Interaction between Posaconazole and Amphotericin B in Concomitant Treatment against Candida albicans In Vivo

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. The clinical use of azoles in combination with amphotericin B (AMB) is still controversial because of the potential for antagonism between the two drugs (9, 12, 18, 22). This poten-tial comes from their mechanisms of action; azoles block er-gosterol biosynthesis, while AMB causes membrane damage b