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

L. K. Najvar, R. Bocanegra, N. P. Wiederhold, C. Lambros, N. Najarian, T. F. Patterson, J. R. Graybill

Research output: Contribution to journalArticle

19 Scopus citations

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 1day 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 ≥2.5mg/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.

Original languageEnglish (US)
Pages (from-to)595-600
Number of pages6
JournalClinical Microbiology and Infection
Volume14
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • Aminocandin
  • Antifungal prophylaxis
  • Candida albicans
  • Extended interval dosing
  • Invasive candidiasis
  • Mouse model

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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