Cefiderocol: A Review in Serious Gram-Negative Bacterial Infections

Plain Language Summary Infections caused by carbapenem-resistant (CR) Enterobacterales and nonfermenters (such as Pseudomonas, Acinetobacter, Stenotrophomonas, Burkholderia) are a major global health threat. Cefiderocol, a cephalosporin with activity against CR Enterobacterales and nonfermenters, uses the bacteria's own iron uptake system to gain cell entry, like a Trojan horse. Once inside, the drug disrupts the formation of the bacterial cell wall, killing the bacteria. Cefiderocol is approved for the treatment of serious Gram-negative bacterial infections. In clinical trials, cefiderocol was effective versus carbapenems or best available therapy for complicated urinary tract infections, nosocomial pneumonia and bloodstream infections/sepsis, including those caused by CR bacteria. The drug had a good tolerability and safety profile. Thus, cefiderocol is a useful addition to the current treatment options for adults with cefiderocol-susceptible Gram-negative bacterial infections for whom there are limited treatment options. Intravenous cefiderocol (Fetroja(R); Fetcroja(R)) is the first siderophore cephalosporin approved for the treatment of adults with serious Gram-negative bacterial infections. Cefiderocol is stable against all four Ambler classes of beta-lactamases (including metallo-beta-lactamases) and exhibits excellent in vitro activity against many clinically relevant Gram-negative pathogens, including multidrug resistant strains. In randomized, double-blind clinical trials, cefiderocol was noninferior to imipenem/cilastatin for the treatment of complicated urinary tract infections (cUTI) and to meropenem for nosocomial pneumonia. Furthermore, in a pathogen-focused clinical trial in patients with carbapenem-resistant (CR) infections, cefiderocol showed comparable efficacy to best available therapy (BAT), albeit all-cause mortality rate was higher in the cefiderocol arm, the cause of which has not been established. Cefiderocol had a good tolerability and safety profile in clinical trials. Thus cefiderocol is a novel, emerging, useful addition to the current treatment options for adults with susceptible Gram-negative bacterial infections (including cUTI and nosocomial pneumonia) for whom there are limited treatment options.

Automated summary

Cefiderocol is a cephalosporin with activity against carbapenem-resistant bacteria and nonfermenters, using the bacteria's iron uptake system to disrupt the cell wall and kill the bacteria. It has shown good effectiveness and safety in clinical trials for various serious bacterial infections, providing a useful addition to treatment options for adults with limited choices.