Efficacy of caspofungin against Aspergillus flavus, Aspergillus terreus, and Aspergillus nidulans

Abstract

The echinocandin caspofungin is a potent inhibitor of the activity of 1,3-beta-D-glucan synthase from Aspergillus flavus, Aspergillus terreus, and Aspergillus nidulans. In murine models of disseminated infection, caspofungin prolonged survival and reduced the kidney fungal burden. Caspofungin was at least as effective as amphotericin B against these filamentous fungi in vivo.

FIG. 1.

Survival of mice infected with A. flavus, A. terreus, or A. nidulans. Therapy (1, 0.5, 0.25, 0.125, or 0.06 mg/kg CAS or 1 mg/kg AMB administered i.p. once daily) was initiated immediately after infection and was continued for 7 days. Survival was monitored for 28 days, and Kaplan-Meier plots were generated. A. nidulans-infected mice remained immunosuppressed throughout the study. There were 10 mice in each group. *, P ≤ 0.05; mpk, milligram per kilogram.

FIG. 2.

Reduction of kidney burden in mice infected with A. flavus, A. terreus, or A. nidulans and treated with CAS or AMB. Infected mice were treated with vehicle or drug (CAS or AMB; 1, 0.5, 0.25, 0.125, 0.06, or 0.03 mg/kg per day administered i.p. once daily), and the kidney fungal burden at 7 days postinfection was determined by qPCR. The mean burdens (log₁₀ conidial equivalents/g kidney ± standard error) for vehicle-treated animals were as follows: A. flavus, 6.70 ± 0.15; A. terreus, 6.72 ± 0.17; A. nidulans, 5.68 ± 0.19. For each drug-treated group, the reduction in the mean burden (± standard error) relative to that in mice that received vehicle treatment is given. Values were derived from 10 mice per therapy group except when specified by numbers within or just above or below the bars. The y-axis scale for the A. flavus plot is different from those for A. terreus and A. nidulans. *, P ≤ 0.05; mpk, milligram per kilogram.