ECCMID-曲霉菌指南简介-慢性肺曲霉菌病感染

2014ESCMID曲霉菌病治疗指南-慢性肺曲霉病2014ESCMIDAspergillusGuideline-ChronicPulmonaryAspergillosisPresentbyDavidW.Denning[UnitedKingdom]ECCMID10thMay2015inBarcelona)欧洲临床微生物与感染性疾病学会(ESCMID,EuropeanSocietyofClinicalMicrobiologyandInfectiousDiseases)滨州医学院附属烟台海港医院急诊科王功军1精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona慢性肺曲霉菌病-疾病分类ChronicPulmonaryAspergillosis-subsets单发曲霉球Simple/singleAspergilloma曲霉肉芽肿病Aspergillusnodule(s)慢性空腔曲霉菌病/复杂曲霉球病ChronicCavitaryPulmonaryAspergillosis/ComplexAspergilloma(CCPA)慢性纤维化肺曲霉菌病ChronicFibrosingPulmonaryAspergillosis(CFPA)亚急性侵袭性/半侵袭性/慢性坏死性肺曲霉菌病Subacuteinvasive(SIA)/Semi-Invasive/ChronicNecrotizingPulmonaryAspergillosis(CNPA)注：真菌球（曲霉球）可出现在以上除曲霉菌肉芽肿之外的任意一种情况中–fungalballs(aspergilloma)maybeseeninanyoftheseconditions,exceptAspergillusnodule2精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona慢性曲霉菌病临床表现分类ClinicalphenotypesofchronicAspergillussppdiseases单发曲霉球Single/simpleaspergilloma慢性坏死性/亚急性肺曲霉菌病Chronicnecrotizingpulmonaryaspergillosis(CNPA)orsubacuteInvasiveaspergillosis(SAI)慢性空腔性肺曲霉菌病Chroniccavitarypulmonaryaspergillosis(CCPA)慢性纤维化肺曲霉菌病Chronicfibrosingpulmonaryaspergillosis(CFPA)曲霉菌肉芽肿Aspergillusnodule(s)3精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona不同类型的慢性曲霉菌病DifferentpatternsofCPA曲霉菌肉芽肿Aspergillusnodule(s)单发曲霉球Single/simpleaspergilloma慢性空腔性肺曲霉菌病Chroniccavitarypulmonaryaspergillosis(CCPA)慢性纤维化肺曲霉菌病Chronicfibrosingpulmonaryaspergillosis(CFPA)4精选2021版课件慢性肺曲霉菌病-诊断标准ChronicPulmonaryAspergillosis–Diagnosticcriteria需要满足以下条件：1.1CT影像学表现为肺部真菌球或胸腔内空腔，或支气管扩张CharacteristicCTappearanceofafungusballinapulmonaryorpleuralcavity,ordilatedbronchus,+1.2任何与曲霉菌感染相关的直接或间接的微生物证据AnydirectorindirectmicrobiologicalevidenceofAspergillusinfection(seebelow).,或：2.1影像学特征持续表现为慢性肺曲霉菌病（包括空腔，胸膜增厚，严重的纤维化或肉芽肿）Radiologicalfeaturesconsistentwithchronicpulmonaryaspergillosis(includingcavity(ies),pleuralthickening,extensivefibrosisornodule)+2.2患者的临床表现和影像学证据至少存在3个月以上时间[注意半侵袭性/慢性坏死性肺曲霉病的疾病疗程相对CPA较短，可逐渐演化成慢性肺曲霉病]Clinicalorradiologicalevidenceofatleast3monthsdisease(sometimesinferred)[NoteshorterdurationsofdiseasemaybeseeninSIA/CNPA,whichbecomesCPAbecauseofitschronicity],+2.3获得与曲霉菌感染相关的组织病理或微生物证据或免疫学证据（如：肺活检中组织病理发现曲霉样菌丝或经皮肺穿刺培养阳性；肺泡灌洗液抗原强阳性；IgG抗体阳性/曲霉沉淀素阳性）呼吸道分泌物培养或PCR方法检测曲霉样性HistologicalormicrobiologicalorimmunologicevidenceofAspergillusinfection(e.g.histologicalevidenceofAspergillus-likehyphaeinlungbiopsyorAspergillusculturefromapercutaneouscavityaspiration;stronglypositiveBALantigen;positiveIgGantibody/precipitins).RespiratorytractcultureorPCRpositiveforAspergillusissupportive.