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.
Copyright © 2017 Ito et al.
MeSH terms
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Acinetobacter baumannii / drug effects*
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Anti-Bacterial Agents / pharmacology*
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Bacterial Outer Membrane Proteins / biosynthesis
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Bacterial Proteins / genetics
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Carbapenem-Resistant Enterobacteriaceae / drug effects*
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Cefiderocol
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Cephalosporins / metabolism
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Cephalosporins / pharmacology*
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Drug Resistance, Multiple, Bacterial
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Escherichia coli / drug effects*
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Escherichia coli / genetics
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Escherichia coli Proteins / genetics
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Klebsiella pneumoniae / drug effects*
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Klebsiella pneumoniae / genetics
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Membrane Transport Proteins / biosynthesis
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Microbial Sensitivity Tests
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Penicillin-Binding Proteins / metabolism
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Porins / genetics
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Pseudomonas aeruginosa / drug effects*
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Pseudomonas aeruginosa / genetics
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Receptors, Cell Surface / genetics
Substances
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Anti-Bacterial Agents
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Bacterial Outer Membrane Proteins
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Bacterial Proteins
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Cephalosporins
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Escherichia coli Proteins
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Membrane Transport Proteins
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MexA protein, Pseudomonas aeruginosa
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MexB protein, Pseudomonas aeruginosa
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OmpK35 porin, Klebsiella pneumoniae
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OmpK36 protein, Klebsiella pneumoniae
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OprM protein, Pseudomonas aeruginosa
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Penicillin-Binding Proteins
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Porins
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Receptors, Cell Surface
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colicin receptor, E coli