Therapeutic efficacy of a liposomal formulation of amphotericin B (AmBisome) against murine blastomycosis

Abstract

The efficacy of a liposomal amphotericin B preparation (AmBisome) and a deoxycholate suspension (Fungizone) were compared in a pulmonary model of murine blastomycosis. Male, four-week-old CD-1 mice were infected intranasally with 19,400 or 27,450 cfu of viable Blastomyces dermatitidis yeasts and intravenous therapy begun 4 days later. Groups of ten mice were given various dosages of Fungizone or AmBisome or were untreated. All treatments were given 3 times per week for 2 weeks. Deaths were recorded over 49 days and the number of viable yeasts in the lungs of survivors quantitated by viable counting. Therapy with 1.0 mg/kg/dose of Fungizone or 1.0, 3.0, 5.0, 7.5 or 20.0 mg/kg/dose of AmBisome were equivalent and prolonged survival over controls and lower dosages of each drug. No acute or chronic toxicities were observed with any regimen. Quantitation of residual numbers of yeasts in the lung showed that 70-100% of mice given 7.5 mg/kg or greater of AmBisome were free of infection and were superior to other regimens. At equivalent 1.0 mg/kg dosages Fungizone was superior to AmBisome. Although AmBisome was three-fold less active than Fungizone on a dosage basis, higher curative doses could be given that were not toxic. These data indicate that AmBisome should be further tested in other models and in clinical trials.