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Guidelines recommend combination therapy with amphotericin B and flucytosine, but standard flucytosine dosing of 100\u2005mg\/kg\/day is associated with hematologic toxicity. The FLOOR trial investigated whether lower flucytosine dosing maintained therapeutic efficacy and reduced toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This phase 2, single-arm, open-label trial enrolled 48 adults with HIV and confirmed cryptococcal meningitis at 2 hospitals in Uganda. Participants received 10 days of flucytosine at 60\u2005mg\/kg\/day in 3 divided doses, combined with liposomal amphotericin B (10\u2005mg\/kg, single dose) and fluconazole 1200 mg\/day for 14 days, followed by standard consolidation therapy. The primary endpoint was the early fungicidal activity (EFA), which measures the rate of Cryptococcus clearance in the cerebrospinal fluid (CSF) in the first 14 days of therapy. Secondary endpoints included CSF sterility at 2 weeks, 18-week survival, and adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The EFA of reduced dose flucytosine was 0.28\u2005log10 colony forming units (CFU)\/mL\/day (95% CI, .20 to .35), which was lower than historical controls in Uganda receiving flucytosine at 100\u2005mg\/kg\/day of 0.41\u2005log10 CFU\/mL\/day (P = .019). At 18 weeks, the estimated survival probability was 77% (95% CI, 66% to 90%). The incidence of rehospitalization (25%) and culture-positive relapse (6.3%) were higher than expected. Grades 3 and 4 hematologic toxicity was similar (10% leukopenia; 21% anemia) to historical incidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Reduced flucytosine dose of 60\u2005mg\/kg\/day for 10 days demonstrated inferior efficacy in CSF fungal clearance. These findings support further investigation of dose optimization strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov: NCT06414512.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf432","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T11:37:14Z","timestamp":1754480234000},"page":"67-74","source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the Use of Lower Dose Flucytosine for the Treatment of Cryptococcal Meningitis: A Clinical Trial"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2276-360X","authenticated-orcid":false,"given":"Morris K","family":"Rutakingirwa","sequence":"first","affiliation":[{"name":"Department of Research, Infectious Diseases Institute, College of Health Sciences, Makerere University , Kampala 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