Micafungin activity against Candida albicans with diverse azole resistance phenotypes.
OBJECTIVE
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.
Richards
Theresa S
TS
Department of Global Health, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA.
Oliver
Brian G
BG
White
Theodore C
TC
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002177:Candidiasis / Q000382:microbiology; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000494:pharmacology*; D005656:Fungal Proteins / Q000096:biosynthesis; D018628:Gene Dosage; D006801:Humans; D055666:Lipopeptides; D008074:Lipoproteins / Q000494:pharmacology*; D000077551:Micafungin; D008826:Microbial Sensitivity Tests
D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D005656:Fungal Proteins; D055666:Lipopeptides; D008074:Lipoproteins; D000077551:Micafungin