Cefiderocol Susceptibility Testing 

Cefiderocol is a novel siderophore cephalosporin antibiotic designed to treat infections caused by multidrug-resistant Gram-negative bacteria, including carbapenem-resistant organisms. Cefiderocol enters bacterial cells by utilizing the siderophore iron transport system, allowing it to overcome resistance mechanisms such as porin loss. It is active against organisms producing extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases, and even some metallo-beta-lactamases (MBLs). Susceptibility testing for cefiderocol is critical for ensuring appropriate use and monitoring emerging resistance.

Content:

• Testing Methods:
  • Broth Microdilution (BMD):
    • CLSI and EUCAST recommend broth microdilution as the gold standard for determining cefiderocol MICs.
    • Iron-depleted cation-adjusted Mueller-Hinton Broth (ID-CAMHB) must be used to simulate physiological conditions for optimal testing.
• • E-test (Gradient Diffusion):
    • Not recommended for cefiderocol due to inconsistent results and lack of standardization.
  • Automated Testing Systems:
    • Automated systems like Vitek or Phoenix may incorporate cefiderocol in their panels; however, validation and calibration for cefiderocol are still ongoing in many systems.

Application:

• Clinical Use:
  • Cefiderocol is approved for treating:
    • Complicated urinary tract infections (cUTIs).
    • Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP).
    • Bloodstream infections (BSIs) caused by multidrug-resistant Gram-negative bacteria.
    • Carbapenem-resistant infections due to Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacterales.
• Antimicrobial Stewardship:
  • Helps guide targeted therapy for multidrug-resistant infections, avoiding unnecessary use of last-line antibiotics.
• Epidemiological Surveillance:
  • Monitors the emergence of resistance among carbapenemase-producing organisms and other multidrug-resistant pathogens.

Cefiderocol susceptibility testing is essential for managing infections caused by multidrug-resistant Gram-negative pathogens, including carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa.