Wild-Type MIC Distributions and Epidemiological Cutoff Values for Posaconazole and Voriconazole and Candida spp. as Determined by 24-Hour CLSI Broth Microdilution

Abstract

In the absence of clinical breakpoints (CBPs) for posaconazole, these WT distributions and ECVs will be useful in surveillance for emergence of reduced susceptibility to posaconazole among Candida spp. Whereas a CBP for susceptibility of <1 g/ml has been established for voriconazole and all species of Candida, it is notable that ECVs for this agent range from 10-to >100-fold lower than the CBP, depending on the species of Candida. The CBP is inadequate in detecting the emergence of voriconazole resistance among most Candida species encountered clinically. The CBPs for voriconazole should be reassessed, with consideration for development of species-specific CBPs.

Comparison of the Broth Microdilution (BMD) Method of the European Committee on Antimicrobial Susceptibility Testing with the 24-Hour CLSI BMD Method for Testing Susceptibility of Candida Species to Fluconazole, Posaconazole, and Voriconazole by Use of Epidemiological Cutoff Values

“…MIC values were determined visually after 24 h of incubation as the lowest concentration of drug that caused a significant diminution (Ն50% inhibition) of growth below control levels (5,25,28).…”

“…We also provide an estimate of the CA between the two methods by using the ECVs previously determined for each antifungal agent and species of Candida (25,28). Finally, we have reanalyzed the 24-h fluconazole, posaconazole, and voriconazole MIC data from the earlier multicenter study of Espinel-Ingroff et al (10), using the CLSI ECVs to demonstrate further the comparability of the two methods.…”

“…In the interest of developing a sensitive measure to detect the emergence of resistance to both fluconazole and voriconazole, both the CLSI (25,28) and EUCAST (11,12) have defined the 24-h wild-type (WT) MIC distributions and epidemiological cutoff values (ECVs or ECOFFs) for the five most common species of Candida: C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, and C. krusei. ECVs (24 h) for posaconazole and Candida have been defined by the CLSI (28) but are not yet available for the EUCAST method.…”

“…In an effort to further pursue the harmonization of the CLSI and EUCAST BMD methods for testing the triazoles and Candida spp., we have utilized our 2009 ARTEMIS global antifungal surveillance database (8,28) to determine the EA between 24-h EUCAST and CLSI MICs for 1,056 clinical isolates of Candida species tested against fluconazole, posaconazole, and voriconazole. We also provide an estimate of the CA between the two methods by using the ECVs previously determined for each antifungal agent and species of Candida (25,28).…”

“…Each of these agents has good in vitro and clinical activity against most species of Candida (3,32). Despite the broad utilization of these agents in the prevention and treatment of invasive candidiasis (2,6,16,34), longitudinal surveillance studies have documented the sustained potency of all three triazoles since the introduction of fluconazole in 1990 (8,9,18,21,25,28,31). Although resistance to the triazoles remains relatively uncommon among cases of invasive candidiasis (IC) (19,23,25), numerous examples of clinical failure associated with elevated MICs to one or more of these agents have been reported (1,17,20,22,23,27).…”