PHOTO
[Photo credit: businesswire.com]
KEY POINTS
- Cefiderocol (Fetroja, formerly S-649266) is a siderophore cephalosporin and beta-lactam antibiotic that inhibits bacterial cell wall synthesis through binding to penicillin binding protein 3
- Cefiderocol is able to chelate ferric ions and use bacterial iron transport systems, which has been called a “Trojan Horse” strategy and translates to higher concentrations in the periplasmic space of susceptible Gram negatives
- Structural similarities to ceftazidime (C7-residue) and cefepime (C3-residue)
- FDA approved November 14, 2019 for the treatment of complicated urinary tract infections in patients 18 years or older
- Has a label warning for higher all-cause mortality versus other antibiotics in critically ill patients with multidrug-resistant Gram-negative bacterial infections
- The cause of the higher mortality is not established
- It was observed in patients treated for nosocomial pneumonia (i.e, HAP/VAP), bloodstream infections, and sepsis
- Has activity against a variety of drug-resistant Gram negative organisms, including some carbapenem-resistant bacteria
- Can have activity versus bacteria producing Ambler class A, B, C, or D beta-lactamases
- Includes NDM (Ambler class B)
- Can have activity versus some organisms harboring OmpK35/36 or OprD porin deletions
- Has activity versus Acinetobacter baumannii, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia
- Is active against some E. coli isolates containing the mcr-1
- Cross-resistance with other antimicrobials is yet to be identified
- Has no clinically relevant in vitro activity against most Gram-positive bacteria and anaerobic bacteria
- Can have activity versus bacteria producing Ambler class A, B, C, or D beta-lactamases
- Intravenous only dosed as 2gm IV every 8 hours administered over 3 hours
- Dose adjust for renal function, including creatinine clearance below 60 mL/min or above 120 mL/min
- Comes in 1gm vials
- Potential side effects include constipation, cough, diarrhea, headache, hypokalemia, increase AST/ALT, infusion site reactions, nausea or vomiting, rash, yeast infection
- Seizures and other CNS effects have occurred
- Not recommended for people with a known history of severe hypersensitivity to beta-lactams
- Manufactured by Shionogi & Co., Ltd
RESOURCES
- Cefiderocol (Fetroja) Package Insert
- FDA Cefiderocol Approval Notice
- Cefiderocol Susceptibility Information
- Cefiderocol: a promising antibiotic against multidrug-resistant Gram-negative bacteria (2019)
- Compassionate Use of Cefiderocol as Adjunctive Treatment of Native Aortic Valve Endocarditis Due to Extremely Drug-resistant Pseudomonas aeruginosa (2019)
- Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial (2019)
- Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli (2019)
- Cefiderocol: a novel siderophore cephalosporin (2018)
