Treatment of experimental invasive aspergillosis with novel amphotericin b/cholesterol-sulfate complexes

An immunosuppressed rabbit model of invasive aspergillosiswasused to evaluate a novel micellar preparation of cholesterol sulfate complexedto amphotericin B. The acute LDso 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 wasmore effective in sterilizing liverand kidneythan the amphotericin/cholesterolsulfate 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 weregiven a lethal dose of amphotericin B-deoxycholate (4.5 mg/kg), but a dose of 15 mg/kg of the amphotericin/cholesterol-sulfate complexessterilized tissues and was associated with no acute lethality. Equivalent doses of the amphotericin/cholesterol-sulfate complexeswere lesseffectivethan amphotericin B-deoxycholate, but a fourfold decreasein acute lethality improvedthe therapeutic index of amphotericin B. The amphotericin/cholesterol-sulfate complexesappear to be an improvedmeans of amphotericin Bdeliveryand may improve therapy for invasive aspergillosis.