Cefiderocol Antimicrobial Susceptibility Testing against Multidrug-Resistant Gram-negative Bacilli: A Comparison of Disk Diffusion to Broth Microdilution.

Background: Cefiderocol antimicrobial susceptibility testing (AST) poses challenges because of its unique mechanism of action (i.e., requiring an iron depleted state) and due to differences in interpretative criteria by the Clinical and Laboratory Standards Institute (CLSI), U.S. Food and Drug Administration (FDA), and European Committee of Antimicrobial Susceptibility Testing (EUCAST). Our objective was to compare cefiderocol disk diffusion methods (DD) to broth microdilution (BMD) for AST of Gram-negative bacilli (GNB). Methods: Cefiderocol AST was performed on consecutive carbapenem-resistant Enterobacterales (CRE; 58) and glucose-non-fermenting GNB (50) isolates by BMD (lyophilized panels; Sensititer, Thermo Fisher) and DD (30 μg; Research Use Only [RUO] MASTDISCS and FDA-cleared HardyDisks). Results were interpreted using investigational CLSI, FDA, and EUCAST breakpoints (BPs). Categorical agreement (CA), minor errors (mE), major errors (ME), and very major errors (VME) were calculated for DD methods. Results: The susceptibility of all isolates by BMD ranged from 72% (FDA), 75% (EUCAST) and 90% (CLSI). For DD methods, EUCAST BPs demonstrated lower susceptibility at 65% and 66%, compared to 74% and 72% (FDA), and 87% and 89% (CLSI) by HardyDisks and MASTDISCS, respectively. CA ranged from 75% to 90%, with 8-25% mE, 0-19% ME, and 0-20% VME and varied based on disk, GNB, and BPs evaluated. Both DD methods performed poorly for Acinetobacter baumannii complex. Conclusions: There is considerable variability when interpreting cefiderocol ASTs using CLSI, FDA, and EUCAST breakpoints. DD offers a convenient, alternative approach to BMD methods for cefiderocol AST testing, with the exception of A. baumannii complex isolates.