ECCMID-曲霉菌指南簡(jiǎn)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(xué)會(huì)(ESCMID,EuropeanSocietyofClinicalMicrobiologyandInfectiousDiseases)濱州醫(yī)學(xué)院附屬煙臺(tái)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(lèi)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(fù)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(lèi)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(lèi)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(biāo)準(zhǔn)ChronicPulmonaryAspergillosis–Diagnosticcriteria需要滿(mǎn)足以下條件：1.1CT影像學(xué)表現(xiàn)為肺部真菌球或胸腔內(nèi)空腔，或支氣管擴(kuò)張CharacteristicCTappearanceofafungusballinapulmonaryorpleuralcavity,ordilatedbronchus,+1.2任何與曲霉菌感染相關(guān)的直接或間接的微生物證據(jù)AnydirectorindirectmicrobiologicalevidenceofAspergillusinfection(seebelow).,或：2.1影像學(xué)特征持續(xù)表現(xiàn)為慢性肺曲霉菌病（包括空腔，胸膜增厚，嚴(yán)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(xué)證據(jù)至少存在3個(gè)月以上時(shí)間[注意半侵襲性/慢性壞死性肺曲霉病的疾病療程相對(duì)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(guān)的組織病理或微生物證據(jù)或免疫學(xué)證據(jù)（如：肺活檢中組織病理發(fā)現(xiàn)曲霉樣菌絲或經(jīng)皮肺穿刺培養(yǎng)陽(yáng)性；肺泡灌洗液抗原強(qiáng)陽(yáng)性；IgG抗體陽(yáng)性/曲霉沉淀素陽(yáng)性）呼吸道分泌物培養(yǎng)或PCR方法檢測(cè)曲霉樣性HistologicalormicrobiologicalorimmunologicevidenceofAspergillusinfection(e.g.histologicalevidenceofAspergillus-likehyphaeinlungbiopsyorAspergillusculturefromapercutaneouscavityaspiration;stronglypositiveBALantigen;positiveIgGantibody/precipitins).RespiratorytractcultureorPCRpositiveforAspergillusissupportive.排除：對(duì)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(xiàn)菌病。排除活動(dòng)性細(xì)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(biāo)本的診斷RespiratoryspecimendiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預(yù)手段InterventionSoRQoE文獻(xiàn)Reference備注Comment在非免疫抑制患者中伴有空腔/結(jié)節(jié)肺浸潤(rùn)C(jī)avitaryornodularpulmonaryinfiltrateinNon-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(jīng)皮肺穿刺）真菌培養(yǎng)Fungalculture(transparietalaspiration)（氣道分泌物）曲霉菌PCRAspergillusPCR(respiratorysecretion)細(xì)菌培養(yǎng)BacterialcultureAAABCCIIIIIIIIIIIIItUffredi,2003Denning,2003;Horvath,1994Denning,2013;Duddy,2012Horvath,1994慢性曲霉菌病中病理能夠?qū)肭忠u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(kāi)來(lái)。鏡檢陽(yáng)性是一個(gè)感染的強(qiáng)指證。細(xì)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(cè)AntigendiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預(yù)手段InterventionSoRQoE文獻(xiàn)Reference備注Comment在非免疫抑制患者中伴有空腔/結(jié)節(jié)肺浸潤(rùn)C(jī)avitaryornodularpulmonaryinfiltrateinNon-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(xué)抗原檢測(cè)Antigen（Serum）痰培抗原檢測(cè)BCIIIIIzumikawa,2012Izumikawa,2012;Kono,2013;Shin,2014血清和肺泡灌洗液的抗原檢測(cè)已經(jīng)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(cè)AspergillusantibodydiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預(yù)手段InterventionSoRQoE文獻(xiàn)Reference備注Comment在非免疫抑制患者中伴有空腔/結(jié)節(jié)肺浸潤(rùn)C(jī)avitaryornodularpulmonaryinfiltrateinNon-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(biāo)準(zhǔn)建立尚未完成哮喘/變態(tài)反應(yīng)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(nèi)測(cè)試尚未應(yīng)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(xué)診斷和隨訪(fǎng)RadiologicaldiagnosisandfollowupofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預(yù)手段InterventionSoRQoE文獻(xiàn)Reference備注Comment以空腔，真菌球?yàn)樘卣鳎啬ぴ龊癜?不伴上肺葉的纖維化Featuresofcavitation,fungalball,pleuralthickeningand/orupperlobefibrosis提高臨床醫(yī)師對(duì)慢性曲霉菌病的關(guān)注RaisesuspicionofCPAforphysicians影像報(bào)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(zhǎng)期誤診并未給予治療CPAisoftenmissedforyearsandpatientsmismanaged.