title: Efficacy of CS-758, a novel triazole, against experimental fluconazole-resistant oropharyngeal candidiasis in mice.
abstract: The therapeutic efficacy of CS-758, a novel triazole, was evaluated against experimental murine oropharyngeal candidiasis induced by Candida albicans with various susceptibilities to fluconazole. Against infections induced by strains with various susceptibilities to fluconazole, the efficacy of fluconazole was strongly correlated with the MIC of fluconazole, as measured by the NCCLS method, and agreed with the NCCLS interpretive breakpoints, suggesting that the efficacies of new drugs could be predicted by using this model. The results of the fungal burden study corresponded with the results of the histopathological study. CS-758 exhibited potent in vitro activity (MICs, 0.004 to 0.06 micro g/ml) against the strains used in this murine model including fluconazole-susceptible dose-dependent and fluconazole-resistant strains (fluconazole MICs, 16 to 64 micro g/ml). CS-758 exhibited excellent efficacy against the infections induced by all the strains including a fluconazole-resistant strain, and the reductions in viable cell counts were significant at 10 and 50 mg/kg of body weight/dose. Fluconazole was not effective even at 50 mg/kg/dose against infections induced by a fluconazole-resistant strain (fluconazole MIC, 64 micro g/ml). These results suggest that CS-758 is a promising compound for the treatment of oropharyngeal candidiasis including fluconazole-refractory infections.
authors.affiliation: Biological Research Laboratories, Laboratory Animal Science and Toxicology Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710, Japan. ykamai@shina.sankyo.co.jp
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kamai
authors.forename: Mikie
authors.initials: M
authors.lastname: Kubota
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukuoka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kamai
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Maeda
authors.forename: Tsunemichi
authors.initials: T
authors.lastname: Hosokawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shibayama
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Uchida
authors.forename: Hideyo
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Shogo
authors.initials: S
authors.lastname: Kuwahara
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002177:Candidiasis / Q000188:drug therapy* / Q000473:pathology; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009960:Oropharynx / Q000187:drug effects / Q000382:microbiology; D014059:Tongue / Q000473:pathology; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C453343:R-120758; D015725:Fluconazole