In Vitro Antibacterial Activity of S-649266 against Gram-negative Clinical Strains Collected in North America and Europe, 2015

Abstract

Background. S-649226 is a novel parenteral siderophore cephalosporin with potent activity against Gram-negative pathogens including carbapenem-resistant isolates and is currently in clinical development by Shionogi & Co., Ltd. This study evaluated the in vitro activity of S-649266 and comparator agents against relevant clinical isolates collected in 2015 in North America (NA) and Europe (EU). Methods. A total of 4109 clinical isolates collected in 2015 in NA (1148) and EU (2961) comprising 23 species were tested. MICs were determined for S-649266, cefepime (FEP), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), ciprofloxacin (CIP), colistin (CST), and meropenem (MEM) by CLSI broth microdilution and interpreted following CLSI 2016 guidelines, with the exception that S-649226 was tested in iron-depleted media. Carbapenem-nonsusceptible (CarbNS) isolates were defined as nonsusceptible to meropenem using CLSI breakpoints. Quality control testing was performed on each day of testing. Results. The MIC90 values of the test compounds are shown in the table. The S-649266 MIC90 ranged from 0.5 to 1 μg/mL for the species shown below, and from 1 to 4 μg/mL for the CarbNS subsets. More than 99% of isolates had MIC values ≤4 μg/mL. In particular, the activity of S-649266 was significantly potent compared to the other the test compounds against the CarbNS subsets. Conclusion. S-649266 demonstrated good in vitro potency against A. baumannii, Enterobacteriaceae, and P. aeruginosa, including CarbNS isolates collected from Europe and North America. Overall, S-649266 showed promising activity against this collection of recent clinical isolates. (Table Presented) .