Antifungal activity of amphotericin B-lipid admixtures in experimental systemic candidosis in naive mice

We have shown previously that admixtures of amphotericin B (AMB) and Intral ipid (AMB-IL) obtained by vigorous and prolonged agitation are stable and c an be standardized. These preparations exhibited in-vitro activity against various Candida spp., and had significantly lower toxicity. The present stu dy was undertaken to evaluate the activity of AMB-IL admixtures in vivo in comparison with the conventional formulation of AMB (Fungizone), using a mu rine model of experimental systemic candidosis. ICR female mice (4-6 weeks old) were injected iv with 5 x 10(4) Candida albicans CBS 562. The animals developed a lethal infection (100%) within 10 days. Systemic candidosis was demonstrated by the presence of fungal elements in kidneys and spleen tiss ue, and by enumeration of cfu of Candida in the tissue homogenates. AMB-IL or AMB was administered iv 48 h post-Candida inoculation for 5 consecutive days. Four experiments with 108 mice treated with AMB 5 x 0.4 mg/kg and fol lowed up for 6 weeks, showed that the mean survival percentages at the end of the experiment were 0, 24.9 and 52.5% for the untreated group, conventio nal AMB-treated and AMB-IL-treated groups, respectively. The mean survival time (MST) was 7.4, 25 and 30 days for the untreated, conventional AMB-trea ted and AMB-IL-treated groups, respectively. Use of increased doses of AMB showed that conventional AMB at doses greater than 5 x 1 mg/kg caused immed iate animal death. AMB-IL was used at doses of AMB up to 5 x 2 mg/kg. Exper iments with 104 mice revealed that the mean survival percentage at the end of the experiment was 0, 34.5, 58.6 and 97% for the untreated, conventional AMB-treated (5 x 1 mg/kg), AMB-IL-l-treated (5 x 1 mg/kg) and AMB-IL-P-tre ated (5 x 2 mg/kg) groups, respectively. The MST was 7, 27.8, 34.8 and 41.4 days for the untreated, conventional AMB-treated, AMB-IL-1-treated and AMB -IL-2-treated groups, respectively. The results of this study reveal that A MB-IL is significantly more effective in treating systemic murine candidosi s than conventional AMB.