Milsap Dominique, Okuno Madison, Kigozi Enos, Mugabi Timothy, Faizo Ssekindi, Bajer Aleksandra, Gakuru Jane, Bahr Nathan C
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Microorganisms. 2025 Apr 8;13(4):847. doi: 10.3390/microorganisms13040847.
Cryptococcal meningitis remains a leading cause of morbidity and mortality among individuals with HIV/AIDS, particularly in resource-limited settings. Treatment begins with induction therapy followed by consolidation and maintenance. Evidence related to induction therapy has evolved significantly over the past decade. Current treatment relies primarily on three antifungal agents: amphotericin B, flucytosine, and fluconazole, each with distinct mechanisms of action and limitations. The World Health Organization's 2022 guidelines for induction therapy recommend a single high dose of liposomal amphotericin B combined with 14 days of flucytosine and fluconazole. The 2010 IDSA guidelines for induction therapy recommend amphotericin B deoxycholate and flucytosine for two weeks. The U.S. CDC/NIH/IDSA/HIVMA joint guidelines and the ECCM/ISHAM/ASM joint guidelines list both options, but the recommendation varies by setting resources (e.g., resource-limited vs. other). The newer treatment approaches (single high-dose liposomal amphotericin B) that are supported by trials such as AMBITION-cryptococcal meningitis have limited adoption in high-resource settings, with recent studies showing that only 14% of North American infectious disease providers have utilized the regimen. Adjunctive medications, such as dexamethasone, tamoxifen, and sertraline, have proven ineffective or harmful in clinical trials. This review underscores the ongoing challenges in cryptococcal meningitis treatment and the need for continued research to improve patient outcomes, tracing the evolution from past monotherapy approaches to current combination strategies while exploring future directions.
隐球菌性脑膜炎仍然是艾滋病毒/艾滋病患者发病和死亡的主要原因，在资源有限的环境中尤为如此。治疗始于诱导治疗，随后是巩固治疗和维持治疗。在过去十年中，与诱导治疗相关的证据有了显著发展。目前的治疗主要依赖三种抗真菌药物：两性霉素B、氟胞嘧啶和氟康唑，每种药物都有独特的作用机制和局限性。世界卫生组织2022年诱导治疗指南推荐单次高剂量脂质体两性霉素B联合14天的氟胞嘧啶和氟康唑。2010年美国感染病学会（IDSA）诱导治疗指南推荐使用脱氧胆酸两性霉素B和氟胞嘧啶治疗两周。美国疾病控制与预防中心（CDC）/美国国立卫生研究院（NIH）/IDSA/美国艾滋病毒医学协会（HIVMA）联合指南以及欧洲临床微生物学和传染病学会（ECCM）/国际人类与动物真菌学会（ISHAM）/美国微生物学会（ASM）联合指南都列出了这两种选择，但建议因资源情况（如资源有限与其他情况）而异。像AMBITION-隐球菌性脑膜炎等试验支持的较新治疗方法（单次高剂量脂质体两性霉素B）在资源丰富的环境中采用率有限，最近的研究表明，北美只有14%的传染病医疗服务提供者使用了该方案。辅助药物，如地塞米松、他莫昔芬和舍曲林，在临床试验中已被证明无效或有害。本综述强调了隐球菌性脑膜炎治疗中持续存在的挑战以及持续开展研究以改善患者预后的必要性，追溯了从过去的单一疗法到当前联合策略的演变过程，同时探索未来的发展方向。
