In this study,
oral administration of the
triazole D0870 was compared to
oral administration of
fluconazole in the treatment of experimental vaginal
candidiasis. With an
estrogen-dependent murine model of Candida albicans vaginal
infection, the effects of
D0870 on several isolates, including
fluconazole-susceptible and -resistant isolates, were tested.
D0870, at doses of 0.5 and 2.5 mg/kg of
body weight given once over the course of a 10-day
infection, was effective in eradicating
vaginitis caused by
fluconazole-susceptible laboratory and clinical isolates, respectively. In contrast, a stricter treatment regimen (every 24 to 48 h) with 10 and 25 mg of
fluconazole per kg was required to achieve similar reductions in vaginal fungal titers induced by the same isolates. Whereas
fluconazole was consistently ineffective in
infections induced by
fluconazole-resistant isolates, as predicted by in vitro susceptibility tests,
D0870 was effective, although a daily regimen of 25 mg/kg was required. Additional studies showed that despite the in vitro activity of
D0870 against two clinical Candida glabrata isolates, neither
D0870 nor
fluconazole was effective at daily doses as high as 100 and 125 mg/kg, respectively. Taken together, although
D0870 failed to show efficacy against experimental C. glabrata
vaginitis,
D0870 was superior to
fluconazole in the treatment of experimental C. albicans
vaginitis caused by isolates that were either susceptible or resistant to
fluconazole.