In vitro antibacterial properties of cefiderocol, a novel siderophore cephalosporin, against Gram-negative bacteria [PublishAheadOfPrint]

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 non-fermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP 3) of Enterobacteriaceae and non-fermenting bacteria similar to ceftazidime. Deficiency of iron-transporter of 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 outer membrane. Deficiency of OmpK35/36 in Klebsiella pneumoniae and overproduction of efflux pump MexA-MexB-OprM in P. aeruginosa showed no significant impact on the activity of cefiderocol.

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