252S-649266, a Novel Siderophore Cephalosporin: In vitro activity against Gram-negative bacteria

Background. S-649266 (’266) is a novel catechol-substituted siderophore cephalosporin for injection discovered by Shionogi and Co., Ltd. In this study, in vitro antibacterial activity of ’266 is evaluated against the clinical isolates of Gram-negative bacteria. Methods. MIC was measured by broth microdilution method according to Clinical and Laboratory Standard Institute except that CAMHB supplemented with 20 μM of apo-transferrin (apo-T) was used for evaluation of the activity of ’266. In the case of Acinetobacter baumannii, Iso-Sensitest Broth (ISB) supplemented with 20 μM of apoT was used to suppress the trailing effect. Tested isolates were collected frommulti-sites in North America, Europe and other regions from 2009 to 2011. Approximately 34% and 23% of tested isolates were resistant to ceftazidime and meropenem respectively. Results. ’266 showed potent in vitro activity against a broad spectrum of Gramnegative bacteria. MIC90 of ’266 against 1086 strains of Gram-negative bacteria was 2 μg/mL. MIC90 against Pseudomonas aeruginosa, Stenotrophomonas maltophilia and most of Enterobacteriaceae were 1 μg/mL or less, and MIC90 against A. baumannii was 2 μg/mL. These results demonstrated the potent antimicrobial activity of ’266 against a variety of Gram-negative bacteria including strains non-susceptible to ceftazidime, meropenem, levofloxacin or ciprofloxacin.