Efficacy of caspofungin against Aspergillus terreus

Abstract

We investigated the in vitro and in vivo activities of caspofungin against Aspergillus terreus. The drug increased survival and reduced tissue fungal burden in neutropenic mice. Therefore, our data support the role of caspofungin in treating systemic infections due to this emerging pathogen.

FIG. 1.

Survival of mice infected intravenously with approximately 5 × 10⁵ conidia per mouse of two strains of A. terreus. Both studies were conducted by initiating the therapy 3 h postinfection (day 0) and continued through day 9 postinfection (10 consecutive days). There were 10 mice in each group, with the exception of the control group and the group of mice treated with CAS at 1 mg/kg/day in studies with A. terreus 1 containing 35 and 20 mice, respectively. Asterisks indicate groups with prolonged survival over controls (P, <0.05).

FIG. 2.

Tissue burden of neutropenic CD1 mice. The mice were infected intravenously with approximately 5 × 10⁵ conidia of A. terreus 1 and treated with CAS administrated i.p. at doses of 1 and 5 mg/kg/day. The therapy was initiated 3 h postinfection and administrated daily from day 0 to day 4 (5 consecutive days), and the mice were sacrificed on day 5 postinfection (24 h after the last dose). Total brain (A) and kidney (B) tissue fungal burden was expressed as log₁₀ of total CFU. The bars represent the medians. Asterisks indicate groups with tissue burden counts lower than control (P, <0.05).

FIG. 3.

CAS plasma levels. Plasma sampling was performed after 1 day and 5 consecutive days of CAS therapy at 1 mg/kg/day (gray column) and 5 mg/kg/day (white column). Blood samples were drawn at 2 h postdose. Values represent the mean concentrations plus or minus standard deviations of seven mice per group.