{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:52:06Z","timestamp":1789692726507,"version":"4.0.1"},"reference-count":16,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Cryptococcal meningitis (CM) is a significant cause of mortality and morbidity in people with HIV. Standard induction therapy for CM\u2014amphotericin with flucytosine\u2014is associated with significant toxic effects.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Main Outcome and Measures<\/jats:title>\n The primary end point was treatment success, defined as a composite of survival without recurrence or severe adverse events at 90 days.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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%) (\n P<\/jats:italic>\n \u2009=\u2009.76). 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%) (\n P<\/jats:italic>\n \u2009=\u2009.006). The difference in composite outcome rates was driven by fewer severe adverse events in the AMBITION arm (7 [20.6%] vs 16 [61.5%];\n P<\/jats:italic>\n \u2009=\u2009.001). Additionally, patients receiving the AMBITION protocol had fewer patient-directed discharges (4 [11.8%] vs 9 [34.6%];\n P<\/jats:italic>\n \u2009=\u2009.03).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.53552","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T16:00:16Z","timestamp":1769011216000},"page":"e2553552","source":"Crossref","is-referenced-by-count":5,"title":["Single-Dose Liposomal Amphotericin Plus Fluconazole and Flucytosine for Cryptococcal Meningitis at a US Public Hospital"],"prefix":"10.1001","volume":"9","author":[{"given":"Devin","family":"Clark","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles General Medical Center, Los Angeles, California"},{"name":"Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Barranco-Trabi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Los Angeles 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