Caspofungin in combination with amphotericin B against Candida glabrata

Abstract

The effects of caspofungin combined with amphotericin B were investigated with Candida glabrata. Although in vitro experiments showed an indifferent interaction, the combination regimen was the only therapeutic approach yielding organ sterilization in a murine candidemia model.

FIG. 1.

Time-kill studies conducted with C. glabrata 4293. The dashed line represents a >99.9% growth reduction compared with the initial inoculum size. The limit of detection was 20 CFU/ml. Each data point represents the mean ± standard deviation for three independent experiments.

FIG. 2.

Kidney tissue burden of neutropenic CD1 mice. Study no. 1: panels A and B, the mice were infected intravenously with 2.6 × 10⁸ CFU/mouse of C. glabrata 4293, treated for six consecutive days with CAS at 0.3 or 1 mg/kg/day (Cas-0.3 and Cas-1), with AMB at 0.3 or at 1 mg/kg/day (Amb-0.3 and Amb-1), or with their respective combinations (Combo-0.3 and Combo-1). The mice were sacrificed on day 7 postinfection. Study no. 2: panel C, the mice were infected intravenously with 1.2 × 10⁸ CFU/mouse, treated daily with CAS at 3 mg/kg/day (Cas-3), with AMB at 3 mg/kg/day (Amb-3), or with their combination (Combo-3). Tissue burden experiments were performed on days 3, 5, and 7 postinfection, which corresponded to a total of 2, 4, and 6 days of therapy, respectively. The bars represent the medians. The asterisks at the bottom of panels A, B, and C indicate P values of <0.016.

FIG. 2.

Kidney tissue burden of neutropenic CD1 mice. Study no. 1: panels A and B, the mice were infected intravenously with 2.6 × 10⁸ CFU/mouse of C. glabrata 4293, treated for six consecutive days with CAS at 0.3 or 1 mg/kg/day (Cas-0.3 and Cas-1), with AMB at 0.3 or at 1 mg/kg/day (Amb-0.3 and Amb-1), or with their respective combinations (Combo-0.3 and Combo-1). The mice were sacrificed on day 7 postinfection. Study no. 2: panel C, the mice were infected intravenously with 1.2 × 10⁸ CFU/mouse, treated daily with CAS at 3 mg/kg/day (Cas-3), with AMB at 3 mg/kg/day (Amb-3), or with their combination (Combo-3). Tissue burden experiments were performed on days 3, 5, and 7 postinfection, which corresponded to a total of 2, 4, and 6 days of therapy, respectively. The bars represent the medians. The asterisks at the bottom of panels A, B, and C indicate P values of <0.016.

FIG. 2.

Kidney tissue burden of neutropenic CD1 mice. Study no. 1: panels A and B, the mice were infected intravenously with 2.6 × 10⁸ CFU/mouse of C. glabrata 4293, treated for six consecutive days with CAS at 0.3 or 1 mg/kg/day (Cas-0.3 and Cas-1), with AMB at 0.3 or at 1 mg/kg/day (Amb-0.3 and Amb-1), or with their respective combinations (Combo-0.3 and Combo-1). The mice were sacrificed on day 7 postinfection. Study no. 2: panel C, the mice were infected intravenously with 1.2 × 10⁸ CFU/mouse, treated daily with CAS at 3 mg/kg/day (Cas-3), with AMB at 3 mg/kg/day (Amb-3), or with their combination (Combo-3). Tissue burden experiments were performed on days 3, 5, and 7 postinfection, which corresponded to a total of 2, 4, and 6 days of therapy, respectively. The bars represent the medians. The asterisks at the bottom of panels A, B, and C indicate P values of <0.016.