ECCMID-曲霉菌指南簡介-慢性肺曲霉菌病感染

2014ESCMID曲霉菌病治療指南-慢性肺曲霉病2014ESCMIDAspergillusGuideline-ChronicPulmonaryAspergillosisPresentbyDavidW.Denning[UnitedKingdom]ECCMID10thMay2015inBarcelona)歐洲臨床微生物與感染性疾病學會(ESCMID,EuropeanSocietyofClinicalMicrobiologyandInfectiousDiseases)濱州醫(yī)學院附屬煙臺海港醫(yī)院急診科王功軍1精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona慢性肺曲霉菌病-疾病分類ChronicPulmonaryAspergillosis-subsets單發(fā)曲霉球Simple/singleAspergilloma曲霉肉芽腫病Aspergillusnodule(s)慢性空腔曲霉菌病/復雜曲霉球病ChronicCavitaryPulmonaryAspergillosis/ComplexAspergilloma(CCPA)慢性纖維化肺曲霉菌病ChronicFibrosingPulmonaryAspergillosis(CFPA)亞急性侵襲性/半侵襲性/慢性壞死性肺曲霉菌病Subacuteinvasive(SIA)/Semi-Invasive/ChronicNecrotizingPulmonaryAspergillosis(CNPA)注：真菌球（曲霉球）可出現(xiàn)在以上除曲霉菌肉芽腫之外的任意一種情況中–fungalballs(aspergilloma)maybeseeninanyoftheseconditions,exceptAspergillusnodule2精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona慢性曲霉菌病臨床表現(xiàn)分類ClinicalphenotypesofchronicAspergillussppdiseases單發(fā)曲霉球Single/simpleaspergilloma慢性壞死性/亞急性肺曲霉菌病Chronicnecrotizingpulmonaryaspergillosis(CNPA)orsubacuteInvasiveaspergillosis(SAI)慢性空腔性肺曲霉菌病Chroniccavitarypulmonaryaspergillosis(CCPA)慢性纖維化肺曲霉菌病Chronicfibrosingpulmonaryaspergillosis(CFPA)曲霉菌肉芽腫Aspergillusnodule(s)3精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona不同類型的慢性曲霉菌病DifferentpatternsofCPA曲霉菌肉芽腫Aspergillusnodule(s)單發(fā)曲霉球Single/simpleaspergilloma慢性空腔性肺曲霉菌病Chroniccavitarypulmonaryaspergillosis(CCPA)慢性纖維化肺曲霉菌病Chronicfibrosingpulmonaryaspergillosis(CFPA)4精選2021版課件慢性肺曲霉菌病-診斷標準ChronicPulmonaryAspergillosis–Diagnosticcriteria需要滿足以下條件：1.1CT影像學表現(xiàn)為肺部真菌球或胸腔內空腔，或支氣管擴張CharacteristicCTappearanceofafungusballinapulmonaryorpleuralcavity,ordilatedbronchus,+1.2任何與曲霉菌感染相關的直接或間接的微生物證據(jù)AnydirectorindirectmicrobiologicalevidenceofAspergillusinfection(seebelow).,或：2.1影像學特征持續(xù)表現(xiàn)為慢性肺曲霉菌?。ò涨?，胸膜增厚，嚴重的纖維化或肉芽腫）Radiologicalfeaturesconsistentwithchronicpulmonaryaspergillosis(includingcavity(ies),pleuralthickening,extensivefibrosisornodule)+2.2患者的臨床表現(xiàn)和影像學證據(jù)至少存在3個月以上時間[注意半侵襲性/慢性壞死性肺曲霉病的疾病療程相對CPA較短，可逐漸演化成慢性肺曲霉病]Clinicalorradiologicalevidenceofatleast3monthsdisease(sometimesinferred)[NoteshorterdurationsofdiseasemaybeseeninSIA/CNPA,whichbecomesCPAbecauseofitschronicity],+2.3獲得與曲霉菌感染相關的組織病理或微生物證據(jù)或免疫學證據(jù)（如：肺活檢中組織病理發(fā)現(xiàn)曲霉樣菌絲或經皮肺穿刺培養(yǎng)陽性；肺泡灌洗液抗原強陽性；IgG抗體陽性/曲霉沉淀素陽性）呼吸道分泌物培養(yǎng)或PCR方法檢測曲霉樣性HistologicalormicrobiologicalorimmunologicevidenceofAspergillusinfection(e.g.histologicalevidenceofAspergillus-likehyphaeinlungbiopsyorAspergillusculturefromapercutaneouscavityaspiration;stronglypositiveBALantigen;positiveIgGantibody/precipitins).RespiratorytractcultureorPCRpositiveforAspergillusissupportive.