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1、肺曲霉菌病诊疗肺曲霉菌病诊疗肺曲霉菌病肺曲霉菌病发病率呈上升趋势发病率呈上升趋势北京协和医院2003年报道IFI发病率是90年代的3.6倍国内临床研究：HSCT患者IFI发病率14%25%1美国尸检研究：异体HSCT患者IFI发生率31%，粒缺患者44%2ICU IFI占医院获得性感染的815%3器官移植后IFI发病率约21%1.Liu ZY,et al.Chin Med J 2003,83,(5):399-402.3.Chin J Intem Med,2007,46(11):960-966.2.Haematologica.2006 Jul;91(7):986-9.肺曲霉菌病肺曲霉菌病致病菌分
2、布致病菌分布 移植后发生IFI的患者中念珠菌和曲霉感染占80%血液科侵袭性曲霉感染者较多，发病率40%左右 ICU约90%为念珠菌感染，其中白念占40%60%非白念（光滑念、热带念、近平滑念、克柔念等）比例在逐渐增加血症血症曲菌分类 超过185种 约有20种可导致机会性感染A.fumigatusA.fumigatus烟曲霉（烟曲霉（70%70%）A.flavusA.flavus黄曲霉（黄曲霉（20%20%）A.nigerA.niger黑曲霉（低于黑曲霉（低于10%10%）A.clavatus棒曲霉 A.glaucus灰绿曲霉 A.nidulans构巢曲霉 A.oryzae米曲霉 A.terre
3、us土曲霉A.ustus焦曲霉A.versicolor花斑曲霉1、烟曲霉菌、烟曲霉菌 在在SDA培养基上菌落生长快，棉花培养基上菌落生长快，棉花样，开始为白色，样，开始为白色，2 3天后转为天后转为绿绿色，数日后变为深绿色，色，数日后变为深绿色，呈粉末呈粉末状。状。分生孢子头的顶囊烧瓶状，小分生孢子头的顶囊烧瓶状，小梗单层，排列成木栅状，布满顶囊梗单层，排列成木栅状，布满顶囊表面表面3/4，顶端有链形分生孢子，分顶端有链形分生孢子，分生孢子球形，有小棘，绿色生孢子球形，有小棘，绿色 分生孢子分生孢子2、黄曲霉菌、黄曲霉菌 在SDA培养基上菌落生长快，黄色，表面粉末状。分生孢子头顶囊球形或近球形
4、，小梗双层，第一层长，布满顶囊表面，呈放射状排列，黄色，顶端有链形孢子 3、土曲霉菌、土曲霉菌在在SDA培养基上菌落生长快，小，培养基上菌落生长快，小，圆形，淡褐色或褐色。圆形，淡褐色或褐色。分生孢子头分生孢子头的顶囊半球形，小梗双层，第一层的顶囊半球形，小梗双层，第一层短，第二层长短，第二层长，呈放射状排列，呈放射状排列，分分布顶囊表面布顶囊表面2/3，顶端有链形孢子顶端有链形孢子 肿/瘤侵袭性肺部曲菌感染的困惑侵袭性肺部曲菌感染的困惑 不同地区、不同医疗环境发病率相同吗不同地区、不同医疗环境发病率相同吗?没有病理证据的下如何确诊？没有病理证据的下如何确诊？非肿瘤患者肺曲菌感染临床特点？非肿
5、瘤患者肺曲菌感染临床特点？抗曲菌经验治疗（升阶梯还是降阶梯？）抗曲菌经验治疗（升阶梯还是降阶梯？）非肿瘤患者肺曲菌感染疗程如何？非肿瘤患者肺曲菌感染疗程如何？肺曲霉菌感染的定位？首位？肺曲霉菌感染的定位？首位？2011.9卫生部专家培训卫生部专家培训+结合病原全程靶向possible-probable-proven-confirm广谱抗菌抗优势菌河北省河北省306306例非肿瘤患者侵袭性肺部真菌例非肿瘤患者侵袭性肺部真菌感染病原分布感染病原分布21.1%43.2%阎锡新、齐天杰，杨丛丽等，阎锡新、齐天杰，杨丛丽等，中华医院感染杂志，中华医院感染杂志，2012，1）刘又宁报告肺曲霉菌感染影像学特
6、点刘又宁报告肺曲霉菌感染影像学特点 河北省河北省306306例侵袭性肺部真菌影像学特点例侵袭性肺部真菌影像学特点n所入选各病例多有以下改变的所入选各病例多有以下改变的2-3种，甚至达种，甚至达5种之多种之多其中其中50例为例为曲霉菌感染曲霉菌感染曲霉菌形成空洞性病变曲霉菌形成空洞性病变70.4%，但只有，但只有4例患者形成了典型的例患者形成了典型的“晕轮征晕轮征”或或“空气半月征空气半月征”；念珠菌有；念珠菌有14.4%伴空洞，未见伴空洞，未见“晕轮征晕轮征”。肺部曲菌病常见临床类型n腐生曲菌病(曲菌球)n过敏性支气管肺曲菌病n肺侵袭性曲菌病(IPA)(acute tracheo-bronch
7、itis,bronchiolitis(毛细支气管炎),bronchopneumonia,obstructing bronchopulmonary aspergillosis)n血管侵袭性曲菌病2008 IDSA指南引述依据之一Angioinvasive aspergillosis42-42 year-old man with acute myelogenous leukemia 髓性白血病：halo of ground-glass attenuation 晕轮征pulmonary infarctionvascular invasionSaprophytic aspergillosis(aspe
8、rgilloma)腐生性曲菌病(曲霉肿)54-year-old man with a54-year-old man with a history of tuberculosis.(a)Linear tomogram(magnified view)shows multiple fungus balls within a cavity in the right upper lobe.(b)Photograph of the corresponding gross surgical specimen demonstrates multiple irregular fungus balls virtu
