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

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 >or=10 mg/kg and fluconazole at >or=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 >or=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.