Evaluating Antimicrobial Susceptibility Testing Methods for Cefiderocol: A Review and Expert Opinion on Current Practices and Future Directions

Cefiderocol (FDC) presents challenges in antimicrobial susceptibility testing (AST). The broth microdilution (BMD) method with iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB), is the reference standard but cumbersome for routine clinical la-boratory use, while variable accuracy has been reported with available commercial systems. Variability in interpretive criteria and areas of technical uncertainty (ATUs) further complicate assessments. This review and expert opinion firstly presents an overview on non-susceptibility to FDC and then deeps into the performance of current FDC AST methods for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter bau-mannii complex, proposing decision frameworks to guide clinical microbiologists in making informed choices. For Enterobacterales, including carbapenem-resistant Enter-obacterales (CRE), and Pseudomonas aeruginosa, we propose disk diffusion (DD) as a preliminary screening tool to classify isolates as susceptible (S) or resistant (R). Con-firmatory testing using the UMIC® FDC system or the ID-CAMHB BMD method is recommended for R isolates. In cases of discrepancy, repeating the test with ID-CAMHB BMD is advised. Additionally, isolates falling within the ATU during DD testing should be retested using either the UMIC® system or ID-CAMHB BMD. For A. baumannii complex, since EUCAST breakpoints have not been defined yet,, we propose a stepwise framework based on the first DD result; isolates with inhibition zones.