In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria.

Article Details

Citation

Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y

In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria.

Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan.

PubMed ID
29061741 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
CefiderocolD-alanyl-D-alanine carboxypeptidase DacBProteinEscherichia coli (strain K12)
Yes
Inhibitor
Details
CefiderocolPenicillin-binding protein 1AProteinPseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Yes
Inhibitor
Details
CefiderocolPenicillin-binding protein 1BProteinPseudomonas aeruginosa
Yes
Inhibitor
Details
CefiderocolPenicillin-binding protein 2ProteinPseudomonas aeruginosa
Yes
Inhibitor
Details
CefiderocolPenicillin-binding protein 3ProteinPseudomonas aeruginosa
Yes
Inhibitor
Details
Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
CefiderocolCatecholate siderophore receptor FiuProteinEscherichia coli (strain K12)
No
Substrate
Details
CefiderocolColicin I receptorProteinEscherichia coli (strain K12)
No
Substrate
Details
CefiderocolMexAB-OprM efflux system (Protein Group)Protein groupPseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
No
Substrate
Details
CefiderocolPutative outer membrane ferric siderophore receptorProteinPseudomonas aeruginosa (strain UCBPP-PA14)
No
Substrate
Details