The in vitro susceptibilities of 1,099 molecularly identified clinical Candida isolates against 8 antifungal drugs were determined using the EUCAST microdilution method. A new simple, objective, and mathematically solid method for determining epidemiological cutoff values (ECOFFs) was developed by derivatizing the MIC distribution and determining the derivatized ECOFF (dECOFF) as the highest MIC with the maximum second derivative. The dECOFFs were similar (95% agreement within 1 dilution) to the EUCAST ECOFFs. Overall, low non-wild-type/resistance rates were found. The highest rates were found for azoles with C. parapsilosis (2.7 to 9.8%), C. albicans (7%), and C. glabrata (1.7 to 2.3%) and for echinocandins with C. krusei (3.3%), C. albicans (1%), and C. tropicalis (1.7%).KEYWORDS Candida, EUCAST, antifungal susceptibility testing, epidemiological cutoff value A lthough epidemiological cutoff values (ECOFFs) are not clinical breakpoints, they are useful and necessary for defining wild-type populations and detecting strains with MIC values outside the wild-type distribution that may reflect strains with reduced susceptibility (1, 2). However, for some antifungal drugs and Candida species, no ECOFFs hinder the detection of non-wild-type isolates. Determination of an ECOFF may be quite challenging, since it requires complex statistical analysis (3), and so far, no clear consensus on the best method has been reached. The CLSI is using a statistical approach whereby the log-normal distribution is iteratively fitted to different MIC subsets until the best fit is found (2). However, a perfect fit may not be attained, particularly for small MIC data sets or for nonsymmetric distributions or distributions with heavy tails. Truncated data cannot by analyzed because the normal distribution cannot be easily defined (3). Furthermore, the percentage of isolates that should be encompassed within the wild-type distribution is arbitrarily chosen to be between 95 and 99%, and it is strongly affected by the percentage of resistant isolates. Finally, different MIC subpopulations cannot be easily identified. For multimodal MIC distributions, a statistical approach was used to describe the MIC subpopulations of Aspergillus fumigatus and azoles (4). EUCAST utilized both a nonstatistical approach, namely, the "eyeball method," whereby ECOFFs are determined by visual inspection of the MIC distribution as the MIC at the beginning of the left tail, as well as the statistical approach mentioned above. Although with visual inspection one does not assume a specific shape of MIC distribution, it is subjective and difficult for nonsymmetrical distributions and MIC distributions with a high kurtosis.