How to: ECOFFs—the why,the how,and the don'ts of EUCAST epidemiological cutoff values

BackgroundIdentifying the MIC wild-type distribution and its delineation of species targeted for receiving antimicrobial agent breakpoints is an important first step for determining clinical breakpoints. Having the main responsibility in the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for characterizing the wild-type distributions and setting epidemiological cut-off values (ECOFFs), we explain the why, the how, and frequent misconceptions of wild-type MIC distributions and ECOFFs.ObjectivesTo clarify how wild-type MIC distributions and ECOFFs for agents and important target organisms are defined and determined and why these are important tools in microbiology, as well as to point to common misunderstandings and inappropriate use.SourcesThe EUCAST database of >40 000 MIC distributions; publications addressing the definition of wild-type MIC distributions, and ECOFFs in bacteria and fungi; and the EUCAST Standard Operating Procedure 10 Documents published by the European Centre for Disease Control and the European Food Safety Agency.ContentThe rationale for defining wild-type distributions and ECOFFs is explained. Setting breakpoints that bisect wild-type MIC distributions leads to poor methodological reproducibility and poor correlation between clinical outcome and susceptibility testing results. The methods applied by EUCAST to select distributions for aggregation and website display are described, highlighting the importance of incorporating data from multiple sources and methods. The methods used by EUCAST to estimate ECOFFs are outlined. Finally, the common misunderstandings of these processes are addressed.ImplicationsThe international community needs to agree on the phenotypic definitions of wild-type distributions. Systematic methods for developing and applying ECOFFs are essential to the conduct of phenotypic antimicrobial susceptibility testing and interpretation, which will remain the dominant laboratory method for the foreseeable future.