Journal of Antimicrobial Chemotherapy (1999) 44, 787-790
© 1999 The British Society for Antimicrobial Chemotherapy
Antifungal activity of amphotericin B–lipid admixtures in experimental systemic candidosis in naive mice
Department of Human Microbiology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
We have shown previously that admixtures of amphotericin B (AMB) and Intralipid (AMB–IL) obtained by vigorous and prolonged agitation are stable and can be standardized. These preparations exhibited in-vitro activity against various Candida spp., and had significantly lower toxicity. The present study was undertaken to evaluate the activity of AMB–IL admixtures in vivo in comparison with the conventional formulation of AMB (Fungizone), using a murine model of experimental systemic candidosis. ICR female mice (4–6 weeks old) were injected iv with 5 x 104 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 tissue, 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 followed 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, conventional 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-treated 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 immediate animal death. AMB–IL was used at doses of AMB up to 5 x 2 mg/kg. Experiments 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-1-treated (5 x 1 mg/kg) and AMB–IL-2-treated (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 AMB–IL is significantly more effective in treating systemic murine candidosis than conventional AMB.
* Corresponding author. Tel: +972-3-6409069 or +972-3-6409870; Fax: 972-3-6409160; E-mail: segale{at}post.tau.ac.il
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