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.
Restrepo
M I
MI
University of Texas Health Science Center at San Antonio, 78284, USA.
Najvar
L K
LK
Barchiesi
F
F
Luther
M F
MF
Graybill
J R
JR
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003455:Cryptococcus neoformans / Q000187:drug effects*; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D016919:Meningitis, Cryptococcal / Q000188:drug therapy*; D051379:Mice; D008826:Microbial Sensitivity Tests; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
D000935:Antifungal Agents; D009025:Morpholines; D014230:Triazoles; C104730:UR 9746; C104729:UR 9751; D015725:Fluconazole