Voriconazole minimum inhibitory concentrations are predictive of treatment outcome in experimental murine infections by Candida glabrata

Abstract

In this study, 27 clinical isolates of Candida glabrata with voriconazole (VRC) minimum inhibitory concentrations (MICs) ranging from ≤0.03 μg/mL to 8 μg/mL were tested to determine whether in vitro data are predictive of in vivo efficacy. The efficacy of VRC administered at 40 mg/kg was assayed in a neutropenic murine model of disseminated infection by C. glabrata. The reduction in fungal tissue burden in the kidneys was used as a marker of treatment efficacy. VRC reduced the fungal tissue burden in mice infected with strains that had MICs below the epidemiological cut-off value (ECV) of 0.25 μg/mL. Variable efficacy of VRC was obtained when the MIC equalled the ECV, and VRC was ineffective when the MIC exceeded the ECV. These results suggest that the use of in vitro data could be useful to predict the outcome for infections by this fungus.

Keywords: Animal model; Antifungals; Candida glabrata; Epidemiological cut-off value; Fungal infection; Voriconazole.