Cefiderocol Microbiology Resource Center

A centralized hub for information on cefiderocol susceptibility testing and surveillance

Cefiderocol Mechanism of Action

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Cefiderocol was rationally designed to feature a unique iron-binding catechol moiety that permits a novel mechanism of cell entry and hydrolytic stability against β-lactamases to confer broad activity against aerobic Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, Acinetobacter spp., Stenotrophomonas maltophilia, and isolates that are carbapenem- and multidrug-resistant.1-8

Cefiderocol MOA/MOCE Animation

Please refer to the Prescribing Information for full indications and safety information.

A simplified view of how cefiderocol utilizes bacterial iron transport channels to enter the cell and bypass carbapenem resistance mechanisms:

  • Via its catechol moiety, cefiderocol employs a “Trojan horse” strategy that capitalizes on the bacteria’s innate need for iron by mimicking a bacterial siderophore bound to free extracellular iron, enabling it to be actively transported into bacterial cells through iron transport channels; cefiderocol can also gain entry to bacterial cells through passive diffusion through porin channels1,3,5
  • Once inside the bacterial cell in the periplasmic space, cefiderocol dissociates from iron, and the cephalosporin core binds to penicillin-binding proteins and inhibits peptidoglycan cell wall synthesis, leading to cell death4,5
  • Based on its unique structure and novel mechanism of cell entry, cefiderocol remains active against Gram-negative bacteria that employ mechanisms that commonly confer resistance to carbapenems, including the production of β-lactamases, upregulation of efflux pumps, and loss or mutation of porin channels3-8
Cefiderocol MOA (2).pptx
Cefiderocol MOA (2).pptx (1)

Understanding Cefiderocol Video

A scientifically based animation of how cefiderocol penetrates bacterial defenses, disrupts cell wall synthesis, and avoids resistance:

Spectrum of Activity Table

Cefiderocol in vitro activity against select Gram-negative pathogens with prevalent resistance mechanisms:

In vitro* susceptibility data specific to resistant Gram-negative pathogens for antibiotics indicated for adult patients with cUTI and/or HABP/VABP since 2014

Enterobacterales P. aeruginosa A. baumannii S. maltophilia Other resistance mechanisms​
ESBLs and/or​ AmpC Serine​ carbapenemases​ Metallo-​β-lactamases​ Serine​ β-lactamases​ (including AmpC) Metallo-​β-lactamases​ Serine carbapenemases (OXA) and/or AmpC​ Intrinsic​ resistance due​ to L1 metallo-​β-lactamasea Porin channel​ mutations​ Efflux pump​ up-regulation​
Cefiderocol8
Ceftolozane/tazobactam10
Ceftazidime/avibactam11 + / –
Meropenem/vaborbactam12 + / – + / –
Plazomicin13 + / – + / –
Imipenem/cilastatin/​ relebactam14
Sulbactam/durlobactam15 b

This information should not be used to make efficacy or safety comparisons between or among mentioned products. Some products are also indicated for different pathogens and patient populations and may have additional indications.

✓ = Active; + / – = Limited Activity; Blank = Inactive, No Data​

*In vitro susceptibility does not necessarily correlate with clinical efficacy.​

aS. maltophilia produces an inducible L1 enzyme, a metallo-β-lactamase, conferring an intrinsic resistance to all carbapenems.16,17

bDoes not include AmpC.

cUTI=complicated urinary tract infection; ESBL=extended-spectrum β-lactamase; HABP=hospital-acquired bacterial pneumonia; OXA=oxacillinase; VABP=ventilator-associated bacterial pneumonia.

Abbreviations: cUTI=complicated urinary tract infection; ESBL=extended-spectrum β-lactamase; HABP=hospital-acquired bacterial pneumonia; MOA=mechanism of action; MOCE=mechanism of cell entry; OXA=oxacillinase; VABP=ventilator-associated bacterial pneumonia.

References:

  1. Ito A, et al. Antimicrob Agents Chemother. 2016;60(12):7396-7401.
  2. Aoki T, et al. Eur J Med Chem. 2018;155:847-868.
  3. Ito-Horiyama T, et al. Antimicrob Agents Chemother. 2016;60(7):4384-4386.
  4. Kohira N, et al. Antimicrob Agents Chemother. 2016;60(2):729-734.
  5. Ito A, et al. Antimicrob Agents Chemother. 2018;62(1):e01454-17.
  6. Kazmierczak KM, et al. Int J Antimicrob Agents. 2019;53(2):177-184.
  7. Iregui A, et al. Microb Drug Resist. 2020;26(7):722-726 and S1-S3.
  8. Fetroja® [package insert]. Florham Park, NJ: Shionogi Inc.
  9. Wise MG, et al. Microb Drug Resist. 2023;29(8):360-370.
  10. Zerbaxa® [package insert]. Rahway, NJ; Merck Sharp & Dohme LLC; 2022.
  11. Avycaz® [package insert]. North Chicago, IL; AbbVie, Inc.; 2025.
  12. Vabomere® [package insert]. Parsippany, NJ; Melinta Therapeutics, LLC; 2024.
  13. Zemdri® [package insert]. Warren, NJ; Cipla Therapeutics Inc.; 2023.
  14. RecarbrioTM [package insert]. Rahway, NJ; Merck Sharp & Dohme LLC; 2022.
  15. Xacduro® [package insert]. La Jolla Pharmaceutical Company; 2023.
  16. Ruppé É, Woerther P-L, Barbier F. Ann Intensive Care. 2015;5(1):1-15.
  17. Sánchez MB. Front Microbiol. 2015;6:1-7.