Imipenem/relebactam activity compared to other antimicrobials against non-MBL-producing carbapenem-resistant Enterobacteriaceae from an academic medical center

Background: Carbapenem-resistant Enterobacteriaceae (CRE) cause significant mortality and are resistant to most antimicrobial agents. Imipenem/relebactam, a novel beta-lactam/beta-lactamase inhibitor combination, and 16 other antimicrobials were evaluated against non-metallo-beta-lactamase-producing carbapenem-resistant Enterobacteriaceae clinical isolates from a United States tertiary academic medical center. Objectives: To evaluate imipenem/relebactam and other commonly utilised antimicrobial agents against carbapenem-resistant Enterobacteriaceae. Methods: Clinical isolates (n = 96) resistant to ertapenem or meropenem by BD Phoenix (Becton, Dickinson and Company, Franklin Lakes, NJ, USA) and negative for metallo-beta-lactamase-production by an EDTA (Sigma-Aldrich Corp., St. Louis, MO, USA)/phenylboronic acid (Sigma-Aldrich Corp., St. Louis, MO, USA) disk diffusion assay were identified and collected from January 2012 to January 2017. In vitro susceptibility by broth microdilution was performed according to CLSI guidelines using CLSI susceptibility breakpoints for 17 antimicrobials (Sigma-Aldrich Corp., St. Louis, MO, USA). Results: CRE primarily produced Klebsiella pneumoniae carbapenemase (KPC) and consisted primarily of K. pneumoniae (55%) and Enterobacter spp. (25%), followed by Citrobacter spp. (10%), Escherichia coli (5%), and others (5%). CRE were most susceptible to imipenem/relebactam (100%), followed by amikacin (85%), tigecycline (82%), and polymyxin B/colistin (65%). The median reduction of imipenem minimum inhibitory concentrations (MICs) of non-MBL-producing CRE was 16-fold but ranged from 0.5 to >512-fold. The MIC₅₀, MIC₉₀ and MIC range of imipenem/relebactam was 0.5/4, 1/4 and 0.06/4-1/4 mg/L, respectively. Conclusions: Imipenem/relebactam exhibits excellent activity against CRE that produce KPC.