In vitro activity of a Hos2 deacetylase inhibitor, MGCD290, in combination with echinocandins against echinocandin-resistant Candida species.

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ID: 2999
2015
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Abstract
MGCD290, a Hos2 fungal histone deacetylase inhibitor, showed modest activity when tested alone (MIC range, 0.12-4 μg/mL; MIC50/90, 0.5/4 μg/mL) against Candida glabrata (n=15; 14 fks mutants; 5 also fluconazole resistant), Candida albicans (8 fks mutants; 2 also fluconazole resistant), Candida tropicalis (4 fks mutants), and Candida krusei (3 fks mutants). However, MGCD290 showed synergy or partial synergy for 33.3%, 30.1%, 36.7%, and 80.0% of the isolates when tested with anidulafungin, caspofungin, micafungin, and fluconazole, respectively. Favorable interactions were achieved with low concentrations of MGCD290 (0.015-0.25 μg/mL), and categorical shifts were observed in 2 of 8 (25.0%) isolates of C. albicans and 2 of 3 (66.7%) isolates of C. krusei and in 4 of the 5 (80.0%) fluconazole-resistant isolates of C. glabrata. MGCD290 exerts a distinctly favorable influence on the MICs of fluconazole and the echinocandins, resulting in conversion from resistance to susceptibility regardless of fks mutations.
Reference Key
pfaller2015indiagnostic Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Pfaller, M A;Rhomberg, P R;Messer, S A;Castanheira, M;
Journal Diagnostic microbiology and infectious disease
Year 2015
DOI
10.1016/j.diagmicrobio.2014.11.008
URL
Keywords Keywords not found

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