Sulbactam Combined With the Novel β-lactamase Inhibitor ETX2514 for the Treatment of Multidrug-Resistant Acinetobacter baumannii Infections

Abstract

Background. Multidrug-resistant (MDR) Acinetobacter baumannii infections are of great concern due to high mortality rates and limited number of treatment options. β-lactamase (BL) expression, especially class D, is an important resistance mechanism in this organism. The novel BL inhibitor ETX2514 has potent activity against class A, C, and D serine BLs. The MIC90 of sulbactam (SUL) in the presence of ETX2514 is 4 mg/L against a large, globally diverse set of MDR A. baumannii clinical isolates from 2014. In this study, we investigate the mechanism of synergy of this combination alone or in the presence of imipenem (IPM) or meropenem (MEM), whose spectra of target inhibition vary across bacterial species