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JAC Advance Access published online on September 27, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki343
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received April 28, 2005
Revised August 11, 2005
Accepted August 30, 2005

Original article

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

Russell E. Lewis 1 and Dimitrios P. Kontoyiannis 1*

1 University of Houston College of Pharmacy, Houston, TX, USA; Department of Infectious Diseases, Infection Control and Employee Health, Unit 402, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA

* To whom correspondence should be addressed.
Dimitrios P. Kontoyiannis, E-mail: dkontoyi{at}mdanderson.org


  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 in vitro and in vivo.

Keywords: aspergillosis; echinocandins; triazoles.
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