title: In vitro antimicrobial activity of S-649266, a catechol-substituted siderophore cephalosporin, when tested against non-fermenting Gram-negative bacteria.
abstract: OBJECTIVE
  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.
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan akinobu.ito@shionogi.co.jp.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Ito
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kohira
authors.affiliation: International Health Management Associates, Inc., Schaumberg, IL 60173, USA.
authors.forename: Samuel K
authors.initials: SK
authors.lastname: Bouchillon
authors.affiliation: GlaxoSmithKline, Collegeville, PA 19426, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: West
authors.affiliation: GlaxoSmithKline, Collegeville, PA 19426, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rittenhouse
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Rhomberg
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Yoshizawa
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.
authors.forename: Rio
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamano
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D017262:Siderophores / Q000494:pharmacology*; D020615:Stenotrophomonas maltophilia / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D002396:Catechols; D002511:Cephalosporins; D017262:Siderophores