Effects of caspofungin against Candida guilliermondii and Candida parapsilosis

Abstract

The in vitro activity of caspofungin (CAS) was investigated against 28 yeast isolates belonging to Candida albicans (n = 5), Candida guilliermondii (n = 10), and Candida parapsilosis (n = 13). CAS MICs obtained by broth dilution and Etest methods clearly showed a rank order of susceptibility to the echinocandin compound with C. albicans > C. parapsilosis > C. guilliermondii. Similarly, time-kill assays performed on selected isolates showed that CAS was fungistatic against C. albicans and C. parapsilosis, while it did not exert any activity against C. guilliermondii. In a murine model of systemic candidiasis, CAS given at doses as low as 1 mg/kg of body weight/day was effective at reducing the kidney burden of mice infected with either C. albicans or C. guilliermondii isolates. Depending on the isolate tested, mice infected with C. parapsilosis responded to CAS given at 1 and/or 5 mg/kg/day. However, the overall CFU reduction for C. guilliermondii and C. parapsilosis was approximately 100-fold less than that for C. albicans. Our study shows that CAS was active in experimental systemic candidiasis due to C. guilliermondii and C. parapsilosis, but this activity required relatively high drug dosages.

FIG.1.

Time-kill studies conducted with C. albicans SC5314, C. guilliermondii(isolates 1, 2, and 3), and C. parapsilosis isolates. (isolates 1, 2, and 3). Black diamonds, controls; closed squares, 1× AMB MIC; open squares, 8× AMB MIC; closed triangles, 1× CAS MIC; open triangles, 8× CAS MIC. The dotted lines represent a ≥99.9% growth reduction compared with the initial inoculum size (fungicidal effect). The limit of detection is 20 CFU/ml. Each data point represents the mean ± standard deviation (error bar) for three independent experiments.

FIG.1.

Time-kill studies conducted with C. albicans SC5314, C. guilliermondii(isolates 1, 2, and 3), and C. parapsilosis isolates. (isolates 1, 2, and 3). Black diamonds, controls; closed squares, 1× AMB MIC; open squares, 8× AMB MIC; closed triangles, 1× CAS MIC; open triangles, 8× CAS MIC. The dotted lines represent a ≥99.9% growth reduction compared with the initial inoculum size (fungicidal effect). The limit of detection is 20 CFU/ml. Each data point represents the mean ± standard deviation (error bar) for three independent experiments.

FIG.1.

Time-kill studies conducted with C. albicans SC5314, C. guilliermondii(isolates 1, 2, and 3), and C. parapsilosis isolates. (isolates 1, 2, and 3). Black diamonds, controls; closed squares, 1× AMB MIC; open squares, 8× AMB MIC; closed triangles, 1× CAS MIC; open triangles, 8× CAS MIC. The dotted lines represent a ≥99.9% growth reduction compared with the initial inoculum size (fungicidal effect). The limit of detection is 20 CFU/ml. Each data point represents the mean ± standard deviation (error bar) for three independent experiments.

FIG.1.

Time-kill studies conducted with C. albicans SC5314, C. guilliermondii(isolates 1, 2, and 3), and C. parapsilosis isolates. (isolates 1, 2, and 3). Black diamonds, controls; closed squares, 1× AMB MIC; open squares, 8× AMB MIC; closed triangles, 1× CAS MIC; open triangles, 8× CAS MIC. The dotted lines represent a ≥99.9% growth reduction compared with the initial inoculum size (fungicidal effect). The limit of detection is 20 CFU/ml. Each data point represents the mean ± standard deviation (error bar) for three independent experiments.

FIG.2.

Kidney fungal burden of CD1 mice. In studies involving isolates of C. guilliermondii and C. parapsilosis, the mice were rendered neutropenic. Animals were treated daily for 4 consecutive days with AMB at 1 mg/kg/day (AMB 1) and CAS at 0.25, 1, or 5 mg/kg/day (CAS 0.25, CAS 1, and CAS 5, respectively). Tissue burden experiments were performed on day 5 postinfection. The bars represent the medians. The asterisks at the bottom of panels indicate that the values were significantly different (P values of <0.05) from the values for the controls (C).

FIG.2.

Kidney fungal burden of CD1 mice. In studies involving isolates of C. guilliermondii and C. parapsilosis, the mice were rendered neutropenic. Animals were treated daily for 4 consecutive days with AMB at 1 mg/kg/day (AMB 1) and CAS at 0.25, 1, or 5 mg/kg/day (CAS 0.25, CAS 1, and CAS 5, respectively). Tissue burden experiments were performed on day 5 postinfection. The bars represent the medians. The asterisks at the bottom of panels indicate that the values were significantly different (P values of <0.05) from the values for the controls (C).

FIG.2.

Kidney fungal burden of CD1 mice. In studies involving isolates of C. guilliermondii and C. parapsilosis, the mice were rendered neutropenic. Animals were treated daily for 4 consecutive days with AMB at 1 mg/kg/day (AMB 1) and CAS at 0.25, 1, or 5 mg/kg/day (CAS 0.25, CAS 1, and CAS 5, respectively). Tissue burden experiments were performed on day 5 postinfection. The bars represent the medians. The asterisks at the bottom of panels indicate that the values were significantly different (P values of <0.05) from the values for the controls (C).

FIG.2.

Kidney fungal burden of CD1 mice. In studies involving isolates of C. guilliermondii and C. parapsilosis, the mice were rendered neutropenic. Animals were treated daily for 4 consecutive days with AMB at 1 mg/kg/day (AMB 1) and CAS at 0.25, 1, or 5 mg/kg/day (CAS 0.25, CAS 1, and CAS 5, respectively). Tissue burden experiments were performed on day 5 postinfection. The bars represent the medians. The asterisks at the bottom of panels indicate that the values were significantly different (P values of <0.05) from the values for the controls (C).