Efficacies of two new antifungal agents, the triazole ravuconazole and theechinocandin LY-303366, in an experimental model of invasive aspergillosis

The efficacy of ravuconazole, a new triazole antifungal agent, and the echi nocandin LY-303366 were evaluated in an immunosuppressed, temporarily leuko penic rabbit model of invasive aspergillosis. Oral therapy with ravuconazol e at a dosage of 30 mg/kg of body weight per day or the echinocandin LY-303 366, given intravenously in a dosage of 5 or 10 mg/kg, was begun 24 h after a lethal or sublethal challenge, and results were compared with those for amphotericin B therapy and untreated controls. Prophylaxis was also studied with LY-303366 given at a dosage of 5 or 10 mg/kg/day 48 h before lethal o r sublethal challenge. Ravuconazole eliminated mortality, cleared aspergill us antigen from the serum, and eliminated Aspergillus fumigatus organisms f rom tissues of both lethally and sublethally challenged immunosuppressed an imals with invasive aspergillosis. Although LY-303366, at both doses, prolo nged survival and reduced aspergillus antigenemia, it did not eliminate asp ergillus organisms from organ tissues. The half-lives of ravuconazole and L Y-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation o f either drug was seen after 6 days of treatment. Although LY-303366 showed activity in this rabbit model of invasive aspergillosis, ravuconazole was the more active agent, comparable to amphotericin B. Additional studies are needed to determine the potential of ravuconazole for use in the treatment of this infection.