Interaction between posaconazole and amphotericin B in concomitant treatment against Candida albicans in vivo

Abstract

The interaction of posaconazole and amphotericin B was evaluated in concomitant treatment of Candida albicans systemic infections in immunocompetent mice by using four strains of C. albicans with different susceptibilities to fluconazole. Posaconazole and amphotericin B were each tested at four dose levels alone and in all possible combinations against each C. albicans strain. Survival curves of mice treated with combinations of posaconazole and amphotericin B were statistically compared with those of mice treated with the component monotherapies. Of the 64 total combinations evaluated against the C. albicans strains (16 combinations per strain), 20.3% were more effective in prolonging mouse survival than both of the monotherapies, 45.3% were more effective than one of the monotherapies, and 32.8% were similar to both monotherapies. No evidence of antagonism was observed between posaconazole and amphotericin B in this mouse model, consistent with in vitro results against the same strains.

FIG. 1.

Concomitant combination treatment with POS and AMB of systemic infection in mice with FLC-S C. albicans C43 (A) or FLC-R C. albicans C284 (B). The combination of POS and AMB, POS alone, or AMB alone was administered once daily for 4 days starting 4 h postinfection on day 0. Dose levels (in milligrams/kilogram of body weight) are indicated in parentheses. Controls were administered sterile water for injection. The survival data were averaged from two experiments (10 mice per group in each experiment). The P values were determined by comparing the survival curve for the combination to each of those for the drugs alone.