High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV: a randomised study

Abstract number: 1732_103

Bicanic T., Meintjes G., Wood R., Rebe K., Brouwer A., Bekker L-G., Harrison T.

Objectives: To determine the early fungicidal activity (EFA) and toxicity of high dose amphotericin B (AmB, 1 mg/kg/d) plus flucytosine (5FC) compared with standard dose amphotericin B (0.7 mg/kg/d) plus flucytosine for the treatment of HIV-associated cryptococcal meningitis.

Methods: 64 HIV positive antiretroviral therapy naive patients, presenting with a first episode of cryptococcal meningitis in Cape Town, South Africa from May 2005 to June 2006, were randomised to receive either amphotericin B 0.7 mg/kg/d plus flucytosine 25 mg/kg qds (Group 1) or amphotericin B 1 mg/kg/d plus flucytosine 25 mg/kg qds (Group 2) for 2 weeks, followed by oral fluconazole. EFA was evaluated by the rate of reduction in CSF cryptococcal colony-forming units (CFU) determined from serial quantitative CSF cultures on days 1, 3, 7, and 14 of treatment. Follow-up was 10 weeks.

Results: Median CD4 count was 38×106/L. 13% of patients had abnormal mental status. Mean (SD) early fungicidal activity was -0.56 (0.24) log CFU/mL CSF/d for AmB at 1 mg/kg/d plus 5FC and -0.45 (0.16) CFU/mL CSF/d for AmB at 0.7 mg/kg/d plus 5FC. As in prior studies, baseline count was associated with rate of clearance. In a linear regression model including treatment group and baseline count, EFA was significantly greater for AmB at 1 mg/kg/d plus 5FC compared with AmB at 0.7 mg/kg/d plus 5FC (difference 0.12 log CFU/d [95% CI: 0.02–0.23], p = 0.02). There was a trend towards a greater rise in creatinine in Group 2 versus Group 1: final creatinine increased by 88% vs 52% from baseline (p = 0.08), which was reversible on stopping study drug treatment. Mortality was 23% (15/64) at 10 weeks with no difference between the two groups.

Conclusions: Amphotericin B at 1mg/kg/d with flucytosine is more rapidly fungicidal in the treatment of HIV-associated cryptococcal meningitis compared to standard dose amphotericin B. Increasing the dose of amphotericin B did not result in a clinically significant increase in nephrotoxicity.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Location: ICC, Munich, Germany
Presentation type:
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