Comparison of fluconazole and amphotericin B for prevention and treatment of experimental Candida endocarditis

Abstract

Fluconazole and amphotericin B were compared in the prophylaxis and treatment of Candida albicans aortic endocarditis in a rabbit model. In the prophylaxis study, catheterized rabbits received, prior to intravenous (i.v.) challenge with C. albicans (2 x 10(7) blastospores), either no therapy, single-dose i.v. amphotericin B (1 mg/kg of body weight), single-dose fluconazole (50 mg/kg or 100 mg/kg i.v. or intraperitoneally [i.p.]), or fluconazole (50 mg/kg or 100 mg/kg i.v. or i.p.) with a second dose 24 h after inoculation. A single dose of amphotericin B was significantly more effective than either the one- or two-dose regimens of fluconazole at both 50 mg/kg (P less than 0.001 and P less than 0.03, respectively) and 100 mg/kg (P less than 0.01 and P less than 0.001, respectively) in the prevention of C. albicans endocarditis. In parallel treatment studies of established C. albicans endocarditis, i.v. amphotericin B (1 mg/kg) or i.p. fluconazole (50 mg/kg) was begun 24 or 60 h postinfection and continued daily for 9 or 12 days. At these dose regimens, amphotericin B was consistently more effective than fluconazole in reducing fungal vegetation densities, regardless of the timing of initiation of therapy. We also examined the efficacy of fluconazole at a daily dose of 100 mg/kg i.p. administered for 21 days in the treatment of established C. albicans endocarditis. When therapy was continued for 2 weeks or longer, fluconazole was more effective than no drug and approximately twice as effective as 12 days of amphotericin B in reducing intravegetation fungal densities. Our results suggest that amphotericin B is superior to fluconazole in both the prophylaxis and treatment of C. albicans endocarditis in the rabbit model. These findings may relate to the predominantly fungistatic activity of fluconazole against C. albicans in vitro.