Treatment of cryptococcal meningitis with low-dose amphotericin B and flucytosine

Amphotericin B (0.7 mg/kg) with flucytosine is the standard treatment for cryptococcal meningitis. However, the long treatment course can induce adverse reactions in patients; therefore, reducing the dose may decrease such reactions. We performed a retrospective analysis of treatment effects and adverse reactions when amphotericin B (0.4 mg/kg or 0.7 mg/kg per day) and flucytosine were used together to treat HIV-negative patients with cryptococcal meningitis.

Retrospective analysis was conducted on inpatients at the First Affiliated Hospital, College of Medicine, Zhejiang University (January 2005 to December 2009). Low- or high-dose amphotericin B (0.4 or 0.7 mg/kg per day, respectively) plus flucytosine was used. The negative conversion rate of Cryptococcus in the cerebrospinal fluid (CSF), patient mortality, and the incidence of side effects for the two groups (low- vs. high-dose) were compared immediately after treatment and 2 and 10 weeks later. Data were analyzed by the Student's t test, chi-square tests using SPSS 12.0 statistical software.

Two weeks post-treatment, Cryptococcus negative CSF rates were 78% (18/23) in the low-dose group and 87% (13/15) in the high-dose group (P = 0.28). Ten weeks post-treatment, both groups were negative. The mortality rate was 8% (2/25) in the low-dose group and 17% (3/18) in the high-dose group (P = 0.25). There was a statistically significant difference in the incidence of adverse events between the groups, 48% (12/25) and 78% (14/18) in the low- and high-dose groups, respectively (P = 0.04). Adverse events that required a change in treatment program in the low-dose group were 12% (3/25) compared to 39% (7/18) in the high-dose group (P = 0.04).

Low-dose treatment regimens were better tolerated than high-dose ones.