Efficacy of fluconazole in experimental invasive aspergillosis

The efficacy of fluconazole against Aspergillus fumigatus was evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Fluconazole was given at a dosage of 60 mg/kg twice daily and was compared with amphotericin B given intravenously at a dosage of 1.5 mg/(kg.d). Fluconazole reduced the tissue burden of Aspergillus from that in untreated controls by 10- to 100-fold in liver, kidney, and lung. However, at these doses amphotericin B was more effective in sterilizing tissues and in reducing the tissue burden of Aspergillus in those organs. Both fluconazole and amphotericin B decreased or eliminated circulating Aspergillus antigen and improved survival over that of untreated controls. Thus fluconazole shows activity in this rabbit model of invasive aspergillosis and should be further evaluated for use in the treatment of this disease.