title: Antifungal activities of D0870 against fluconazole-resistant Candida albicans.
abstract: We compared the in vitro and in vivo antifungal activities of D0870, a new triazole antifungal agent, with those of other antifungal agents against 8 clinical isolates of fluconazole-resistant Candida albicans. Microdilution testing was performed according to National Committee for Clinical Laboratory Standards (NCCLS) document M27-T. Minimal inhibitory concentration of D0870 (<0.004-1.0 micro g/ml) was lower than those of fluconazole (2->64 microEg/ml) and itraconazole (0.031-8.0 microEg/ml). In systemic infection models with C. albicans in normal and immunosuppressed mice, D0870 at 0. 3-30 mg/kg/day for 5 days after infection prolonged survival of the animals and showed the highest efficacy among the triazole antifungal agents. At pH 7 and 37C in Sabouraud dextrose broth (SDB), D0870 inhibited the growth of C. albicans and acted cytocidally against one of the middle-resistant strains. In an in vivo study against this strain, D0870 at 10 mg/kg/day for 5 days after infection significantly reduced kidney colony counts (2850+406-997+537 CFU/kidney, P<0.05) on day 7 after infection in comparison with those of the control mice at 24 h after infection. Plasma concentration of D0870 after a single oral administration at 10 mg/kg maintained a sufficient level for interpretation of in vivo antifungal activities. These results suggest that D0870 has strong antifungal activities against clinical isolates of fluconazole-resistant C. albicans in vitro and in vivo, and that these strong activities are at least partially concerned with the fungicidal action.
authors.affiliation: Research Center, Mochida Pharmaceutical Co., Ltd., 722 Jimba-aza-Uenohara Gotemba, Shizuoka 412-8524, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kojima
authors.forename: H
authors.initials: H
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: T
authors.initials: T
authors.lastname: Nakanishii
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Y
authors.initials: Y
authors.lastname: Mikami
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D004352:Drug Resistance, Microbial; D015725:Fluconazole / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C058219:ICI 195739; D015725:Fluconazole