微生物檢查結(jié)果需要具備血管成像高分辨CT的對(duì)照確認(rèn)MicrobiologicaltestingrequiredforconfirmationHighqualityCTwithvesselvisualisation隨訪(fǎng)患者及停藥FollowuponorofftherapyCT掃描（對(duì)照）專(zhuān)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(gè)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(jié)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(nèi)曲霉球充滿(mǎn)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(zhǎng)期吸煙的慢性肺曲霉菌病患者。真菌球（藍(lán)色箭頭所示）幾乎填滿(mǎn)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(xiàn)胸片呈現(xiàn)進(jìn)行性的增厚。注意因?yàn)楦腥狙仔越橘|(zhì)導(dǎo)致的右鎖骨下靜脈的差異。盡管冠狀面成形清晰的說(shuō)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(zhǎng)期吸煙史，堪薩斯分枝桿菌感染，營(yíng)養(yǎng)不良和肝硬化患者?；颊邤?shù)度咳血，在給予長(zhǎng)期伏立康唑治療的同時(shí)給予動(dòng)脈栓塞治療。雙側(cè)曲霉球幾乎填滿(mǎn)了整個(gè)空腔（a-d中星形標(biāo)記）。注意（e-f）中左肺的小空腔和不規(guī)則空腔壁。相對(duì)于胸膜增厚（黃色箭頭標(biāo)注）和肺泡實(shí)變（藍(lán)色箭頭標(biāo)注），曲霉球表現(xiàn)為較弱地衰減。全身性動(dòng)脈肥大（紅色箭頭標(biāo)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(shù)確認(rèn)）19精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預(yù)手段InterventionSoRQoE文獻(xiàn)Reference備注Comment慢性肺曲霉病進(jìn)展期患者CPApatientswithprogressivedisease控制感染性疾病進(jìn)展Controlofinfection伊曲康唑起始200mgBID，通過(guò)血藥濃度檢測(cè)調(diào)整劑量ItraconazoleStart200mgBID,adjustwithTDMAII無(wú)治療藥物對(duì)照研究數(shù)據(jù)慢性肺曲霉菌病-三唑類(lèi)藥物治療OraltriazoletherapyforCPAPopulation伏立康唑起始150-250mgBID，通過(guò)血藥濃度檢測(cè)調(diào)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(fēng)險(xiǎn)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(yīng)用伏立康唑，伊曲康唑時(shí)或權(quán)衡利弊使用泊沙康唑時(shí)需要血藥濃度檢測(cè)目標(biāo)濃度來(lái)自于侵襲性曲霉菌病，PK/PD和預(yù)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(yù)手段InterventionSoRQoE文獻(xiàn)Reference備注Comment慢性肺曲霉病進(jìn)展期患者（初始治療失敗，三唑類(lèi)藥物不耐受，或三唑類(lèi)藥物耐藥）CPApatientswithprogressivedisease,whofail,areintolerantoftriazolesorhavetriazoleresistance控制感染性疾病進(jìn)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(zhì)體3mg/kg/dLiposomalAmB3mg/kg/dBIIaNewton,201421精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預(yù)手段InterventionSoRQoE文獻(xiàn)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(lèi)藥物多耐藥以及不能手術(shù)治療患者CPAwithaspergilloma,unwillingorunabletotakeoraltherapy,multiazoleresistanceandinoperable控制感染性疾病進(jìn)展Controlofinfection兩性霉素B腔內(nèi)注射InstillationofamphotericinBDeoxycholateintocavityCII慢性肺曲霉菌病-局部空腔治療LocalcavitytherapyforCPAGiron,1998;Kravitz,2013實(shí)驗(yàn)性治療22精選2021版課件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干預(yù)手段InterventionSoRQoE文獻(xiàn)Reference備注Comment慢性肺曲霉病抗真菌治療CPApatientsonAntifungaltherapy控制感染性疾病進(jìn)展，組織肺纖維化，預(yù)防出血，改善甚或質(zhì)量Controlofinfection,arrestofpulmonaryFibrosis,preventionofHaemoptysis,improvedqualityoflife.6個(gè)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(zhǎng)期哦抑制治療可能是恰當(dāng)?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(zhǎng)療程抗真菌治療，療程取決于患者狀態(tài)和藥物耐受性L(fǎng)ongtermantifungalTherapy,dependingonstatusanddrugtoleranceCII6個(gè)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(yù)手段InterventionSoRQoE文獻(xiàn)Reference備注Comment單個(gè)/簡(jiǎn)單曲霉球病Simple/singleaspergilloma治愈病預(yù)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(yán)格的手風(fēng)險(xiǎn)評(píng)估：手術(shù)評(píng)估=風(fēng)險(xiǎn)/獲益慢性肺曲霉菌病-手術(shù)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(dǎo)下胸腔鏡手術(shù)（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(fù)發(fā)（包括多重三唑類(lèi)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