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J Antimicrob Chemother. 2016 Mar;71(3):670-7. doi: 10.1093/jac/dkv402. Epub 2015 Dec 7.

In vitro antimicrobial activity of S-649266, a catechol-substituted siderophore cephalosporin, when tested against non-fermenting Gram-negative bacteria.

Author information

1
Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan akinobu.ito@shionogi.co.jp.
2
Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.
3
International Health Management Associates, Inc., Schaumberg, IL 60173, USA.
4
GlaxoSmithKline, Collegeville, PA 19426, USA.
5
JMI Laboratories, North Liberty, IA 52317, USA.

Abstract

OBJECTIVES:

S-649266 is a parenteral siderophore cephalosporin antibiotic with a catechol moiety on its side chain. The in vitro antimicrobial activity of S-649266 against non-fermenting Gram-negative bacteria was evaluated and compared with the activities of meropenem, levofloxacin, cefepime, ceftazidime and piperacillin/tazobactam.

METHODS:

MIC values of S-649266 were determined in Mueller-Hinton broth or Iso-Sensitest broth supplemented with apo-transferrin.

RESULTS:

S-649266 showed potent in vitro activity against the non-fermenting Gram-negative bacteria Acinetobacter baumannii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia, including MDR strains such as carbapenem-resistant A. baumannii and metallo-β-lactamase-producing P. aeruginosa. MIC90s of S-649266 for A. baumannii, P. aeruginosa and S. maltophilia were 2, 1 and 0.5 mg/L, respectively, whereas MIC90s of meropenem were >16 mg/L. S-649266 showed potent in vitro activities against A. baumannii producing carbapenemases such as OXA-type β-lactamases, and P. aeruginosa producing metallo-β-lactamases such as IMP type and VIM type. MIC90 values for these A. baumannii strains and P. aeruginosa strains were 8 and 4 mg/L, respectively.

CONCLUSIONS:

S-649266 is a novel antibiotic with potent in vitro activity against a range of non-fermenting Gram-negative bacteria, including MDR strains.

PMID:
26645269
DOI:
10.1093/jac/dkv402
[Indexed for MEDLINE]

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