In Vitro 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 Enterobacteriaceae and nonfermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP3) of Enterobacteriaceae and nonfermenting bacteria similar to that of ceftazidime. A deficiency of the iron transporter PiuA in P. aeruginosa or both CirA and Fiu in Escherichia coli 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 Klebsiella pneumoniae and the overproduction of efflux pump MexA-MexB-OprM in P. aeruginosa showed no significant impact on the activity of cefiderocol.

Keywords: PBP; cefiderocol; efflux pump; iron transporter; morphology; penicillin-binding protein; porin; time kill.

FIG 1

Bactericidal activities of cefiderocol (a and c) and ceftazidime (b and d) against E. coli NIHJ JC-2 (a and b) and K. pneumoniae SR22291 (c and d). ID-CAMHB and CAMHB were used for cefiderocol and ceftazidime, respectively, as the test media.

FIG 2

Bactericidal activities of cefiderocol (a and c) and ceftazidime (b and d) against P. aeruginosa ATCC 27853 (a and b) and A. baumannii ATCC 17978 (c and d). ID-CAMHB and CAMHB were used for cefiderocol and ceftazidime, respectively, as the test media.