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Echinocandin-Resistant Candida: Molecular Methods and Phenotypes

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Abstract

We now have a decade of experience with echinocandin drugs. Large-scale epidemiologic antifungal surveillance studies have demonstrated that caspofungin, micafungin, and anidulafungin retain high potency on clinical isolates of Candida, and resistance remains relatively low. Yet reports of breakthrough infections involving strains with a high minimum inhibitory concentration (MIC) are mounting. Mechanism-specific resistance involving amino acid substitutions in the Fks subunit(s) of the drug target glucan synthase results in reduced enzyme sensitivity to drug and high MICs. The mechanism affects all three drugs and is encountered in all Candida species, as well as in Aspergillus. An initial susceptibility testing breakpoint failed to adequately distinguish wild-type susceptible isolates from fks mutant resistant strains. Considering data from epidemiologic, microbiologic, pharmacokinetic/pharmacodynamic, biochemical, and genetic studies that better capture resistant isolates with fks genotypes has resulted in a proposed new breakpoint which provides a more reliable measure of probable therapeutic success.

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Acknowledgments

Studies on echinocandin drugs in the Perlin lab are supported by grants from the National Institutes of Health (AI069397), Merck, Pfizer, and Astellas. I want to thank Steven Park and Yanan Zhao for their contributions to the preparation of the manuscript.

Disclosure

Conflicts of Interest: Dr. Perlin serves on advisory and opinion leader boards for Merck, Pfizer, and Astellas, and he also receives grant support from these companies.

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  1. Public Health Research Institute, New Jersey Medical School-UMDNJ, 225 Warren Street, Newark, NJ, 07103, USA

    David S. Perlin

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Correspondence to David S. Perlin.

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Perlin, D.S. Echinocandin-Resistant Candida: Molecular Methods and Phenotypes. Curr Fungal Infect Rep 5, 113–119 (2011). https://doi.org/10.1007/s12281-011-0054-x

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