Effect of Ravuconazole, a New Triazole Antifungal, in a Rat Intraabdominal Abscess Model

Abstract

Background: Ravuconazole (BMS-207147) is a long-lasting triazole antifungal agent active against a broad spectrum of fungal pathogens including non-albicans Candida, Aspergillus, Cryptococcus and key dermatophytic fungi. Methods: The efficacy of ravuconazole was evaluated using an experimental intraabdominal abscess model in rats caused by Candida albicans (E81022). Two hundred milligrams of cyclophosphamide per kilogram was injected intraperitoneally into 40 rats. Four days (96 h) after the injection of cyclophosphamide, a mixture of C. albicans and autoclaved rat cecal contents [C. albicans 1.7 × 10⁸ colony-forming units/rat] was inoculated into the peritoneal cavity. The rats were divided into four groups: ravuconazole treated, fluconazole treated, itraconazole treated and untreated. Each antifungal was given orally at a dose of 10 mg/kg twice a day for 5 days. On the day after the last administration, the rats were dissected and the viable fungi in the abscesses were determined. The number of C. albicans in each abscess was determined by a quantitative culture technique. Results: Ravuconazole inhibited abscess formation and significantly decreased the viable cell counts in abscesses in comparison with the untreated group. It’s efficacy was at least equivalent to fluconazole and itraconazole against this pathogen. The rank order of potency (inhibition) was ravuconazole > itraconazole > fluconazole. Conclusion: Taking into consideration the antifungal spectrum of ravuconazole, which includes non-albicans Candida as well as C. albicans and Aspergillus, it is suggested that ravuconazole would be a good agent for the treatment of fungal peritonitis.