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.