In vitro and in vivo activities of CS-758 (R-120758), a new triazole antifungal agent

Antimicrob Agents Chemother. 2002 Feb;46(2):367-70. doi: 10.1128/AAC.46.2.367-370.2002.

Abstract

The activity of CS-758 (R-120758), a new triazole antifungal agent, was evaluated and compared with those of fluconazole, itraconazole, and amphotericin B in vitro and with those of fluconazole and itraconazole in vivo. CS-758 exhibited potent in vitro activity against clinically important fungi. The activity of CS-758 against Candida spp. was superior to that of fluconazole and comparable or superior to those of itraconazole and amphotericin B. CS-758 retained potent activity against Candida albicans strains with low levels of susceptibility to fluconazole (fluconazole MIC, 4 to 32 microg/ml). Against Aspergillus spp. and Cryptococcus neoformans, the activity of CS-758 was at least fourfold superior to those of the other drugs tested. CS-758 also exhibited potent in vivo activity against murine systemic infections caused by C. albicans, C. neoformans, Aspergillus fumigatus, and Aspergillus flavus. The 50% effective doses against these infections were 0.41 to 5.0 mg/kg of body weight. These results suggest that CS-758 may be useful in the treatment of candidiasis, cryptococcosis, and aspergillosis.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use*
  • Aspergillus / drug effects
  • Candida / drug effects*
  • Cryptococcus neoformans / drug effects
  • Disease Models, Animal
  • Mice
  • Microbial Sensitivity Tests
  • Mycoses / drug therapy*
  • Treatment Outcome
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use

Substances

  • Antifungal Agents
  • Triazoles
  • R-120758