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The development of resistance to cefiderocol in the clinical setting appears to be rare, and no single mechanism of resistance has consistently been associated with reduced cefiderocol susceptibility.1-23 Should you encounter an isolate that appears to be non-susceptible to cefiderocol, Shionogi offers a program that will test the isolate free of charge to determine the resistance profile for research purposes.

Review Article on Cefiderocol Resistance

Cefiderocol: Systematic Review of Mechanisms of Resistance, Heteroresistance and In Vivo Emergence of Resistance

Karakonstantis S, Rousaki M, Kritsotakis EI. Antibiotics (Basel). 2022;11(6):723.

Key Points

  • This systematic review identifies several potential cefiderocol resistance mechanisms that must often act in combination to overcome cefiderocol’s effectiveness
  • A predominant mechanism of resistance appears to involve co-expression of multiple β-lactamases in combination with permeability defects associated with mutations affecting porins or siderophore receptors
  • While heteroresistance has been observed—especially in A. baumannii—its clinical significance is uncertain due to low observed resistance in patients

Cefiderocol Resistant Isolate Testing Program

A free laboratory resource provided by Shionogi to characterize isolates potentially resistant to cefiderocol for research purposes 

How the resistant isolate program works
  • Send the isolate(s) to IHMA via FedEx using the shipping kit provided to your lab
  • IHMA will repeat identification and susceptibility testing using MALDI-TOF/BMD with ID-CAMHB
If MICs are elevated:

(Antimicrobial susceptibility testing may take 1-2 weeks)

Enterobacterales Pseudomonas aeruginosa Acinetobacter baumannii complex

Stenotrophomonas maltophilia and other pathogens

Then evaluation of:

(Whole genome sequencing of resistant isolates may take 1-2 months)

β-lactamases

Penicillin-binding protein alterations

Porin channel alterations

Changes in iron transport genes

Testing is provided at no cost to your institution.

This program is intended for research and investigation purposes only, not for patient care.

IHMA sends results to Shionogi, which will then be shared with your site through our Medical Affairs team.

Shionogi is committed to antimicrobial stewardship, contributing to knowledge of antimicrobial resistance and improving the understanding of potential cefiderocol resistance.

Have questions regarding the Resistant Isolate Program?

Our team is here to help. Please contact us at (800) 849-9707, [email protected], or Shionogi Medical.

Abbreviations: BMD=broth microdilution; ID-CAMHB=iron-depleted cation-adjusted Mueller Hinton Broth; IHMA=International Health Management Associates; MALDI-TOF=matrix-assisted laser desorption/ionization-time of flight; MIC=minimum inhibitory concentration.

References:

  1. Shortridge D, et al. Microbiol Spectr. 2022;10(2):e0271221.
  2. Wise MG, et al. Microb Drug Resist. 2023;29(8):360-370.
  3. Karakonstantis S, et al. Clin Microbiol Infect. 2024;30(2):178-188.
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  16. Shields RK, et al. Clin Infect Dis. 2020;71(10):2713-2716.
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  19. Simner PJ, et al. Open Forum Infect Dis. 2021;8(7):ofab311.
  20. Ito A, et al. Antimicrob Agents Chemother. 2018;62(1):e01454-17.
  21. Malik S, et al. Antimicrob Agents Chemother. 2020;64(11):e01221-20.
  22. Streling AP, et al. Clin Infect Dis. 2021;73(11):e4472-e4474.
  23. Polani R, et al. Emerg Infect Dis. 2025;31(1):123-124.