Treatment of Experimental Invasive Aspergillosis with Novel Amphotericin B/Cholesterol-Sulfate Complexes

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Abstract
An immunosuppressed rabbit model of invasive aspergillosiswasused to evaluate a novel micellar preparation of cholesterol sulfate complexedto amphotericin B. The acute LD50 of amphotericin B-deoxycholate was 5.1 mg/kg versus 20 mg/kg for the amphotericin/cholesterol-sulfate complexes. Amphotericin B-deoxycholate giveniv at a dose of 1.5 mg/kg was more effective in sterilizing liver and kidney than the amphotericin/cholesterol sulfate complexes given iv at 1.5–4.5 mg/kg, but infection persisted in the lungs of all rabbits treated with those doses. Infection persisted even when the rabbits were given a lethal dose of amphotericin B-deoxycholate (4.5 mg/kg), but a dose of 15 mg/kg of the amphotericin/cholesterol-sulfate complexes sterilized tissues and was associated with no acute lethality. Equivalent doses of the amphotericin/cholesterol-sulfate complexes were less effective than amphotericin B-deoxycholate, but a fourfold decrease in acute lethality improved the therapeutic index of amphotericin B. The amphotericin/cholesterol-sulfate complexesappear to be an improvedmeans of amphotericin B delivery and may improve therapy for invasive aspergillosis.