Abstract
ABSTRACTCefiderocol (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.
Highlights
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 an antibacterial spectrum that is significantly different from that of carbapenem antibiotics, which have been mainly used for the treatment of Gram-negative bacterial infections
The global surveillance studies of cefiderocol, SIDERO-WT-2014, using recent clinical isolates (n ϭ 9,205) against Enterobacteriaceae and nonfermenting bacteria such as P. aeruginosa, A. baumannii, and S. maltophilia, including MDR strains, and other studies to evaluate the antibacterial activity of cefiderocol against well-characterized carbapenem-resistant Gram-negative
Summary
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 (CFDC; S-649266), a novel catechol-substituted siderophore cephalosporin, is structurally different from other recently developed hydroxypyridone-substituted siderophore monobactam antibiotics such as BAL30072, MB-1, and MC-1 and has been reported to have potent antibacterial activity against MDR Gram-negative pathogens, including carbapenemresistant strains of Enterobacteriaceae, P. aeruginosa, and A. baumannii, as well as potent in vivo efficacy against multiple clinical strains of Gram-negative bacteria in mouse lung infection models This is the first report evaluating the in vitro features of cefiderocol, including its antibacterial spectrum against Gram-negative and Grampositive bacteria and its mode of action, such as penicillin-binding protein (PBP) binding affinity and morphological changes, as well as the impacts of various. -lactamases, efflux pump overexpression, and deficiency of porin or iron transporter on the in vitro activity
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