Therapeutic and prophylactic efficacy of aminocandin (IP960) against disseminated candidiasis in mice

Clin Microbiol Infect. 2008 Jun;14(6):595-600. doi: 10.1111/j.1469-0691.2008.01994.x. Epub 2008 Apr 5.

Abstract

Extended interval dosing of the echinocandins has been suggested as a potential strategy to overcome the need for daily intravenous administration. This study evaluated the therapeutic and prophylactic efficacy of single doses of aminocandin, a new echinocandin in preclinical development, in a murine model of invasive candidiasis. For therapy, groups of mice were infected with Candida albicans, followed by a single dose of aminocandin (1-15 mg/kg) or placebo (mannitol 5% w/v) administered 1 day after inoculation. As prophylaxis, mice were given a single dose (5 or 30 mg/kg) of aminocandin, caspofungin, or placebo at increasing intervals between dose and inoculation. In both treatment and prophylaxis studies, survival was assessed at 21 days post-inoculation. The reduction in fungal burden was assessed in kidney tissue on day 8 post-inoculation. For treatment, single doses of aminocandin of >/=2.5 mg/kg prolonged survival significantly. In addition, the two doses evaluated for reductions in fungal burden (5 and 15 mg/kg) revealed fungicidal activity. As prophylaxis, both aminocandin and caspofungin 5 and 30 mg/kg prolonged survival when given 7 days before inoculation. Aminocandin and caspofungin 30 mg/kg were both able to prolong survival when the interval between dose and inoculation was increased to 10 days. When this interval was extended to 14 days, only aminocandin 30 mg/kg prolonged survival and reduced fungal burden. These results demonstrate that single doses of aminocandin are effective as treatment and prophylaxis, and suggest that extended interval dosing may be a useful strategy for treating invasive candidiasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / therapeutic use*
  • Candida albicans / drug effects
  • Candidiasis / drug therapy*
  • Candidiasis / prevention & control*
  • Caspofungin
  • Colony Count, Microbial
  • Disease-Free Survival
  • Echinocandins / administration & dosage
  • Echinocandins / therapeutic use
  • Kidney / microbiology
  • Lipopeptides
  • Lipoproteins / administration & dosage
  • Lipoproteins / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred ICR

Substances

  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Lipoproteins
  • aminocandin
  • Caspofungin