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Antimicrobial Agents and Chemotherapy, December 2000, p. 3381-3388, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Efficacies of Two New Antifungal Agents, the Triazole Ravuconazole and the Echinocandin LY-303366, in an Experimental Model of Invasive Aspergillosis

Jenna Roberts, Kathleen Schock, Susan Marino, and Vincent T. Andriole*

Section of Infectious Diseases, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06520

Received 17 July 2000/Returned for modification 23 August 2000/Accepted 14 September 2000

The efficacy of ravuconazole, a new triazole antifungal agent, and the echinocandin LY-303366 were evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Oral therapy with ravuconazole at a dosage of 30 mg/kg of body weight per day or the echinocandin LY-303366, 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 or sublethal challenge. Ravuconazole eliminated mortality, cleared aspergillus antigen from the serum, and eliminated Aspergillus fumigatus organisms from tissues of both lethally and sublethally challenged immunosuppressed animals with invasive aspergillosis. Although LY-303366, at both doses, prolonged survival and reduced aspergillus antigenemia, it did not eliminate aspergillus organisms from organ tissues. The half-lives of ravuconazole and LY-303366 in rabbits were 13 and 12.5 h, respectively, and no accumulation of 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.

* Corresponding author. Mailing address: Infectious Disease Section, Department of Medicine, Yale University School of Medicine, 201-202 LCI, 333 Cedar St., P.O. Box 208022, New Haven, CT 06520. Phone: (203) 785-4141. Fax: (203) 785-6179. E-mail: vincent.andriole{at}yale.edu.

Antimicrobial Agents and Chemotherapy, December 2000, p. 3381-3388, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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