Harmonizing antimicrobial susceptibility testing: a comparison of CLSI and EUCAST categorizations

Antimicrobial susceptibility testing remains a cornerstone of clinical microbiology and antimicrobial stewardship. Yet, two major interpretative frameworks coexist internationally: the Clinical and Laboratory Standards Institute (CLSI),1 widely used in North America and Asia, and the European Committee on Antimicrobial Susceptibility Testing (EUCAST),2 which is now the standard across Europe and is increasingly being adopted worldwide. While both systems aim to ensure that laboratory data guide rational antimicrobial use, their conceptual and operational divergences have practical implications for clinicians, laboratories and surveillance programmes. The purpose of this commentary is to reflect on how differing frameworks—each with distinct strengths and limitations—shape clinical practice, laboratory workflows and antimicrobial resistance (AMR) surveillance. The CLSI approach maintains the long-standing tripartite classification into Susceptible (S), Intermediate (I), and Resistant (R). The Intermediate category historically served a dual role: a technical buffer zone accommodating test variability and a clinical category reflecting uncertain therapeutic success. In 2019, EUCAST redefined this framework by reassigning the meaning of Susceptible, increased exposure (SIE).3 This evolution exemplifies EUCAST’s effort to align susceptibility categorization more closely with pharmacokinetic and pharmacodynamic (PK and PD) principles, but it also illustrates how conceptual innovation can generate implementation challenges when translated into routine practice. The redefinition emphasized PK and PD principles, promoting the view that many ‘borderline’ isolates may still respond to therapy, provided that dosing or administration routes are optimized. However, early implementation of this new interpretation was not without pitfalls. In particular, for Pseudomonas aeruginosa, the SIE category was initially misinterpreted in some centres, leading to an overuse of broad-spectrum β-lactams—especially meropenem—when narrower spectrum could have been appropriate (Table 1).4,5 This illustrates how conceptual refinements, though scientifically sound, can generate clinical confusion when not accompanied by clear communication and stewardship guidance. This conceptual shift had an unintended methodological consequence: by transforming ‘I’ into a fully interpretable clinical category, EUCAST effectively lost the technical buffer that had previously absorbed analytical uncertainty.