University of Cologne, Faculty of Medicine, Department I for Internal Medicine, European Diamond Excellence Centre for Medical Mycology, University Hospital of Cologne, Cologne, Germany; University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Cologne, Germany.
Infectious Diseases Clinic, Department of Medicine University of Udine and Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy.
Clin Microbiol Infect. 2019 Dec;25(12):1501-1509. doi: 10.1016/j.cmi.2019.04.031. Epub 2019 May 16.
Severe pulmonary infections are among the most common reasons for admission to intensive care units (ICU). Within the last decade, increasing reports of severe influenza pneumonia resulting in acute respiratory distress syndrome (ARDS) complicated by Aspergillus infection were published.
To provide a comprehensive review of management of influenza-associated pulmonary aspergillosis in patients with ARDS.
Review of the literature pertaining to severe influenza-associated pulmonary aspergillosis. PubMed database was searched for publications from the database inception to January 2019.
In patients with lower respiratory symptoms, development of respiratory insufficiency should trigger rapid and thorough clinical evaluation, in particular in cases of suspected ARDS, including electrocardiography and echocardiography to exclude cardiac dysfunction, arrhythmias and ischaemia. Bronchoalveolar lavage should obtain lower respiratory tract samples for galactomannan assay, direct microscopy, culture, and bacterial, fungal and viral PCR. In case of positive Aspergillus testing, chest CT is the imaging modality of choice. If influenza pneumonia is diagnosed, neuraminidase inhibitors are the preferred approved drugs. When invasive aspergillosis is confirmed, first-line therapy consists of isavuconazole or voriconazole. Isavuconazole is an alternative in case of intolerance to voriconazole, drug-drug interactions, renal impairment, or if a spectrum of activity including the majority of Mucorales is desired. Primary anti-mould prophylaxis with posaconazole is recommended in haematology patients at high-risk. It may be considered in newly diagnosed influenza and ARDS, but ideally in clinical trials.
The rising reports of influenza-associated pulmonary aspergillosis in patients with ARDS, who are otherwise not considered at risk for fungal pneumonia demands heightened clinical awareness. Tracheobronchitis and Aspergillus in respiratory tract samples should prompt suspicion of invasive fungal infection and further work-up. The management algorithm should comprise bronchoalveolar lavage, CT imaging, sophisticated ventilator-management, rescue extracorporeal membrane oxygenation, and antifungal and antiviral therapy. To decrease the burden of influenza-related illness, vaccination is of utmost importance, specifically in patients with co-morbidities.
严重肺部感染是重症监护病房（ICU）收治的最常见原因之一。在过去十年中，越来越多的严重流感肺炎导致急性呼吸窘迫综合征（ARDS）并合并曲霉菌感染的报告发表。
提供一个关于 ARDS 患者流感相关肺曲霉菌病管理的综合综述。
对严重流感相关性肺曲霉菌病的文献回顾。在 PubMed 数据库中检索了自数据库成立至 2019 年 1 月的出版物。
对于有下呼吸道症状的患者，呼吸功能不全的发展应引发快速和彻底的临床评估，特别是在疑似 ARDS 的情况下，包括心电图和超声心动图以排除心功能障碍、心律失常和缺血。支气管肺泡灌洗应获取下呼吸道样本进行半乳甘露聚糖检测、直接显微镜检查、培养以及细菌、真菌和病毒 PCR。如果曲霉检测呈阳性，胸部 CT 是首选的影像学检查方法。如果诊断为流感肺炎，神经氨酸酶抑制剂是首选的批准药物。如果确诊侵袭性曲霉病，一线治疗包括伊曲康唑或伏立康唑。如果不能耐受伏立康唑、药物相互作用、肾功能损害，或需要包括大多数毛霉菌在内的广谱活性，伊曲康唑是替代药物。对于高危血液病患者，建议进行原发性抗真菌预防治疗。对于新诊断的流感和 ARDS，也可以考虑，但最好在临床试验中进行。
在其他情况下不被认为有真菌感染风险的 ARDS 患者中，流感相关性肺曲霉菌病的报道不断增加，这需要提高临床认识。气管支气管炎和呼吸道样本中的曲霉应提示侵袭性真菌感染的怀疑，并进一步检查。管理算法应包括支气管肺泡灌洗、CT 成像、复杂的通气管理、抢救性体外膜氧合和抗真菌和抗病毒治疗。为了降低流感相关疾病的负担，疫苗接种至关重要，特别是对合并症患者。
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