In Vitro and In Vivo Efficacies of the New Triazole Albaconazole against Cryptococcus neoformans
AUTOR(ES)
Miller, J. L.
FONTE
American Society for Microbiology
RESUMO
The activity of albaconazole (UR-9825; J. Uriach & Cía. S.A., Barcelona, Spain) was compared to that of fluconazole against 12 isolates of Cryptococcus neoformans in vitro and against 1 isolate in vivo in a rabbit model of cryptococcal meningitis. Albaconazole was 100-fold more potent in vitro than fluconazole on a per-weight basis and was fungicidal at potentially relevant concentrations for two isolates. MICs ranged from ≤0.0012 to 1.25 μg/ml, with the MICs for most isolates being between 0.039 and 0.156 μg/ml. Isolates were from human immunodeficiency virus (HIV)-infected and non-HIV-infected patients and were of serotypes A, B, and C; and the fluconazole MICs for some of the isolates were elevated. Infected rabbits were treated with either fluconazole or albaconazole at dosages ranging from 5 to 80 mg/kg of body weight/day. The peak concentrations of albaconazole in serum and cerebrospinal fluid (CSF) averaged 4.14 and 0.62 μg/ml, respectively, in animals receiving 80 mg/kg/day. Comparison of the concentrations in serum and CSF suggested a level of CSF penetration of approximately 15%. Despite limited penetration into the subarachnoid space, at all three doses tested albaconazole was as effective as fluconazole for the treatment of cryptococcal meningitis in rabbits.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=321550Documentos Relacionados
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