Shionogi’s cefiderocol (Fetroja) is an antibiotic that was initially approved by the FDA in November 2019 and was indicated for the treatment of complicated urinary tract infections in patients 18 years of age or older. The FDA then approved cefiderocol again in September 2020 for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.
Cefiderocol is a cephalosporin antibiotic with a novel mechanism for penetrating the outer cell membrane of Gram-negative pathogens by acting as a siderophore. In addition to entering cells by passive diffusion through porin channels, cefiderocol binds to ferric iron and is actively transported into bacterial cells through the outer membrane via the bacterial iron transporters, which function to incorporate this essential nutrient for bacteria. These mechanisms allow cefiderocol to achieve high concentrations in the periplasmic space where it can bind to penicillin-binding proteins and inhibit cell wall synthesis in the bacterial cells.1
The antimicrobial continues to be studied against different pathogens and the company presented data at the recent ID Week.
ID Week Presentations
Oral #513: Cefiderocol Retains in vitro Activity Against Enterobacterales Non-Susceptible to beta-lactam-beta-lactamase Inhibitor Combinations
Poster #1363: Cefiderocol Activity Against Clinical Enterobacterales Isolates Carrying Metallo-beta-lactamase Genes in United States and European Hospitals (2020–2023)
Poster #1364: Cefiderocol Activity Against Pseudomonas aeruginosa Clinical Isolates Carrying Metallo-beta-lactamase Genes in United States and European Hospitals (2020–2023)
Poster #1530: Evaluation of Phenotypic Cross-Resistance Between Cefiderocol and beta-lactam/beta-lactamase Inhibitor Combinations Against Pseudomonas aeruginosa Isolates from US Medical Centers
“I think one of the important things with cefiderocol is to understand that the molecule is itself different than other beta lactams. So they have a very stable structure, especially with the catechol group that given the mechanism of action is able to enter the cell using a different path than other beta lactams,” said Jose Alexander, MD, ABMM, ABAIM, FCCM, CIC, ASCP, BCMAS, medical director for the microbiology laboratory at Adventhealth in Orlando, FL.
Alexander points out the importance of having other treatment options such as cefiderocol for patients with challenging gram-negative infections and the rise of antimicrobial resistance.
“Being able to have access to an agent that can overcome resistant of metallo-beta-lactamases, makes them a significant tool in the lab, but also for clinician, especially when you find these metallo-beta-lactamases are increasing across the US.”
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