Srichatrapimuk Sirawat, Sungkanuparph Somnuek
Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samutprakan, Thailand.
Division of Infectious Diseases, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
AIDS Res Ther. 2016 Nov 29;13(1):42. doi: 10.1186/s12981-016-0126-7.
Cryptococcosis has been one of the most common opportunistic infections and causes of mortality among HIV-infected patients, especially in resource-limited countries. Cryptococcal meningitis is the most common form of cryptococcosis. Laboratory diagnosis of cryptococcosis includes direct microscopic examination, isolation of Cryptococcus from a clinical specimen, and detection of cryptococcal antigen. Without appropriate treatment, cryptococcosis is fatal. Early diagnosis and treatment is the key to treatment success. Treatment of cryptococcosis consists of three main aspects: antifungal therapy, intracranial pressure management for cryptococcal meningitis, and restoration of immune function with antiretroviral therapy (ART). Optimal integration of these three aspects is crucial to achieving successful treatment and reducing the mortality. Antifungal therapy consists of three phases: induction, consolidation, and maintenance. A combination of two drugs, i.e. amphotericin B plus flucytosine or fluconazole, is preferred in the induction phase. Fluconazole monotherapy is recommended during consolidation and maintenance phases. In cryptococcal meningitis, intracranial pressure rises along with CSF fungal burden and is associated with morbidity and mortality. Aggressive control of intracranial pressure should be done. Management options include therapeutic lumbar puncture, lumbar drain insertion, ventriculostomy, or ventriculoperitoneal shunt. Medical treatment such as corticosteroids, mannitol, and acetazolamide are ineffective and should not be used. ART has proven to have a great impact on survival rates among HIV-infected patients with cryptococcosis. The time to start ART in HIV-infected patients with cryptococcosis has to be deferred until 5 weeks after the start of antifungal therapy. In general, any effective ART regimen is acceptable. Potential drug interactions between antiretroviral agents and amphotericin B, flucytosine, and fluconazole are minimal. Of most potential clinical relevance is the concomitant use of fluconazole and nevirapine. Concomitant use of these two drugs should be cautious, and patients should be monitored closely for nevirapine-associated adverse events, including hepatotoxicity. Overlapping toxicities of antifungal and antiretroviral drugs and immune reconstitution inflammatory syndrome are not uncommon. Early recognition and appropriate management of these consequences can reinforce the successful integrated therapy in HIV-infected patients with cryptococcosis.
隐球菌病一直是HIV感染患者中最常见的机会性感染之一和死亡原因，尤其是在资源有限的国家。隐球菌性脑膜炎是隐球菌病最常见的形式。隐球菌病的实验室诊断包括直接显微镜检查、从临床标本中分离出隐球菌以及检测隐球菌抗原。若不进行适当治疗，隐球菌病是致命的。早期诊断和治疗是治疗成功的关键。隐球菌病的治疗包括三个主要方面：抗真菌治疗、隐球菌性脑膜炎的颅内压管理以及通过抗逆转录病毒疗法（ART）恢复免疫功能。这三个方面的最佳整合对于实现成功治疗和降低死亡率至关重要。抗真菌治疗包括三个阶段：诱导、巩固和维持。诱导阶段首选两种药物联合使用，即两性霉素B加氟胞嘧啶或氟康唑。巩固和维持阶段推荐氟康唑单药治疗。在隐球菌性脑膜炎中，颅内压随脑脊液真菌负荷升高而升高，并与发病率和死亡率相关。应积极控制颅内压。管理选项包括治疗性腰椎穿刺、腰大池引流管置入、脑室造瘘术或脑室腹腔分流术。皮质类固醇、甘露醇和乙酰唑胺等药物治疗无效，不应使用。ART已被证明对感染HIV的隐球菌病患者的生存率有很大影响。感染HIV的隐球菌病患者开始ART的时间必须推迟到抗真菌治疗开始后5周。一般来说，任何有效的ART方案都是可以接受的。抗逆转录病毒药物与两性霉素B、氟胞嘧啶和氟康唑之间的潜在药物相互作用极小。最具潜在临床相关性的是氟康唑和奈韦拉平的同时使用。这两种药物同时使用时应谨慎，并且应密切监测患者是否出现与奈韦拉平相关的不良事件，包括肝毒性。抗真菌药和抗逆转录病毒药的重叠毒性以及免疫重建炎症综合征并不少见。对这些后果的早期识别和适当管理可以加强对感染HIV的隐球菌病患者的成功综合治疗。