排除：对于特定地区或游历该地区患者需要排除组织胞浆菌，球孢子菌和副球孢子菌感染；以及排除肺放线菌病。排除活动性细菌感染，包括分枝杆菌感染伴或不伴恶性肿瘤。分枝杆菌感染可能与真菌感染相似Exclusionofhistoplasmosis,coccidioidomycosisandparacoccidiodomycosisinendemicareasorthosewithpertinenttravelhistory;actinomycosis.Activebacterialinfection,includingmycobacterialinfectionand/ormalignancymayoccurconcurrently.MycobacterialinfectionsormalignancymaymimicCPA.PresentbyDavidDenningECCMID10thMay2015inBarcelona5精选2021版课件慢性肺曲霉菌病-气道标本的诊断RespiratoryspecimendiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment在非免疫抑制患者中伴有空腔/结节肺浸润CavitaryornodularpulmonaryinfiltrateinNon-immunocompromisedpatients诊断或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPA确诊或排除其他病原体TodocumentorExcludeotherpathogens直接镜检发现菌丝Directmicroscopyforhyphae组织病理Histology（气道分泌物）真菌培养Fungalculture（respiratorysecretion）（经皮肺穿刺）真菌培养Fungalculture(transparietalaspiration)（气道分泌物）曲霉菌PCRAspergillusPCR(respiratorysecretion)细菌培养BacterialcultureAAABCCIIIIIIIIIIIIItUffredi,2003Denning,2003;Horvath,1994Denning,2013;Duddy,2012Horvath,1994慢性曲霉菌病中病理能够将半侵袭性曲霉菌病（SAIA）/慢性坏死性肺曲霉菌病与慢性空腔性肺曲霉菌病区分开来。镜检阳性是一个感染的强指证。细菌培养平板的敏感性叫真菌平板的敏感性较低。PCR的敏感性较培养高6精选2021版课件慢性肺曲霉菌病-抗原检测AntigendiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment在非免疫抑制患者中伴有空腔/结节肺浸润CavitaryornodularpulmonaryinfiltrateinNon-immunocompromisedpatients诊断或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPA肺泡灌洗液抗原Antigen（BAL）血清学抗原检测Antigen（Serum）痰培抗原检测BCIIIIIzumikawa,2012Izumikawa,2012;Kono,2013;Shin,2014血清和肺泡灌洗液的抗原检测已经建立研究，但痰液的抗原尚未涉及Antigen（Sputum）Nodata7精选2021版课件慢性肺曲霉菌病-抗体检测AspergillusantibodydiagnosisofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment在非免疫抑制患者中伴有空腔/结节肺浸润CavitaryornodularpulmonaryinfiltrateinNon-immunocompromisedpatients诊断或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPA曲霉抗体IgGAspergillusIgGantibodyAspergillusIgMantibodyAspergillusIgAantibodyAspergillusIgEantibodyAADDBIIIIIIIIIIIIGuitard,2012;Baxter,2012;VanToorenenbergen,2012BTS,1970;Uffredi,2003;Kitasato,2009;Ohba,2012;Baxter,2012Schonheyder1987;Nimomiya,1990;Denning,2003;Agarwal,2012IgG和曲霉沉淀素的标准建立尚未完成哮喘/变态反应性肺曲霉菌病（ABPA）/囊性纤维化(CF)Asthma/ABPA/CFAspergillusprecipitins曲霉沉淀素曲霉抗