The role of epidemiological cutoff values (ECVs/ECOFFs) in antifungal susceptibility testing and interpretation for uncommon yeasts and moulds.

The role of antimicrobial susceptibility testing is to aid in selecting the best agent for the treatment of bacterial and fungal diseases. This has been best achieved by the setting of breakpoints by Clinical Laboratory Standards Institute (CLSI) for prevalent Candida spp. versus anidulafungin, caspofungin, micafungin, fluconazole, and voriconazole. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) also has set breakpoints for prevalent and common Candida and Aspergillus species versus amphotericin B, itraconazole, and posaconazole. Recently, another interpretive category, the epidemiological cut off value, could aid in the early identification of strains with acquired resistance mechanisms. CLSI has postulated that epidemiological cut off values may, with due caution, aid physicians in managing mycosis by species where breakpoints are not available. This review provides (1) the criteria and statistical approach to establishing and estimating epidemiological cut off values (ECVs), (2) the role of the epidemiological cut off value in establishing breakpoints, (3) the potential role of epidemiological cut off values in clinical practice, (4) and the wide range of CLSI-based epidemiological cut off values reported in the literature as well as EUCAST and Sensititre Yeast One-ECVs. Additionally, we provide MIC/MEC (minimal inhibitory concentrations/minimum effective concentrations) ranges/modes of each pooled distribution used for epidemiological cut off value calculation. We focus on the epidemiological cut off value, the new interpretive endpoint that will identify the non-wild type strains (defined as potentially harboring resistance mechanisms). However, we emphasize that epidemiological cut off values will not categorize a fungal isolate as susceptible or resistant as breakpoints do, because the former do not account for the pharmacology of the antifungal agent or the findings from clinical outcome studies.