Treatment of murine cryptococcal meningitis with UR-9751 and UR-9746

In these studies, we compare the efficacy of two new azole antifungals with fluconazole in a murine model of cryptococcal meningitis. Mice were infected intracranially. Beginning one day later, groups of 7–10 mice were treated through to day 10 orally with UR-9751 or UR-9746 at 0·1, 0·25, 0·5, 1 or 10 mg kg−1 day−1 or fluconazole at 10 mg kg−1 day−1. At 10 mg kg−1 day−1, all three drugs prolonged survival over controls, but at 1 mg kg−1 day−1, only UR-9746 prolonged survival. Tissue counts were more varied on mice sacrificed 8 days after infection. In general, both UR drugs were equal or more potent than fluconazole, and UR-9751 was more effective than UR-9746.