Wild-Type MIC Distributions and Epidemiologic Cutoff Values for Fluconazole and Candida: Time for New Clinical Breakpoints?

Abstract

Antifungal susceptibility testing of Candida against fluconazole has been standardized by both the Clinical and Laboratory Standards Institute (CLSI) and the European
Committee on Antimicrobial Susceptibility Testing (EUCAST). Both CLSI and EUCAST have developed clinical breakpoint (CBP)
criteria for fluconazole, but these differ in both magnitude and target species. Studies using the EUCAST method have also
defined wild-type minimum inhibitory concentration (MIC) distributions and epidemiologic cutoff values (ECVs or ECOFFs) for
the common species of Candida. The ECVs serve as a sensitive means of discriminating wild-type strains from those with acquired resistance mechanisms and
include MICs of 1μg/mL for C. albicans, 2μg/mL for C. tropicalis and C. parapsilosis, 32μg/mL for C. glabrata, and 128μg/mL for C. krusei. Because the CLSI CBPs may be too insensitive to detect emerging resistance among strains of C. albicans, C. tropicalis, and C. parapsilosis, and bisect the WT MIC distribution of C. glabrata, we sought to establish the wild-type MIC distribution and ECVs for fluconazole and Candida spp. The establishment of the wild-type MIC distributions and ECVs for fluconazole using CLSI methods will be useful in resistance
surveillance and may prove to be an important step in the development of species-specific CBPs for this important antifungal
agent.

KeywordsAntifungal susceptibility testing-Fluconazole-Epidemiologic cutoff values-Clinical breakpoints-
Candida