排除：對于特定地區(qū)或游歷該地區(qū)患者需要排除組織胞漿菌，球孢子菌和副球孢子菌感染；以及排除肺放線菌病。排除活動性細菌感染，包括分枝桿菌感染伴或不伴惡性腫瘤。分枝桿菌感染可能與真菌感染相似Exclusionofhistoplasmosis,coccidioidomycosisandparacoccidiodomycosisinendemicareasorthosewithpertinenttravelhistory;actinomycosis.Activebacterialinfection,includingmycobacterialinfectionand/ormalignancymayoccurconcurrently.MycobacterialinfectionsormalignancymaymimicCPA.PresentbyDavidDenningECCMID10thMay2015inBarcelona5精選2021版課件慢性肺曲霉菌病-氣道標本的診斷RespiratoryspecimendiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預手段InterventionSoRQoE文獻Reference備注Comment在非免疫抑制患者中伴有空腔/結節(jié)肺浸潤CavitaryornodularpulmonaryinfiltrateinNon-immunocompromisedpatients診斷或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPA確診或排除其他病原體TodocumentorExcludeotherpathogens直接鏡檢發(fā)現(xiàn)菌絲Directmicroscopyforhyphae組織病理Histology（氣道分泌物）真菌培養(yǎng)Fungalculture（respiratorysecretion）（經皮肺穿刺）真菌培養(yǎng)Fungalculture(transparietalaspiration)（氣道分泌物）曲霉菌PCRAspergillusPCR(respiratorysecretion)細菌培養(yǎng)BacterialcultureAAABCCIIIIIIIIIIIIItUffredi,2003Denning,2003;Horvath,1994Denning,2013;Duddy,2012Horvath,1994慢性曲霉菌病中病理能夠將半侵襲性曲霉菌?。⊿AIA）/慢性壞死性肺曲霉菌病與慢性空腔性肺曲霉菌病區(qū)分開來。鏡檢陽性是一個感染的強指證。細菌培養(yǎng)平板的敏感性叫真菌平板的敏感性較低。PCR的敏感性較培養(yǎng)高6精選2021版課件慢性肺曲霉菌病-抗原檢測AntigendiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預手段InterventionSoRQoE文獻Reference備注Comment在非免疫抑制患者中伴有空腔/結節(jié)肺浸潤CavitaryornodularpulmonaryinfiltrateinNon-immunocompromisedpatients診斷或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPA肺泡灌洗液抗原Antigen（BAL）血清學抗原檢測Antigen（Serum）痰培抗原檢測BCIIIIIzumikawa,2012Izumikawa,2012;Kono,2013;Shin,2014血清和肺泡灌洗液的抗原檢測已經建立研究，但痰液的抗原尚未涉及Antigen（Sputum）Nodata7精選2021版課件慢性肺曲霉菌病-抗體檢測AspergillusantibodydiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預手段InterventionSoRQoE文獻Reference備注Comment在非免疫抑制患者中伴有空腔/結節(jié)肺浸潤CavitaryornodularpulmonaryinfiltrateinNon-immunocompromisedpatients診斷或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPA曲霉抗體IgGAspergillusIgGantibodyAspergillusIgMantibodyAspergillusIgAantibodyAspergillusIgEantibodyAADDBIIIIIIIIIIIIGuitard,2012;Baxter,2012;VanToorenenbergen,2012BTS,1970;Uffredi,2003;Kitasato,2009;Ohba,2012;Baxter,2012Schonheyder1987;Nimomiya,1990;Denning,2003;Agarwal,2012IgG和曲霉沉淀素的標準建立尚未完成哮喘/變態(tài)反應性肺曲霉菌?。