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

Background: Cefiderocol (FDC) presents challenges in antimicrobial susceptibility testing (AST). The reference standard is the broth microdilution (BMD) method with iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB). Still, it is cumbersome for routine clinical laboratory use, while variable accuracy has been reported with available commercial systems. Variability in interpretive criteria and areas of technical uncertainty (ATUs) further complicate assessments. Methods: This review and expert opinion presents: (1) an overview of non-susceptibility to FDC and then delves into the performance of current FDC AST methods for Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii complex; (2) a practical decision framework to guide clinical microbiologists in making informed choices. Results and Conclusions: For Enterobacterales, including carbapenem-resistant Enterobacterales (CRE), and Pseudomonas aeruginosa, we propose disk diffusion (DD) as a preliminary screening tool to classify isolates as susceptible (S) or resistant (R). Confirmatory 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 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 < 17 mm are considered non-susceptible and should be confirmed with standard BMD. Those between 17 and 22 mm require retesting with a commercial BMD method, with further confirmation recommended if S isolates with zones ≥ 23 mm may be considered S without additional testing.