Neuroinfections caused by fungi.
Neuroinfections caused by fungi.
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DOI：
10.1007/s15010-018-1152-2
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发表时间：
2018-08
期刊：
影响因子：
7.5
通讯作者：
Dzikowiec M
中科院分区：
文献类型：
--
作者：
Góralska K;Blaszkowska J;Dzikowiec M
中枢神经系统真菌感染（FIS-CNS）在过去20年中变得更加常见。CNS的侵袭在很大程度上取决于宿主的免疫状态和真菌菌株的毒力。真菌感染在免疫功能低下的宿主中引起显著的发病率，并且CNS的参与可能导致致命的后果。在PubMed、Google Scholar和科克伦数据库中选择135篇关于真菌神经感染的文章进行综述，使用以下检索词：“真菌和CNS真菌病”、CNS真菌感染”、“真菌性脑感染”、“真菌性脑炎”、“真菌性脑膜炎”、“真菌感染的诊断”和“CNS真菌感染的治疗”。所有报告都以英文出版，其中大部分是在2000-2018年期间出版的。本文综述了目前的流行病学知识，临床表现，诊断和治疗选定的FIS-CNS。FIS-CNS可具有各种临床表现，主要是脑膜炎、脑炎、脑积水、脑水肿和中风综合征。神经感染的病原学因素是酵母菌（新型隐球菌，念珠菌属，丝孢酵母属（Trichosporon spp.），念珠状霉菌（曲霉属，镰刀菌属（Fusarium spp.），毛霉纲（毛霉属，根霉属（Rhizopus spp.），二型真菌（皮肤芽生菌，球孢子菌属，荚膜组织胞浆菌）和暗色真菌（班氏刚毛瓶霉（Cladophialophora bantiana）、皮外瓶霉（Exophialadermativae））。它们的常见传播途径是吸入或创伤或手术接种，随后通过血源性或邻近传播。由于FIS-CNS的临床表现往往无特异性，诊断非常困难。快速识别神经感染的病因和应用适当的治疗是预防致命后果的关键。有效药物的选择取决于其CNS渗透的程度和活性谱。阿替霉素B（AmB）的药物制剂（其中包括脱氧胆酸盐-AmBd和脂质体L-AmB）在脑脊液（CSF）中的分布相对有限;然而，其在CNS中的可检测治疗浓度使其成为治疗隐球菌脑膜脑炎（AmBd+氟胞嘧啶）和CNS念珠菌病（L-AmB）和毛霉菌病（L-AmB）的推荐药物。伏立康唑是一种中等亲脂性分子，具有良好的CNS渗透性，推荐用于CNS曲霉病的一线治疗。其他三唑类药物，如泊沙康唑和伊曲康唑，在CSF中的浓度可忽略不计，被认为不是治疗CNS真菌性神经感染的有效药物。与此相反，临床数据表明，一种新的三唑，艾沙康唑，取得了相当大的疗效，用于治疗一些真菌性神经感染。CSF中浓度相对较低或检测不到的棘白菌素在治疗FIS-CNS中不起有意义的作用。虽然引起CNS真菌病的真菌种类的数量正在增加，但只有一些具有明确的治疗标准（例如，隐球菌性脑膜炎和CNS曲霉病）。真菌感染的早期诊断，伴随着病原学因素的鉴定，需要允许选择有效的治疗与FIS-CNS患者，并限制其高死亡率。
Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences. One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: “fungi and CNS mycoses”, CNS fungal infections”, “fungal brain infections”, " fungal cerebritis”, fungal meningitis”, “diagnostics of fungal infections”, and “treatment of CNS fungal infections”. All were published in English with the majority in the period 2000–2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS. The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS. Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.
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DOI：
10.11604/pamj.2016.24.232.9688
发表时间：
2016
期刊：
The Pan African medical journal
影响因子：
--
作者：
Bozorgi V;Talebitaher M;Shalbaf N;Radmanesh N;Nasri F;Ansari-Ramandi MM
通讯作者：
Ansari-Ramandi MM
影响因子：
11.8
作者：
Chapman, Stanley W.;Dismukes, William E.;Kauffman, Carol A.
通讯作者：
Kauffman, Carol A.
影响因子：
9.4
作者：
Chong, G. M.;Maertens, J. A.;Rijnders, B. J. A.
通讯作者：
Rijnders, B. J. A.
影响因子：
2
作者：
Bourne, Emma-Lee;Dimou, James
通讯作者：
Dimou, James
影响因子：
2.2
作者：
Bagla, Prabhava;Loeffelholz, Michael;Blanton, Lucas S.
通讯作者：
Blanton, Lucas S.