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

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2018年 / 62卷 / 01期

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.

引用

页数：11

共 33 条

[21] Siderophores as drug delivery agents: application of the "Trojan Horse" strategy [J].