体IgM曲霉抗体IgA曲霉抗体IgEBrouwer,1988;多数室内测试尚未应用，主要原因是不确定的敏感性曲霉肉芽肿的敏感性尚不确定8精选2021版课件慢性肺曲霉菌病-影像学诊断和随访RadiologicaldiagnosisandfollowupofCPAPresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment以空腔，真菌球为特征，胸膜增厚伴/不伴上肺叶的纤维化Featuresofcavitation,fungalball,pleuralthickeningand/orupperlobefibrosis提高临床医师对慢性曲霉菌病的关注RaisesuspicionofCPAforphysicians影像报告必须提及慢性肺曲霉菌病的可能性RadiologicalreportmustMentionpossibleCPACTScan（contrast）AAIIII慢性曲霉菌常被长期误诊并未给予治疗CPAisoftenmissedforyearsandpatientsmismanaged.微生物检查结果需要具备血管成像高分辨CT的对照确认MicrobiologicaltestingrequiredforconfirmationHighqualityCTwithvesselvisualisation随访患者及停药FollowuponorofftherapyCT扫描（对照）专家的影像方面的建议X胸片提示疑似慢性肺曲霉菌病SuspicionofchronicpulmonaryaspergillosisonCXR诊断或排除慢性肺曲霉菌病DiagnosisOrexclusionofCPAPETscanPET扫描DIIICTScan（lowdosage）CT扫描（低剂量）CXRX胸片BIIIBIIIInitialFUat3-6mosandwithchangeofstatus初始抗真菌治疗3-6个月并伴有状态的改变AIIExpertradiologyadvice9精选2021版课件肺曲霉菌病侵袭性肺曲菌病的影像变化：Air-crescentsignD10-20HalosignD0-5Air-spaceconsolidationD5-1010精选2021版课件肺曲霉菌病发病初：两周后：11精选2021版课件肺曲霉菌病肺曲菌病---多发小结节型12精选2021版课件肺曲霉菌病13精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona慢性肺曲霉菌表现为腔内曲霉球充满空腔。胸膜的增厚，临近软组织空腔壁可能难以辨别。注意胸膜外脂肪组织的高衰减（如箭头所示）14精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona所示为一位长期吸烟的慢性肺曲霉菌病患者。真菌球（蓝色箭头所示）几乎填满了肺气肿所形成的肺大泡a)纵隔窗视角b）肺窗视角c-e）逐层扫描冠状成形和X线胸片呈现进行性的增厚。注意因为感染炎性介质导致的右锁骨下静脉的差异。尽管冠状面成形清晰的说明了病变，但从胸片影像的阴影上分析却难得多15精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelonaabcdef一位有长期吸烟史，堪萨斯分枝杆菌感染，营养不良和肝硬化患者。患者数度咳血，在给予长期伏立康唑治疗的同时给予动脉栓塞治疗。双侧曲霉球几乎填满了整个空腔（a-d中星形标记）。注意（e-f）中左肺的小空腔和不规则空腔壁。相对于胸膜增厚（黄色箭头标注）和肺泡实变（蓝色箭头标注），曲霉球表现为较弱地衰减。全身性动脉肥大（红色箭头标注）16精选2021版课件肺曲霉菌病曲菌球随体位的变化：仰卧位胸部CT俯卧位胸部CT17精选2021版课件肺曲霉菌病曲菌球18精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona伪肿瘤表现的慢性肺曲霉病患者（手术确认）19精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment慢性肺曲霉病进展期患者CPApatientswithprogressivedisease控制感染性疾病进展Controlofinfection伊曲康唑起始200mgBID，通过血药浓度检测调整剂量ItraconazoleStart200mgBID,adjustwithTDMAII无治疗药物对照研究数据慢性肺曲霉菌病-三唑类药物治疗OraltriazoletherapyforCPAPopulation伏立康唑起始150-250mgBID，通过血药浓度检测调整剂量VoriconazoleStart150-250mgBID,adjustwithTDMAII泊沙康唑起始400mgBIDPosaconazoleStart400mgBIDBII伏立康唑更适合用于半侵袭性曲霉菌病（SIA）/慢性坏死性肺曲霉菌病（CNPA）以及伴有真菌球的患者以减少耐药的风险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;应用伏立康唑，伊曲康唑时或权衡利弊使用泊沙康唑时需要血药浓度检测目标浓度来自于侵袭性曲霉菌病，PK/PD和预防研究数据20精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment