Single-Dose Liposomal Amphotericin Plus Fluconazole and Flucytosine for Cryptococcal Meningitis at a US Public Hospital.

Importance: Cryptococcal meningitis (CM) is a significant cause of mortality and morbidity in people with HIV. Standard induction therapy for CM-amphotericin with flucytosine-is associated with significant toxic effects. Objective: To assess mortality and CM recurrence outcomes of the AMBITION protocol (single-dose liposomal amphotericin with 2 weeks of fluconazole and flucytosine) for treatment of CM in a high-resource setting. Design, Setting, and Participants: This pre-post cohort study conducted at Los Angeles General Medical Center, a large safety net hospital (80% Medicaid-covered, 5% uninsured), included people with HIV treated for CM with the AMBITION protocol from August 1, 2022, to July 31, 2024, and a control population receiving a guideline-compliant, daily amphotericin-based regimen from August 1, 2020, to July 31, 2022. Exclusion criteria included age less than 18 years, alternative diagnosis, transfer during induction, and death within 48 hours of admission. Exposures: AMBITION protocol with single infusion of liposomal amphotericin (10 mg/kg) and 14 days of high-dose fluconazole (1200 mg/d) and flucytosine (100 mg/kg/d). The control group was treated with lipid-based amphotericin (3-5 mg/kg/d) and flucytosine (100 mg/kg/d) for 14 days. Main Outcome and Measures: The primary end point was treatment success, defined as a composite of survival without recurrence or severe adverse events at 90 days. Results: A total of 60 eligible patient episodes were identified during the study period (54 [90.0%] among males; median patient age, 40 [IQR, 34-51] years). In all, 34 patients (56.7%) were treated with the AMBITION protocol, compared with 26 (43.3%) receiving the control regimen. Loss to follow-up by 90 days occurred in 6 patients in the control group (23.1%) and 9 intervention patients (26.5%) (P = .76). Of patients with available data, the composite outcome occurred in 19 of 25 patients receiving the AMBITION protocol (76.0%) compared with 7 of 20 patients in the control group (35.0%) (P = .006). The difference in composite outcome rates was driven by fewer severe adverse events in the AMBITION arm (7 [20.6%] vs 16 [61.5%]; P = .001). Additionally, patients receiving the AMBITION protocol had fewer patient-directed discharges (4 [11.8%] vs 9 [34.6%]; P = .03). Conclusions and Relevance: In this pre-post study of HIV-associated CM, fewer severe adverse effects were seen in patients receiving the AMBITION protocol compared with a daily amphotericin-based regimen, with no difference in mortality or recurrence. There were also fewer patient-directed discharges, suggesting more patient-centered care. These findings support broader adoption of the AMBITION protocol in high-resource settings.