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, , and 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 , 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 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.