Cefiderocol: EUCAST criteria for disc diffusion and broth microdilution for antimicrobial susceptibility testing

Area of Science:

• Microbiology
• Clinical Diagnostics
• Antimicrobial Resistance

Background:

• Accurate determination of cefiderocol Minimum Inhibitory Concentrations (MICs) is crucial for guiding treatment against challenging bacterial infections.
• The reproducibility of cefiderocol MIC determination using broth microdilution (BMD) in iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) needed investigation.
• Development and validation of an alternative susceptibility testing method are essential for broader clinical application.

Purpose of the Study:

• To investigate the reproducibility of cefiderocol MIC determination using BMD.
• To develop and validate the EUCAST disc diffusion (DD) method for cefiderocol susceptibility testing.
• To establish cefiderocol breakpoints for key bacterial pathogens using both BMD and DD methods.

Main Methods:

• Cefiderocol MICs were determined for wild-type (WT) and non-WT isolates using BMD with ID-CAMHB according to EUCAST guidelines.
• The EUCAST DD method was performed using cefiderocol 30 μg discs on Mueller-Hinton agar.
• MICs were correlated with zone diameters (ZD), and zone diameter breakpoints (BP) were determined; external laboratory validation was conducted.

Main Results:

• MIC and ZD distributions for cefiderocol against WT isolates were established.
• Cefiderocol ZD breakpoints were set: susceptible ≥22 mm, resistant <22 mm for Enterobacterales and Pseudomonas aeruginosa.
• The DD method demonstrated robustness with no problematic variation between discs, media, or laboratories, and achieved target zone diameters for control strains.

Conclusions:

• The EUCAST disc diffusion (DD) method is a robust and user-friendly approach for cefiderocol susceptibility testing.
• The developed DD method provides reliable results for guiding cefiderocol therapy.
• For isolates with results falling within areas of technical uncertainty (ATU), confirmatory MIC testing is recommended.