1828. In Vitro Antibacterial Activity of S-649266 against Gram-negative Clinical Strains Collected in North America and Europe, 2015
Session: Poster Abstract Session: Antibacterial Susceptibility Surveillance
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • P15_Shionogi_S_266 surveillance_v01 final.pdf (659.3 kB)
  • 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.

    Meredith Hackel, PhD, MPH1, Masakatsu Tsuji, Ph.D2, Roger Echols, MD, FIDSA3 and Dan Sahm, PhD1, (1)International Health Management Associates, Inc., Schaumburg, IL, (2)Drug Discovery & Disease Research Laboratory, SHIONOGI & CO., LTD., Osaka, Japan, (3)ID3C, Easton, CT

    Disclosures:

    M. Hackel, IHMA, Inc.: Independent Contractor , Research support

    M. Tsuji, Shionogi & Co Ltd: Employee , Salary

    R. Echols, Shionogi Inc.: Employee , Salary

    D. Sahm, IHMA, Inc.: Independent Contractor , Research support

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.