AmBisome is a liposomal formulation of
amphotericin B that has broad-spectrum antifungal activity and greatly reduced toxicity compared to the parent
drug. In this study,
amphotericin B deoxycholate (
Fungizone) (1 mg/kg) and
AmBisome (1 to 20 mg/kg) were tested as single-dose prophylactic agents in both immunocompetent and immunosuppressed C57BL/6 mice challenged with either Candida albicans or Histoplasma capsulatum. Prophylactic efficacy was based on survival and fungal burden in the target organ (kidneys or spleen). At 9 to 10 days after histoplasma challenge, 80 to 90% of both immunocompetent and immunosuppressed mice in the control and
Fungizone groups had died. All
AmBisome-treated mice survived, although in the
AmBisome groups given 1 mg/kg, the mice became moribund by day 10 to 12. No spleen CFU were detected in the histoplasma-challenged mice given 10 or 20 mg of
AmBisome per kg. By 23 to 24 days after histoplasma challenge, fungal growth and/or death had occurred in all immunosuppressed mice except for four mice receiving 20 mg of
AmBisome per kg. There were still no detectable fungi in the spleens of immunocompetent mice given 10 or 20 mg of
AmBisome per kg. In the C. albicans experiment at 7 days postchallenge, all animals in both untreated and treated groups were alive with culture-positive kidneys. The kidney fungal burdens in
AmBisome groups given 5 to 20 mg/kg were at least 1 log unit lower than those in the
Fungizone group and significantly lower than those in the untreated control group (P < 0.05). There was a trend toward decreasing fungal growth in the kidneys as the dose of
AmBisome was increased. In conclusion, these results show that a single high dose of
AmBisome (5 to 20 mg/kg) had prophylactic efficacy in immunocompetent and immunosuppressed murine H. capsulatum and C. albicans models.