Evaluation of Japan-specific cefiderocol susceptibility testing methods in multidrug-resistant gram-negative isolates...

Cefiderocol (CFDC) exhibits potent in vitro activity against multidrug-resistant Gram-negative bacilli (MDR-GNB), yet standardized susceptibility testing remains technically demanding. This study evaluated the reproducibility and categorical agreement (CA) of broth microdilution (BMD), MIC dry plate (DP), and disk diffusion (DD) using MDR-GNB from Japan and Bangladesh. To our knowledge, this is the first systematic assessment of Japan-specific commercial platforms for CFDC testing.

A total of 452 MDR-GNB isolates, including 272 Enterobacterales and 180 non-fermenters (Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia), were tested using BMD and two commercial platforms. Reproducibility was assessed in triplicate, and essential agreement, CA, and error rates were determined with BMD as the reference.

BMD demonstrated >90 % reproducibility across species. DP and DD showed reduced reproducibility and agreement for NDM-producing Enterobacterales, with CA of 54 % for DP and 63 % for DD. Most discrepancies were minor errors. Trailing effects and visual artifacts contributed to elevated MICs, particularly in DP.

The performance of simplified CFDC susceptibility methods varies by species and resistance mechanism, with notable limitations for NDM producers. While DP and DD remain practical tools for routine laboratories, their use requires caution. Parallel DP-DD testing does not replace BMD but can help identify discrepant results requiring confirmation, particularly for NDM-producing isolates.