2243. Global Surveillance of the Activity of Sulbactam combined with the Novel β-lactamase Inhibitor ETX2514 against Clinical Isolates of Acinetobacter baumannii from 2014
Session: Poster Abstract Session: New Antibiotics in Development
Saturday, October 29, 2016
Room: Poster Hall
  • Hackel_SUL-ETX2514_surveillance.pdf (949.1 kB)
  • Background: Multidrug-resistant Acinetobacter baumannii infections are considered a serious threat by the Centers for Disease Control and other government agencies. They are among the most difficult to treat and are associated with high mortality rates due to the limited number of effective therapies available and inappropriate initial treatment choice. The novel diazabicyclooctenone β-lactamase inhibitor effectively restores the antibacterial activity of sulbactam against multidrug resistant (MDR) A. baumannii due to its potent inhibition of Class A, C and D serine β-lactamases, which are commonly found in this organism.

    Methods: The in vitro activity of sulbactam-ETX2514 and comparator antibiotics was determined against clinical isolates of Acinetobacter baumannii using the broth microdilution methodology recommended by the Clinical and Laboratory Standards Institute (CLSI). A total of 1,131 isolates were obtained from hospitalized patients in 151 medical centers within 38 countries during the year 2014.

    Results: The activity of sulbactam-ETX2514 was 16-fold higher than that of sulbactam alone (MIC50 values of 1 and 16 mg/L, respectively, and MIC90 values of 4 and 64 mg/L, respectively). This increased activity was maintained against all subsets of resistant phenotypes including meropenem-resistant, colistin-resistant, multidrug-resistant, ESBL-positive, and non-MBL isolates, as well as isolates containing Ambler class D β-lactamases. There was a 2-fold lower MIC for sulbactam-ETX2514 compared to sulbactam (32 vs 64 mg/L) alone against the single A. baumannii isolate found to carry a gene encoding a metallo-β-lactamase. MIC50 and MIC90 values were also remarkably consistent across subsets of isolates from different sources, from pediatric patients, and from the five geographic regions.

    Conclusion: The activity of sulbactam-ETX2514 observed in this study suggests that further in vitro and clinical investigation is warranted to explore the utility of this agent against this difficult-to-treat nosocomial pathogen.

    Alita Miller, PhD1, Meredith Hackel, PhD, MPH2, Samuel Bouchillon, MD2, Boudewijn Dejonge, PhD3, Ruben Tommasi, PhD1 and John Mueller, PhD1, (1)Entasis Therapeutics, Waltham, MA, (2)International Health Management Associates, Inc., Schaumburg, IL, (3)AstraZeneca Pharmaceuticals, Waltham, MA


    A. Miller, Entasis Therapeutics: Employee , Salary

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

    S. Bouchillon, Entasis Therapeutics: Research Contractor , fee for service

    B. Dejonge, None

    R. Tommasi, Entasis Therapeutics: Employee , Salary
    Entasis Therapeutics: Employee , Salary

    J. Mueller, Entasis Therapeutics: Employee and Shareholder , Salary

    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.