Session: Poster Abstract Session: Antibacterial Susceptibility Surveillance
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:
4,109 clinical isolates collected in 2015 in NA (1,148) and EU (2,961) 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-non-susceptible (CarbNS) isolates were defined as non-susceptible 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 – 1 µg/mL for the species shown below, and 1 – 4 µg/mL for the CarbNS subsets. Greater 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.
|
| MIC90 | ||||||
Organism | N | S-649266 | FEP | CZA | C/T | CIP | CST | MEM |
A. baumannii | 306 | 1 | 64 | >64 | >64 | >8 | 1 | >64 |
A. baumannii, CarbNS | 179 | 1 | >64 | >64 | >64 | >8 | 2 | >64 |
Enterobacteriaceae | 2819 | 1 | 16 | 0.5 | 4 | >8 | 1* | 0.12 |
Enterobacteriaceae, CarbNS | 71 | 4 | >64 | >64 | >64 | >8 | >8* | >64 |
P. aeruginosa | 686 | 0.5 | 16 | 8 | 4 | >8 | 2 | 16 |
P. aeruginosa, CarbNS | 165 | 1 | 64 | 64 | >64 | >8 | 1 | >64 |
* Serratia spp. were excluded due to intrinsic non-susceptibility to colistin, N=2,349 for Enterobacteriaceae, N=67 for CarbNS Enterobacteriaceae
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.
Disclosures:
M. Hackel,
IHMA, Inc.:
Independent Contractor
,
Research support
R. Echols, Shionogi Inc.: Employee , Salary
D. Sahm, IHMA, Inc.: Independent Contractor , Research support