<i>In Vitro</i> Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria

Abstract

Cefiderocol (CFDC; S-649266), a novel parenteral siderophore cephalosporin conjugated with a catechol moiety, has a characteristic antibacterial spectrum with a potent activity against a broad range of aerobic Gram-negative bacterial species, including carbapenem-resistant strains of <i>Enterobacteriaceae</i> and nonfermenting bacteria such as <i>Pseudomonas aeruginosa</i> and <i>Acinetobacter baumannii</i> Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP3) of <i>Enterobacteriaceae</i> and nonfermenting bacteria similar to that of ceftazidime. A deficiency of the iron transporter PiuA in <i>P. aeruginosa</i> or both CirA and Fiu in <i>Escherichia coli</i> caused 16-fold increases in cefiderocol MICs, suggesting that these iron transporters contribute to the permeation of cefiderocol across the outer membrane. The deficiency of OmpK35/36 in <i>Klebsiella pneumoniae</i> and the overproduction of efflux pump MexA-MexB-OprM in <i>P. aeruginosa</i> showed no significant impact on the activity of cefiderocol.