In vitro activity of imipenem-relebactam against gram-negative bacilli isolated from patients with lower respiratory tract infections in the United States in 2015 - Results from the SMART global surveillance program

•The novel β-lactamase inhibitor relebactam was tested in combination with imipenem against non-Proteeae Enterobacteriaceae (NPE) and P. aeruginosa.•Isolates were collected from lower respiratory tract infections in the US in 2015.•Imipenem-relebactam and imipenem susceptibilities were 97.2% and 91.6% for NPE and 93.1% and 68.1% for P. aeruginosa, respectively.•Relebactam restored imipenem susceptibility to 66.7% and 78.5% of imipenem-non-susceptible NPE and P. aeruginosa.

The β-lactamase inhibitor relebactam inactivates class A β-lactamases, including KPC-type carbapenemases, and class C β-lactamases. Relebactam combined with imipenem is in clinical development for several indications, including hospital-acquired and ventilator-associated pneumonia. Employing CLSI-defined broth microdilution methodology, we evaluated the activities of imipenem-relebactam (using imipenem MIC breakpoints) and comparators against non-Proteeae Enterobacteriaceae (n = 853) and Pseudomonas aeruginosa (n = 598) isolated from lower respiratory tract infection samples in 20 hospital laboratories in the United States participating in the 2015 SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Imipenem-relebactam and imipenem susceptibilities were 97.2% and 91.6% for non-Proteeae Enterobacteriaceae and 93.1% and 68.1% for P. aeruginosa. Relebactam restored imipenem susceptibility to 66.7% and 78.5% of imipenem-non-susceptible non-Proteeae Enterobacteriaceae isolates (n = 72) and P. aeruginosa (n = 191), respectively. Further development of imipenem-relebactam as therapy for lower respiratory tract infections is warranted given relebactam's ability to restore activity to imipenem against non-susceptible non-Proteeae Enterobacteriaceae and P. aeruginosa.