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Antimicrobial Agents and Chemotherapy, February 2003, p. 601-606, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.601-606.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Efficacy of CS-758, a Novel Triazole, against Experimental Fluconazole-Resistant Oropharyngeal Candidiasis in Mice

Yasuki Kamai,1* Mikie Kubota,1 Takashi Fukuoka,1 Yoko Kamai,2 Naoyuki Maeda,2 Tsunemichi Hosokawa,2 Takahiro Shibayama,3 Katsuhisa Uchida,4 Hideyo Yamaguchi,4 and Shogo Kuwahara5

Biological Research Laboratories,1 Laboratory Animal Science and Toxicology Research Laboratories,2 Pharmacokinetics and Drug Delivery Research Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo 140-8710,3 Teikyo University Institute of Medical Mycology, Hachioji, Tokyo 192-0395,4 Toho University School of Medicine, Ohta-ku, Tokyo 143-8540, Japan5

Received 8 July 2002/ Returned for modification 21 August 2002/ Accepted 21 October 2002

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 µg/ml) against the strains used in this murine model including fluconazole-susceptible dose-dependent and fluconazole-resistant strains (fluconazole MICs, 16 to 64 µg/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 µg/ml). These results suggest that CS-758 is a promising compound for the treatment of oropharyngeal candidiasis including fluconazole-refractory infections.

* Corresponding author. Mailing address: Biological Research Laboratories, Sankyo Co., Ltd., 2-58 Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. Phone: 81-3-3492-3131. Fax: 81-3-5436-8565. E-mail: ykamai{at}shina.sankyo.co.jp.

Antimicrobial Agents and Chemotherapy, February 2003, p. 601-606, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.601-606.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kamai, Y., Kakuta, M., Shibayama, T., Fukuoka, T., Kuwahara, S. (2005). Antifungal Activities of R-135853, a Sordarin Derivative, in Experimental Candidiasis in Mice. Antimicrob. Agents Chemother. 49: 52-56 [Abstract] [Full Text]  


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