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

Author information

Affiliations

  • 1. Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan
      Authors
    • Ito A 1
    (1 author)
  • 2. Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.
      Authors
    • Kohira N 2
    • Yoshizawa H 2
    • Nakamura R 2
    • Tsuji M 2
    • Yamano Y 2
    (5 authors)
  • 3. International Health Management Associates, Inc., Schaumberg, IL 60173, USA.
      Authors
    • Bouchillon SK 3
    (1 author)
  • 4. GlaxoSmithKline, Collegeville, PA 19426, USA.
      Authors
    • West J 4
    • Rittenhouse S 4
    (2 authors)
  • 5. JMI Laboratories, North Liberty, IA 52317, USA.
      Authors
    • Sader HS 5
    • Rhomberg PR 5
    • Jones RN 5
    (3 authors)

ORCIDs linked to this article

The Journal of Antimicrobial Chemotherapy, 07 Dec 2015, 71(3):670-677
https://doi.org/10.1093/jac/dkv402 PMID: 26645269 

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.

Full text links 

Read article at publisher's site: https://doi.org/10.1093/jac/dkv402

Read article for free, from open access legal sources, via Unpaywall: https://academic.oup.com/jac/article-pdf/71/3/670/6993403/dkv402.pdfUnpaywall

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