Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Clin Microbiol Rev. 2023 Dec 20;36(4):e0015622. doi: 10.1128/cmr.00156-22. Epub 2023 Nov 28.
Cryptococcal meningitis is a leading cause of morbidity and mortality globally, especially in people with advanced HIV disease. Cryptococcal meningitis is responsible for nearly 20% of all deaths related to advanced HIV disease, with the burden of disease predominantly experienced by people in resource-limited countries. Major advancements in diagnostics have introduced low-cost, easy-to-use antigen tests with remarkably high sensitivity and specificity. These tests have led to improved diagnostic accuracy and are essential for screening campaigns to reduce the burden of cryptococcosis. In the last 5 years, several high-quality, multisite clinical trials have led to innovations in therapeutics that have allowed for simplified regimens, which are better tolerated and result in less intensive monitoring and management of medication adverse effects. One trial found that a shorter, 7-day course of deoxycholate amphotericin B is as effective as the longer 14-day course and that flucytosine is an essential partner drug for reducing mortality in the acute phase of disease. Single-dose liposomal amphotericin B has also been found to be as effective as a 7-day course of deoxycholate amphotericin B. These findings have allowed for simpler and safer treatment regimens that also reduce the burden on the healthcare system. This review provides a detailed discussion of the latest evidence guiding the clinical management and special circumstances that make cryptococcal meningitis uniquely difficult to treat.
隐球菌性脑膜炎是全球发病率和死亡率的主要原因,特别是在晚期 HIV 疾病患者中。隐球菌性脑膜炎导致近 20%的所有与晚期 HIV 疾病相关的死亡,疾病负担主要由资源有限的国家的人们承担。诊断方面的重大进展引入了低成本、易于使用的抗原检测,具有极高的灵敏度和特异性。这些测试提高了诊断准确性,对于减少隐球菌病负担的筛查活动至关重要。在过去 5 年中,几项高质量、多地点的临床试验推动了治疗方法的创新,简化了治疗方案,提高了患者的耐受性,并减少了药物不良反应监测和管理的强度。一项试验发现,脱氧胆酸盐两性霉素 B 的 7 天疗程与 14 天疗程一样有效,氟胞嘧啶是降低疾病急性期死亡率的必需联合药物。单剂量脂质体两性霉素 B 也被发现与 7 天疗程的脱氧胆酸盐两性霉素 B 一样有效。这些发现使得治疗方案更加简单和安全,同时也减轻了医疗保健系统的负担。本综述详细讨论了指导临床管理的最新证据以及使隐球菌性脑膜炎治疗变得独特困难的特殊情况。