Micafungin in combination with voriconazole in Aspergillus species: A pharmacodynamic approach for detection of combined antifungal activity in vitro

Abstract

Objectives: Preclinical and clinical evidence indicate that echinocandin-triazole combinations provide enhanced killing versus triazoles alone against some Aspergillus isolates, however, in vitro test results designed to detect this combined effect are difficult to interpret. Methods: We used a straightforward pharmacodynamic approach based on a microdilution format and a colorimetric analysis to harmonize growth end points. Results: We detected a fourfold decrease in the EC90 of voriconazole when tested in combination with micafungin (4 mg/L) against isolates of Aspergillus fumigatus and Aspergillus terreus, but not against an isolate of Aspergillus flavus. Echinocandin-enhanced voriconazole activity was confirmed in A. fumigatus and A. terreus but not A. flavus by fluorescent morbidity staining and fluorescence microscopic analysis of damaged hyphae. Conclusions: A microdilution based pharmacodynamic method for testing antifungal combinations provides a less ambiguous description of the combined effects of antifungals against moulds and could be useful in reference laboratories that routinely evaluate the activity of antifungal combinations n vitro and in vivo. © The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.