ˋBPA）/囊性纖維化(CF)Asthma/ABPA/CFAspergillusprecipitins曲霉沉淀素曲霉抗體IgM曲霉抗體IgA曲霉抗體IgEBrouwer,1988;多數(shù)室內測試尚未應用，主要原因是不確定的敏感性曲霉肉芽腫的敏感性尚不確定8精選2021版課件慢性肺曲霉菌病-影像學診斷和隨訪RadiologicaldiagnosisandfollowupofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預手段InterventionSoRQoE文獻Reference備注Comment以空腔，真菌球為特征，胸膜增厚伴/不伴上肺葉的纖維化Featuresofcavitation,fungalball,pleuralthickeningand/orupperlobefibrosis提高臨床醫(yī)師對慢性曲霉菌病的關注RaisesuspicionofCPAforphysicians影像報告必須提及慢性肺曲霉菌病的可能性RadiologicalreportmustMentionpossibleCPACTScan（contrast）AAIIII慢性曲霉菌常被長期誤診并未給予治療CPAisoftenmissedforyearsandpatientsmismanaged.微生物檢查結果需要具備血管成像高分辨CT的對照確認MicrobiologicaltestingrequiredforconfirmationHighqualityCTwithvesselvisualisation隨訪患者及停藥FollowuponorofftherapyCT掃描（對照）專家的影像方面的建議X胸片提示疑似慢性肺曲霉菌病SuspicionofchronicpulmonaryaspergillosisonCXR診斷或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPAPETscanPET掃描DIIICTScan（lowdosage）CT掃描（低劑量）CXRX胸片BIIIBIIIInitialFUat3-6mosandwithchangeofstatus初始抗真菌治療3-6個月并伴有狀態(tài)的改變AIIExpertradiologyadvice9精選2021版課件肺曲霉菌病侵襲性肺曲菌病的影像變化：Air-crescentsignD10-20HalosignD0-5Air-spaceconsolidationD5-1010精選2021版課件肺曲霉菌病發(fā)病初：兩周后：11精選2021版課件肺曲霉菌病肺曲菌病---多發(fā)小結節(jié)型12精選2021版課件肺曲霉菌病13精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona慢性肺曲霉菌表現(xiàn)為腔內曲霉球充滿空腔。胸膜的增厚，臨近軟組織空腔壁可能難以辨別。注意胸膜外脂肪組織的高衰減（如箭頭所示）14精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona所示為一位長期吸煙的慢性肺曲霉菌病患者。真菌球（藍色箭頭所示）幾乎填滿了肺氣腫所形成的肺大泡a)縱隔窗視角b）肺窗視角c-e）逐層掃描冠狀成形和X線胸片呈現(xiàn)進行性的增厚。注意因為感染炎性介質導致的右鎖骨下靜脈的差異。盡管冠狀面成形清晰的說明了病變，但從胸片影像的陰影上分析卻難得多15精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelonaabcdef一位有長期吸煙史，堪薩斯分枝桿菌感染，營養(yǎng)不良和肝硬化患者?；颊邤?shù)度咳血，在給予長期伏立康唑治療的同時給予動脈栓塞治療。雙側曲霉球幾乎填滿了整個空腔（a-d中星形標記）。注意（e-f）中左肺的小空腔和不規(guī)則空腔壁。相對于胸膜增厚（黃色箭頭標注）和肺泡實變（藍色箭頭標注），曲霉球表現(xiàn)為較弱地衰減。全身性動脈肥大（紅色箭頭標注）16精選2021版課件肺曲霉菌病曲菌球隨體位的變化：仰臥位胸部CT俯臥位胸部CT17精選2021版課件肺曲霉菌病曲菌球18精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona偽腫瘤表現(xiàn)的慢性肺曲霉病患者（手術確認）19精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預手段InterventionSoRQoE文獻Reference備注Comment慢性肺曲霉病進展期患者CPApatientswithprogressivedisease控制感染性疾病進展Controlofinfection伊曲康唑起始200mgBID，通過血藥濃度檢測調整劑量ItraconazoleStart200mgBID,adjustwithTDMAII無治療藥物對照研究數(shù)據(jù)慢性肺曲霉菌病-三唑類藥物治療OraltriazoletherapyforCPAPopulation伏立康唑起始150-250mgBID，通過血藥濃度檢測調整劑量VoriconazoleStart150-250mgBID,adjustwithTDMAII泊沙康唑起始400mgBIDPosaconazoleStart400mgBIDBII伏立康唑更適合用于半侵襲性曲霉菌?。⊿IA）/慢性壞死性肺曲霉菌?。