慢性肺曲霉病进展期患者（初始治疗失败，三唑类药物不耐受，或三唑类药物耐药）CPApatientswithprogressivedisease,whofail,areintolerantoftriazolesorhavetriazoleresistance控制感染性疾病进展Controlofinfection米卡芬净150mg/dItraconazoleStart200mgBID,adjustwithTDMBII慢性肺曲霉菌病-针剂替代治疗AlternativeintravenoustherapyforCPA两性霉素B0.7-1.0mg/kg/dAmphotericinBdeoxycholate0.7-1.0mg/kg/dCIII卡泊芬净50-70mg/dCaspofungin50-70mg/dCIIaKohno,2011;Kohno,EJCMID2013;Saito,2009;Kohno,2011;Kohno,2004;Izumikawa,2007;Yasuda,2009;Nam,2009Denning,2003Kier,2014;KohnoECCMID2013两性霉素B脂质体3mg/kg/dLiposomalAmB3mg/kg/dBIIaNewton,201421精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment伴有曲霉球的慢性肺曲霉病患者，不愿意或不能给予口服治疗，唑类药物多耐药以及不能手术治疗患者CPAwithaspergilloma,unwillingorunabletotakeoraltherapy,multiazoleresistanceandinoperable控制感染性疾病进展Controlofinfection两性霉素B腔内注射InstillationofamphotericinBDeoxycholateintocavityCII慢性肺曲霉菌病-局部空腔治疗LocalcavitytherapyforCPAGiron,1998;Kravitz,2013实验性治疗22精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment慢性肺曲霉病抗真菌治疗CPApatientsonAntifungaltherapy控制感染性疾病进展，组织肺纤维化，预防出血，改善甚或质量Controlofinfection,arrestofpulmonaryFibrosis,preventionofHaemoptysis,improvedqualityoflife.6个月抗真菌治疗6moantifungaltherapyBII治疗慢性肺曲霉菌病的最佳疗程尚未知晓；在部分患者中长期哦抑制治疗可能是恰当的慢性肺曲霉菌病-抗真菌治疗疗程DurationofantifungaltherapyforCPAAgarwal,2013:Yoshida,2012;Nam,2010:Felton,2010;Camuset,2007:Jain,2006:Cadranel,2012亚急性肺曲霉菌病/慢性坏死性肺曲霉菌病SubacuteIA/CNPA治愈Cure长疗程抗真菌治疗，疗程取决于患者状态和药物耐受性LongtermantifungalTherapy,dependingonstatusanddrugtoleranceCII6个月6moBIIFelton,2010;Camuset,2007;Jain,2006;Cadranel,2012Camuset,2007Cadranel,2012OptimaldurationoftherapyinCPAisunknown,IndefinitesuppressivetherapymaybeAppropriateinselectedpatients23精选2021版课件PresentbyDavidDenningECCMID10thMay2015inBarcelona患者人群Population目的Intention干预手段InterventionSoRQoE文献Reference备注Comment单个/简单曲霉球病Simple/singleaspergilloma治愈病预防威胁生命的出血Cureandpreventionoflifethreateninghaemoptysis肺叶摘除或其他局部切除LobectomyoranyothersegmentalresectionAII患者需要严格的手风险评估：手术评估=风险/获益慢性肺曲霉菌病-手术指证IndicationsforsurgeryinCPADaly,1986;Regnard,2000;Kim,2005;Pratap,2007;Brik,2008;Muniappan,2014;Farid,2013;Chen,2012;Nacera,2012;Lejay,2011;IDSA2008图像引导下胸腔镜手术（VATS）Video-assistedthoracicsurgery(VATS)BIIChen,2014;Muniappan,2014.抗真菌治疗下慢性空腔性肺曲霉菌病复发（包括多重三唑类耐药），伴有/不伴威胁生命的出血CCPArefractorytomedicalmanagement(includingmulti-azoleresistance)withantifungaltreatmentand/orlife-threateninghaemoptysis.改善疾病的控制，可能治愈