JAC Advance Access first published online on April 23, 2008
This version published online on May 8, 2008
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkn156
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Original research |
Micafungin activity against Candida albicans with diverse azole resistance phenotypes
1 Department of Global Health, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA 2 Seattle Biomedical Research Institute, Seattle, WA, USA
Received 20 December 2007; returned 15 February 2008; revised 13 March 2008; accepted 16 March 2008
* Corresponding author. Tel: +1-206-256-7344; E-mail: ted.white{at}sbri.org
Objectives: The purpose of this study was to investigate whether mechanisms of azole resistance in Candida albicans contribute to reduced micafungin activity in vitro.
Methods: MICs were determined for a collection of strains with well-characterized mechanisms of azole resistance obtained from systemic, oral and vaginal infections. This collection of strains includes those with resistance-associated phenotypes. All known molecular mechanisms of azole resistance are included in this set of isolates (alone or in combination). Micafungin activity was further investigated for a subset of isolates by agar dilution.
Results: There was no correlation between any of the azole resistance mechanisms or resistance phenotypes and micafungin activity as determined by MIC, even in isolates with cross-resistance to multiple azole drugs. Overexpression of the ABC transporter CDR2 has been suggested to contribute to reduced echinocandin activity in agar dilution studies. By broth microdilution, there was no difference in MIC between the pump overexpressors and the collection as a whole. However, azole-resistant isolates from matched strains exhibited a small increase in their micafungin MICs relative to their susceptible controls. By agar dilution analysis, multiple CDR2-overexpressing strains exhibited reduced growth in the presence of micafungin relative to the laboratory strain SC5314.
Conclusions: Azole resistance mechanisms do not contribute to increased micafungin MIC as determined by broth microdilution. However, within sets of matched isolates, strains overexpressing CDR2 had a slight increase in micafungin MIC. Changes in micafungin susceptibility are associated with CDR2 overexpression in agar dilution tests.
Key Words: echinocandins , antifungals , XTT
The original version was incorrect. In the Abstract, first sentence of Conclusions, it should have read: ‘Azole resistance mechanisms do not contribute to increased micafungin MIC’.