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.