Antifungal activities of D0870 against fluconazole-resistant Candida albicans.
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.
Kojima
M
M
Research Center, Mochida Pharmaceutical Co., Ltd., 722 Jimba-aza-Uenohara Gotemba, Shizuoka 412-8524, Japan.
Yamada
H
H
Nakamura
S
S
Kikuchi
M
M
Nakanishii
T
T
Takahashi
Y
Y
Mochizuki
H
H
Mikami
Y
Y
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*
D000935:Antifungal Agents; D014230:Triazoles; C058219:ICI 195739; D015725:Fluconazole