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Cefiderocol features an iron-binding catechol moiety that permits cell entry through iron-uptake systems and provides hydrolytic stability against β-lactamases to confer broad activity against aerobic Gram-negative bacteria, including Enterobacterales, Pseudomonas aeruginosa, Acinetobacter spp., Stenotroph
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
Understanding Cefiderocol Video
A scientifically based animation of how cefiderocol penetrates bacterial defenses, disrupts cell wall synthesis, and avoids resistance:
Antimicrobial Resistance Resources
Mechanisms of Carbapenem Resistance in Gram-negative Pathogens
Infographic describing the primary mechanisms by which carbapenem resistance occurs in Gram-negative pathogens
In Vitro Activity of Selected Antibiotics Against β-Lactam–Resistant Gram-Negative Pathogens
Infographic showing the in vitro activity of cefiderocol and β-lactam/β-lactamase inhibitor combinations across key β-lactam–resistant Gram-negative pathogens, stratified by resistance mechanisms
Abbreviations: MOA=mechanism of action; MOCE=mechanism of cell entry.
References:
- Ito A, et al. Antimicrob Agents Chemother. 2016;60(12):7396-7401.
- Aoki T, et al. Eur J Med Chem. 2018;155:847-868.
- Ito-Horiyama T, et al. Antimicrob Agents Chemother. 2016;60(7):4384-4386.
- Kohira N, et al. Antimicrob Agents Chemother. 2016;60(2):729-734.
- Ito A, et al. Antimicrob Agents Chemother. 2018;62(1):e01454-17.
- Kazmierczak KM, et al. Int J Antimicrob Agents. 2019;53(2):177-184.
- Iregui A, et al. Microb Drug Resist. 2020;26(7):722-726 and S1-S3.
- Fetroja® [package insert]. Florham Park, NJ: Shionogi Inc.