Treatment of Cryptococcal Meningitis Associated with the Acquired Immunodeficiency Syndrome
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Discussion
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Implication
Randomized double-blind trial shows higher-dose amphotericin B with flucytosine improves fungal clearance in AIDS-associated cryptococcal meningitis, indicating more effective induction therapy.
Key Points
- To compare the efficacy and safety of higher-dose amphotericin B with or without flucytosine, followed by consolidation therapy with fluconazole or itraconazole, in patients with AIDS-associated cryptococcal meningitis.
- Conducted a double-blind multicenter randomized trial in patients presenting with a first episode of AIDS-associated cryptococcal meningitis.
- Step one (initial two weeks) evaluated amphotericin B (0.7 mg/kg/day) with or without flucytosine (100 mg/kg/day).
- Step two (subsequent eight weeks) randomized patients to consolidation therapy with either fluconazole (400 mg/day) or itraconazole (400 mg/day).
- At two weeks, cerebrospinal fluid cultures were negative in 60% of 202 patients receiving amphotericin B plus flucytosine compared with 51% of 179 receiving amphotericin B alone (P=0.06).
- At 10 weeks, negative cultures occurred in 72% of 151 fluconazole recipients versus 60% of 155 itraconazole recipients (95% CI for the difference in percentages, -100 to 21), while clinical response rates were 68% and 70%, respectively.
- Overall mortality was 5.5% during the first two weeks and 3.9% during the next eight weeks, with multivariate analysis identifying initial flucytosine and subsequent fluconazole as independent predictors of cerebrospinal fluid sterilization.
Cite This Study
Horst et al. (1997) studied this question.