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

<jats:title>ABSTRACT</jats:title> <jats:p> 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 <jats:named-content content-type="genus-species">Enterobacteriaceae</jats:named-content> and nonfermenting bacteria such as <jats:named-content content-type="genus-species">Pseudomonas aeruginosa</jats:named-content> and <jats:named-content content-type="genus-species">Acinetobacter baumannii</jats:named-content> . Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP3) of <jats:named-content content-type="genus-species">Enterobacteriaceae</jats:named-content> and nonfermenting bacteria similar to that of ceftazidime. A deficiency of the iron transporter PiuA in <jats:named-content content-type="genus-species">P. aeruginosa</jats:named-content> or both CirA and Fiu in <jats:named-content content-type="genus-species">Escherichia coli</jats:named-content> 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 <jats:named-content content-type="genus-species">Klebsiella pneumoniae</jats:named-content> and the overproduction of efflux pump MexA-MexB-OprM in <jats:named-content content-type="genus-species">P. aeruginosa</jats:named-content> showed no significant impact on the activity of cefiderocol. </jats:p>