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

• Published in: Journal of antimicrobial chemotherapy 2016-03, Vol.71 (3), p.670-677
• Main Authors: Ito, Akinobu, Kohira, Naoki, Bouchillon, Samuel K, West, Joshua, Rittenhouse, Stephen, Sader, Helio S, Rhomberg, Paul R, Jones, Ronald N, Yoshizawa, Hidenori, Nakamura, Rio, Tsuji, Masakatsu, Yamano, Yoshinori
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Anti-Bacterial Agents - pharmacology; Antibiotics; Antimicrobial agents; Bacteria; Catechols - pharmacology; Cephalosporins - pharmacology; Drug resistance; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Siderophores - pharmacology; Stenotrophomonas maltophilia; Stenotrophomonas maltophilia - drug effects
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkv402

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. MIC values of S-649266 were determined in Mueller-Hinton broth or Iso-Sensitest broth supplemented with apo-transferrin. 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. S-649266 is a novel antibiotic with potent in vitro activity against a range of non-fermenting Gram-negative bacteria, including MDR strains.