Gakuru Jane, Kagimu Enock, Dai Biyue, Okurut Samuel, Nsangi Laura, Bahr Nathan C, Okirwoth Michael, Namuju Olivie C, Jarvis Joseph N, Lawrence David S, Ahimbisibwe Cynthia, Ellis Jayne, Tadeo Kizza Kandole, Boulware David R, Meya David B, Tugume Lillian
Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Division of Biostatistics and Health Data Science, University of Minnesota, Minneapolis, Minnesota, USA.
Clin Infect Dis. 2025 Feb 24;80(2):417-424. doi: 10.1093/cid/ciae413.
In 2022, the World Health Organization (WHO) recommended a single 10 mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of human immunodeficiency virus (HIV)-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda.
We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites.
During 2022-2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018 to 2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95% confidence interval [CI]: 61.6%-76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95% CI: 65.2%-78.8%; absolute risk difference = -3.1%; 95% CI: -13.1% to 6.9%; P = .61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; P = .80) between groups. Among observational cohort participants discharged alive initially and for whom follow-up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144).
The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.
2022年，基于多中心AMBITION-cm试验的结果，世界卫生组织（WHO）推荐采用单剂量10 mg/kg的脂质体两性霉素B联合14天的氟胞嘧啶和氟康唑（AMBITION-cm方案）用于人类免疫缺陷病毒（HIV）相关隐球菌性脑膜炎的诱导治疗。我们评估了在乌干达实际应用这一新方案后的疗效。
我们将患有隐球菌性脑膜炎的乌干达成年人纳入一个观察性队列，在2022年至2023年的常规护理中接受AMBITION-cm方案并进行治疗性腰椎穿刺。我们将10周生存率和脑脊液早期杀菌活性与在同一地点进行的AMBITION-cm临床试验中观察到的结果进行了比较。
在2022年至2023年期间，179名成年人通过常规护理接受了AMBITION-cm方案治疗，并与2018年至2021年在乌干达随机分配到AMBITION-cm试验干预组的171名成年人进行了比较。观察性队列（68.6%；95%置信区间[CI]：61.6%-76.3%）和干预组的AMBITION-cm试验参与者之间的10周生存率没有显著差异（71.7%；95%CI：65.2%-78.8%；绝对风险差异 = -3.1%；95%CI：-13.1%至6.9%；P = 0.61）。两组之间的早期杀菌活性没有差异（分别为0.42对0.39 log10CFU/mL/天；P = 0.80）。在最初存活出院且有随访数据的观察性队列参与者中，因颅内压持续升高而再次住院的发生率为2.8%（4/144）。
用于隐球菌性脑膜炎的AMBITION-cm方案在常规护理中实施时，其疗效与AMBITION-cm临床试验中观察到的相似。住院期间的颅内压管理和出院后的认知是优化疗效的关键组成部分。
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