Therapeutic efficacy of voriconazole against a fluconazole-resistant Candida albicans isolate in a vaginal model

Abstract

Background: The purpose of this study was to assess the therapeutic efficacy of oral versus intravaginal voriconazole and compare it with fluconazole for the treatment of experimental vaginitis caused by a fluconazole-resistant Candida albicans isolate. Methods: Mice were treated with voriconazole at 5, 10 and 20 mg/kg once a day and 20 mg/kg twice a day or with fluconazole at 20 mg/kg once or twice a day orally. Intravaginal treatments were evaluated with voriconazole and fluconazole at 0.5, 1 and 5 mg/kg once a day. All treatment regimens were given on days 1-5 post-challenge. One day 6, the vaginas were swabbed to assess treatment effects. Results Mice treated orally with voriconazole at ≥10 mg/kg and fluconazole at ≥20 mg/kg showed significantly reduced fungal counts over controls (P = 0.0002 - 0.007). Significant differences were found between the groups that received voriconazole at 20 mg/kg once or twice daily and those that received fluconazole at 20 mg/kg once or twice daily, orally (P = 0.010 and 0.001, respectively). Mice treated with voriconazole or fluconazole administered intravaginally at ≥0.5 mg/kg exhibited a reduced fungal burden when compared with the control group (P = 0.0002-0.007). There was no statistically significant difference in fungal burden between topical treatment with doses of 0.5, 1 and 5 mg/kg once daily of voriconazole or fluconazole. Sterilization of vaginas was not observed with voriconazole and fluconazole without taking into consideration the therapeutic modality. Conclusions: Voriconazole could emerge as a new alternative for treatment of vaginal candidosis. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.