Comparison of a liposomal amphotericin B formulation (AmBisome) and deoxycholate amphotericin B (Fungizone) for the treatment of murine paracoccidioidomycosis

The therapeutic efficacy of a liposomal amphotericin B preparation (AmBisome), was compared with that of conventional amphotericin B deoxycholate suspension (Fungizone), in a murine model of acute pulmonary paracoccidioidomycosis. In two separate experiments, 21- to 24-day-old male BALB/c mice were infected intranasally with either 4·1 × 107 or 1·6 × 107 viable yeasts of Paracoccidioides brasiliensis isolate Gar and treated intravenously three times per week for 2 weeks with various doses of AmBisome, Fungizone, empty liposomes or no treatment. In the first study, 27 mg kg−1 of AmBisome improved survival over controls (P<0·05) and reduced lung burdens of P. brasiliensis over controls (P<0·01) or those treated with 1 mg kg−1 of AmBisome, but was equivalent to 1 mg kg−1 of Fungizone. Treatment with empty liposomes was equivalent to no treatment. In the second dose-escalating experiment, mice were treated with 0·6 mg kg−1 of Fungizone or 0·6, 5, 15 or 30 mg kg−1 of AmBisome. All regimens prolonged survival over controls (P<0·05–0·001). AmBisome at 5 mg kg−1 or greater reduced lung burdens of P. brasiliensis better than 0·6 mg kg−1 of Fungizone (P<0·001). AmBisome at 15 or 30 mg kg−1 cured 29% or 47% of the mice of infection; no other regimen effected a cure. Fungizone was >1- to <8-fold more efficacious on a milligram-per-kilogram basis, but at least 50-fold greater doses of AmBisome could be given safely that were curative. Further preclinical and clinical studies with AmBisome are indicated.