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毛霉病:一种持续性毁灭性感染的新进展

Mucormycosis: New Developments into a Persistently Devastating Infection.

作者信息

Danion François, Aguilar Claire, Catherinot Emilie, Alanio Alexandre, DeWolf Susan, Lortholary Olivier, Lanternier Fanny

机构信息

Service de Maladies Infectieuses et tropicales, APHP-Hôpital Necker-Enfants Malades, Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, Paris, France.

Institut Pasteur, Unité de Mycologie Moléculaire, CNRS URA3012, Paris, France.

出版信息

Semin Respir Crit Care Med. 2015 Oct;36(5):692-705. doi: 10.1055/s-0035-1562896. Epub 2015 Sep 23.

Abstract

Mucormycosis is a rare, though increasingly prevalent, life-threatening fungal disease caused by Mucorales. The incidence has increased over the last decade and its mortality remains high at around 50%. Mucormycosis occurs mostly in patients with diabetes mellitus and/or in the context of immunosuppression resulting from chemotherapy for hematological malignancy, hematopoietic stem cell transplantation, or solid-organ transplantation. In this situation, lung and rhino-orbito-cerebral infections are the most frequent localizations of the disease. Prompt initiation of an effective treatment is essential to decrease mortality. However, mucormycosis and aspergillosis share close clinical and radiological features. Invasive procedures such as bronchial endoscopy and/or lung biopsy are necessary to confirm diagnosis, as no indirect tests are yet validated. Therefore, the challenge is to minimize the delay in diagnosis. When present, the reversed halo sign on CT scan is suggestive of mucormycosis. Quantitative polymerase chain reaction is a new promising approach to detect Mucorales DNA in serum and new molecular tools are available to detect Mucorales in tissues as well as to specify species. Recommendations from ECIL and ECMM/ESCMID have recently been published on management of mucormycosis. The recommended treatment is an amphotericin B lipid formulation in combination with surgery and modification of risk factors. High-dose (10 mg/kg) of liposomal amphotericin B is recommended in case of neurological involvement and posaconazole for maintenance therapy. Place of isavuconazole as well as posaconazole new formulations (tablets and intravenous) in first line treatment have to be defined. Improved radiologic descriptions of mucormycosis and new molecular tools may be key elements to help with rapid diagnosis in the future. Clinical trials are warranted to improve therapeutic success and hopefully survival.

摘要

毛霉病是一种由毛霉目真菌引起的罕见但日益普遍的危及生命的真菌病。在过去十年中,其发病率有所上升,死亡率仍高达50%左右。毛霉病大多发生于糖尿病患者和/或因血液系统恶性肿瘤化疗、造血干细胞移植或实体器官移植导致免疫抑制的情况下。在此情形下,肺部和鼻眶脑感染是该病最常见的发病部位。迅速开始有效的治疗对于降低死亡率至关重要。然而,毛霉病和曲霉病在临床和影像学特征上有相似之处。由于尚无间接检测方法得到验证,因此需要进行支气管内镜检查和/或肺活检等侵入性操作来确诊。所以,挑战在于尽量减少诊断延迟。CT扫描出现反晕征提示毛霉病。定量聚合酶链反应是检测血清中毛霉目DNA的一种有前景的新方法,并且有新的分子工具可用于检测组织中的毛霉目真菌以及鉴定菌种。欧洲感染病学会(ECIL)和欧洲医学真菌学联合会/欧洲临床微生物学与传染病学会(ECMM/ESCMID)最近发布了关于毛霉病管理的建议。推荐的治疗方法是使用两性霉素B脂质制剂联合手术及改善危险因素。对于有神经系统受累的病例,推荐使用高剂量(10mg/kg)的脂质体两性霉素B,泊沙康唑用于维持治疗。必须明确艾沙康唑以及泊沙康唑新剂型(片剂和静脉制剂)在一线治疗中的地位。对毛霉病改进的影像学描述和新的分子工具可能是未来有助于快速诊断的关键因素。有必要开展临床试验以提高治疗成功率并有望提高生存率。

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