Efficacy of ravuconazole in treatment of mucosal candidosis in SCID mice.
A model of orogastric candidosis in SCID mice, which mimics disease seen in AIDS patients, was used to evaluate ravuconazole in comparison with fluconazole for treatment. Mice were infected orally with Candida albicans and received either no treatment or oral treatment once daily for 12 days with 1, 5, or 25 mg of ravuconazole per kg of body weight per day, 5 or 25 mg of fluconazole per kg per day, or diluent (10% dimethyl sulfoxide in 0.5% carboxymethyl cellulose). The numbers of C. albicans CFU in the esophagus, stomach, small intestine, and cecum on day 25 in mice given no treatment and diluent were equivalent. Both doses of fluconazole significantly reduced numbers of CFU in all four tissues but were equivalent to each other. Ravuconazole showed dose-responsive improvement of clearance of CFU. Ravuconazole at 25 mg/kg was superior in reduction of numbers of CFU in all tissues to controls or 25 mg of fluconazole per kg and to other regimens in at least three tissues. Fluconazole at 25 mg/kg cured no infection in any tissue, whereas 25 mg of ravuconazole/kg cleared infection in all tissues from 50% of mice. Ravuconazole has good efficacy and the potential to cure mucosal candidosis in the absence of a functional immune response.
Clemons
K V
KV
California Institute for Medical Research and Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center, San Jose, California 95128-2699, USA. clemons@cimr.org
Stevens
D A
DA
D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D002178:Candidiasis, Chronic Mucocutaneous / Q000188:drug therapy* / Q000382:microbiology; D004064:Digestive System / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D016513:Mice, SCID; D008826:Microbial Sensitivity Tests; D013844:Thiazoles / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
D000935:Antifungal Agents; D013844:Thiazoles; D014230:Triazoles; C104066:ER 30346