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

Cacciapuoti A, Gurnani M, Halpern J, Norris C, Patel R, Loebenberg D

Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033, USA. anthony.cacciapuoti@spcorp.com

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.

Published 27 January 2005 in Antimicrob Agents Chemother, 49(2): 638-42.
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