–NPA）以及伴有真菌球的患者以減少耐藥的風險Agarwal,2013;DeBuele,1998,Dupont,1990;Campbell,1991;Tsubura,1997;Denning,2003;Nam,2009;Al-shair,2013Saito,2009;Cadranel,2012,Jain,2006;Sambatakou,2006;Camuset,2007;Philippe,2009;Al-shair,2013Felton,2010;應用伏立康唑，伊曲康唑時或權衡利弊使用泊沙康唑時需要血藥濃度檢測目標濃度來自于侵襲性曲霉菌病，PK/PD和預防研究數(shù)據(jù)20精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預手段InterventionSoRQoE文獻Reference備注Comment慢性肺曲霉病進展期患者（初始治療失敗，三唑類藥物不耐受，或三唑類藥物耐藥）CPApatientswithprogressivedisease,whofail,areintolerantoftriazolesorhavetriazoleresistance控制感染性疾病進展Controlofinfection米卡芬凈150mg/dItraconazoleStart200mgBID,adjustwithTDMBII慢性肺曲霉菌病-針劑替代治療AlternativeintravenoustherapyforCPA兩性霉素B0.7-1.0mg/kg/dAmphotericinBdeoxycholate0.7-1.0mg/kg/dCIII卡泊芬凈50-70mg/dCaspofungin50-70mg/dCIIaKohno,2011;Kohno,EJCMID2013;Saito,2009;Kohno,2011;Kohno,2004;Izumikawa,2007;Yasuda,2009;Nam,2009Denning,2003Kier,2014;KohnoECCMID2013兩性霉素B脂質體3mg/kg/dLiposomalAmB3mg/kg/dBIIaNewton,201421精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預手段InterventionSoRQoE文獻Reference備注Comment伴有曲霉球的慢性肺曲霉病患者，不愿意或不能給予口服治療，唑類藥物多耐藥以及不能手術治療患者CPAwithaspergilloma,unwillingorunabletotakeoraltherapy,multiazoleresistanceandinoperable控制感染性疾病進展Controlofinfection兩性霉素B腔內注射InstillationofamphotericinBDeoxycholateintocavityCII慢性肺曲霉菌病-局部空腔治療LocalcavitytherapyforCPAGiron,1998;Kravitz,2013實驗性治療22精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預手段InterventionSoRQoE文獻Reference備注Comment慢性肺曲霉病抗真菌治療CPApatientsonAntifungaltherapy控制感染性疾病進展，組織肺纖維化，預防出血，改善甚或質量Controlofinfection,arrestofpulmonaryFibrosis,preventionofHaemoptysis,improvedqualityoflife.6個月抗真菌治療6moantifungaltherapyBII治療慢性肺曲霉菌病的最佳療程尚未知曉；在部分患者中長期哦抑制治療可能是恰當?shù)穆苑吻咕?抗真菌治療療程DurationofantifungaltherapyforCPAAgarwal,2013:Yoshida,2012;Nam,2010:Felton,2010;Camuset,2007:Jain,2006:Cadranel,2012亞急性肺曲霉菌病/慢性壞死性肺曲霉菌病SubacuteIA/CNPA治愈Cure長療程抗真菌治療，療程取決于患者狀態(tài)和藥物耐受性LongtermantifungalTherapy,dependingonstatusanddrugtoleranceCII6個月6moBIIFelton,2010;Camuset,2007;Jain,2006;Cadranel,2012Camuset,2007Cadranel,2012OptimaldurationoftherapyinCPAisunknown,IndefinitesuppressivetherapymaybeAppropriateinselectedpatients23精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預手段InterventionSoRQoE文獻Reference備注Comment單個/簡單曲霉球病Simple/singleaspergilloma治愈病預防威脅生命的出血Cureandpreventionoflifethreateninghaemoptysis肺葉摘除或其他局部切除LobectomyoranyothersegmentalresectionAII患者需要嚴格的手風險評估：手術評估=風險/獲益慢性肺曲霉菌病-手術指證IndicationsforsurgeryinCPADaly,1986;Regnard,2000;Kim,2005;Pratap,2007;Brik,2008;Muniappan,2014;Farid,2013;Chen,2012;Nacera,2012;Lejay,2011;IDSA2008圖像引導下胸腔鏡手術（VATS）Video-assistedthoracicsurgery(VATS)BIIChen,2014;Muniappan,2014.抗真菌治療下慢性空腔性肺曲霉菌病復發(fā)（包括多重三唑類耐藥），伴有/不伴威脅生命的出血CCPArefractorytomedicalmanagement(includingmulti-azoleresistance)withantifungaltreatmentand/orlife-threateninghaemoptysis.改善疾病的控制，可能治愈