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

被引:289
作者
Ito, Akinobu [1 ]
Sato, Takafumi [1 ]
Ota, Merime [1 ]
Takemura, Miki [1 ]
Nishikawa, Toru [1 ]
Toba, Shinsuke [1 ]
Kohira, Naoki [1 ]
Miyagawa, Satoshi [1 ]
Ishibashi, Naoki [1 ]
Matsumoto, Shuhei [1 ]
Nakamura, Rio [1 ]
Tsuji, Masakatsu [1 ]
Yamano, Yoshinori [1 ]
机构
[1] Shionogi & Co Ltd, Toyonaka, Osaka, Japan
关键词
cefiderocol; time kill; penicillin-binding protein; PBP; morphology; iron transporter; efflux pump; porin; PENICILLIN-BINDING PROTEINS; ESCHERICHIA-COLI K-12; PSEUDOMONAS-AERUGINOSA; ANTIMICROBIAL ACTIVITY; CONJUGATED MONOCARBAM; RESISTANCE; S-649266; AGENTS; EFFICACY; CATECHOL;
D O I
10.1128/AAC.01454-17
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:11
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