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.
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