperativeremovalofretroperitonealdebrisandexudatessystemicantifungaltreatmentneedstobestartedearlyinthecourseofthedisease.AmJGastroenterol.2011Jul;106(7):1188-92防治SAP合并腹腔念珠菌感染的措施腹腔念珠菌脓肿腹腔脓肿念珠菌腹腔感染中腹腔脓肿占:36.8%THIERRYCALANDRAetal.CLINICALSIGNIFICANCEOFCANDIDAISOLATEDFROMPERITONEUMINSURGICALPATIENTS.TheLancet.1989;December16.P1437-1440腹腔念珠菌脓肿发生率体会1.诊断问题体会2.治疗问题2024/11/23内容提要

侵袭性曲霉感染误诊分析

念珠菌定植问题腹腔念珠菌感染诊治问题123Meerssemanetal.ClinicalInfectiousDiseases2007;45:205–16COPD合并呼吸衰竭入住ICU，接受皮质激素治疗胸片:两肺局灶性渗出、模糊、右侧胸腔积液BAL培养:流感嗜血杆菌（+）、霉菌（-）血清GM（-）BALGM2.6ng/ml尸检:IPA例1.AECOPD呼吸衰竭患者Meerssemanetal.ClinicalInfectiousDiseases2007;45:205–16肝移植受体者胸片:右侧片状实变影，类似肺部感染BAL:细菌、霉菌（-）血清GM（-）尸检:播散性曲霉例2.肝移植患者Meerssemanetal.ClinicalInfectiousDiseases2007;45:205–16急性粒细胞白血病骨髓移植后接受高剂量抗排异治疗4月胸片：右侧肺片状渗出、胸腔积液CT：右侧肺局部实变影伴有空洞、有液平；第4.5肋骨破坏；左侧肺锲型实变影胸腔积液培养：烟曲霉例3.骨髓移植患者Meerssemanetal.ClinicalInfectiousDiseases2007;45:205–16晚期糖尿病肾移植2月胸片及CT:两下肺斑片状阴影伴空洞、右侧胸腔积液血清GM0.1ng/ml、BALGM5.7ng/ml经支气管活检:烟曲霉死于三尖瓣心内膜炎（曲霉）例4.肾移植患者这些病人如果没有活检或尸检的话,你会诊断侵袭性曲霉感染吗？IPA误诊的原因ThediagnosisofIPAinnon-neutropeniccriticallyillpatientsisdifficultsignsandsymptomsarenon-specific.Apositiveresultofacultureofarespiratoryspecimenorpositivefindingsofadirectmicroscopicexaminationonlyone-halfofpatientswithIPA.Thepredictivevalueofapositivecultureresultdependslargelyonwhetherthepatientisimmunocompromisedandrangesfrom20%to80%.1.Trofetal.IntensiveCareMed2007;33:1694–7032.HopeWW,WalshTJ,DenningDW.Laboratorydiagnosisofinvasiveaspergillosis.LancetInfectDis2005;5:609–22.3.TarrandJJ,LichterfeldM,WarraichI,etal.Diagnosisofinvasiveseptatemoldinfections:acorrelationofmicrobiologicalcultureandhistologicorcytologicexamination.AmJClinPathol2003;119:854–8.Meerssemanetal.ClinicalInfectiousDiseases2007;45:205–16IPA的危险因素GM抗原的敏感性与特异性CorrelateswithfungalburdeninanimalandclinicalstudiesSensitivityandspecificityLimitationsinnon-neutropenicpatients(SOT)DetectedinCSF,bronchoalveolarlavage(BAL)fluidSensitivity(%)

Specificity(%)HSCT

8992Livertransplant55.693.9~98.5Lungtransplant9530Serologictestingtechniquesofgalactomannan(GM)holdpromiseforpatientswithhematologicmalignancy.GMStudiesofneutropenicpatientshaverevealedhighratesofsensitivity(67%~100%)andspecificity(86%~99%).However,inaretrospectiveobservationalstudyofamedicalICUpopulation,serumGMwaselevatedinonly53%ofpatientswithIA.DetectionofserumGMisprobablenotasensitivemarkerforIA(especiallyinnon-neutropenicpatients).Meerssemanetal.ClinicalInfectiousDiseases2007;45:205–16GM试验在IPA的价值GMhastobestressedthattheavailabledatafrompatientswith(haematological)malignanciesandaftersolidorgantransplantationcannotbeextrapolatedtothecriticallyillpatientingeneral.Inthemeantime,duetolackofmorereliable,non-invasivediagnostictests,theGMassaycouldbeusedasanadditivetoolinthediagnosticwork-upofIPA.Trofetal.IntensiveCareMed2007;33:1694–703GM试验可以作为IPA的辅助诊断IPA高风险病人的诊治策略MoniqueASHMennink-Kersten,JPeterDonnelly,andPaulEVerweijTHELANCETInfectiousDiseasesVol4June2004possibleprobableproven38patientsprobable(n=28)proven(n=10).37%patients≥2riskfactorsforIA.AllprobableIAwerediagnosedbyBAL.ProvenIAwasreachedbypositivehistopathologicandcultureresultsofsamplesautopsy(n=4)percutaneous(n=3)transbronchialbiopsy(n=3).A.Hidalgoetal./EuropeanJournalofRadiology71(2009)55–60HRCT与GM的相关性HRCT分类Airwayinvasiveaspergillosis

气道侵袭性曲霉病Aspergillusbronchiolitis（“tree-in-bud”pattern）Aspergillusbronchopneumonia（air-spaceconsolidation）angioinvasiveaspergillosis

血管侵袭性曲霉病“halo”ofground-glass“air-crescentsign”LoganPM,PrimackSL,MillerRR,MullerNL.Invasiveaspergillosisoftheairways:radiographic,CT,andpathologicfindings.Radiology1994;193:383–8.2.FranquetT,MullerNL,Gim´enezA,GuembeP,delaTorreJ,Bagu´eS.Spectrumofpulmonaryaspergillosis:histologic,clinical,andradiologicsigns.Radiographics2001;21:825–37.气道侵袭性曲霉病A.Hidalgoetal./EuropeanJournalofRadiology71(2009)55–60GM:0.7~0.9GM:0.6~1.0血管侵袭性曲霉病A.Hidalgoetal./EuropeanJournalofRadiology71(2009)55–60GM:2.2GM:1.7~2.0HRCT与GM在IPA的相关性A.Hidalgoetal./EuropeanJournalofRadiology71(2009)5