9、ally filling the pulmonary cavity.腐生性曲菌病(曲霉肿)air crescent sign空气新月征71-year-old man with residual tuberculosis.Chest computed tomographic(CT)scan(lung window)shows large cavities bilaterally in the upper lobes containing fungus balls of different sizes.Allergic bronchopulmonary aspergillosis7-14%激素依赖
10、型哮喘为ABPA43-year-old asthmatic man.(a,b)Thin-section CT scans show multiple tubular areas of increased attenuation.(c)Photomicrograph demonstrate mucous plugs composed of mucin(d)Photomicrograph Grocot silverstain)clearly shows multiple fungal hyphae.菌丝 Chronic Necrotizing AspergillosisSemi-invasive
11、aspergillosis in a 68-year-old man with chronic bronchitis and recurrent episodes of mild hemoptysis.(a)Thin-section CT scan(lung window)shows bilateral rounded areas of consolidation with associated cavitation in both upper lobes.(b)Photograph of an autopsy specimen from the left upper lobe shows a
12、n irregular cavitary lesion with regular margins and a dark brown appearance caused by necrotic material and Aspergillus infection.Necrotizing bronchial aspergillosis 54-year-old man who presented with cough and sputum production.(a)Chest CT scan(mediastinal window)obtained at the level of the carin
13、a shows a thickened,narrowed right main bronchus with associated right upper lobe collapse.(b)Bronchoscopic image shows elevated,whitish mucosal lesions in the right main bronchus(arrow).(c)High-power photomicrograph(original magnification,400;hematoxylineosin stain)of a biopsy specimen from the rig
14、ht upper lobe reveals massive Aspergillus hyphae invading the bronchial epithelium。Airway-invasive AspergillosisInvasive bronchiolar aspergillosis in a patient who had undergone bone marrowtransplantation.(a)Thin-section CT scan(lung window)shows peripheral branchingstructures associated with focal
15、areas of consolidation in the right lower lobe.(b)Photograph of the corresponding autopsy specimen shows multiple yellowish acinar nodules.(c)High-power photomicrograph of a lung biopsy specimen demonstrates complete destruction of the bronchiolar wall by Aspergillus infection.支气管壁被曲菌完全破坏02468101214
16、195019601970198019902000制霉菌素两性霉素B(1958)灰黄霉素5-FC咪康唑酮康唑氟康唑伊曲康唑 L-AmB ABCD ABLC特比萘芬粪壳菌素伏立康唑泊沙康唑XMP卡泊芬净米卡芬净雷夫康唑阿尼芬净药物数量肺曲霉菌感染治疗肺曲霉菌感染治疗-抗真菌药物与治疗指南AFVariableFavorable response%（n/N）Overall总体56.4Probable aspergillosis疑诊56.3Proven aspergillosis确诊56.7Combination therapy单药56.3Monotherapy联合56.5First-line therapy一线治疗60.0Salvage therapy挽救治疗55.6Neutropenic status at start of caspofungin therapy(ANC6432820.50.120.03土曲霉土曲霉（50）烟曲霉烟曲霉（100）黄曲霉黄曲霉（50）曲霉菌属曲霉菌属 spp0.015（g/mL）0.060.251416646432820.50.120.03黑曲霉黑曲霉（50）
