In-vitro activity of imipenem/relebactam and key β-lactam agents against Gram-negative bacilli isolated from lower respiratory tract infection samples of intensive care unit patients - SMART Surveillance United States 2015-2017

beta-lactam- and multi-drug-resistant (MDR) Gram-negative bacilli frequently cause lower respiratory tract infections (LRTIs) in patients housed in intensive care units (ICUs). Relebactam, a novel diazabicyclooctane inhibitor of Ambler class A and C beta-lactamases, in combination with imipenem-cilastatin was approved by the US Food and Drug Administration in July 2019 for the treatment of adults with complicated intra-abdominal infections and complicated urinary tract infections. A phase III study of imipenem/relebactam for the treatment of patients with respiratory tract infections, including antimicrobial-resistant Gram-negative infections, has also been completed. The Clinical and Laboratory Standards Institute's broth microdilution methodology was used to determine minimum inhibitory concentrations against non-Proteeae Enterobacteriaceae (NPE) and Pseudomonas aeruginosa collected from ICU patients with LRTIs at 26 US hospitals in 2015-2017. Percent susceptibilities to imipenem/relebactam were 97.0%, 66.4% and 98.1%, respectively, for all NPE (n=1298), imipenem-non-susceptible NPE (n=113, of which 71% were Serratia marcescens) and MDR NPE (n=206), and 92.2%, 77.2% and 79.6%, respectively, for all P. aeruginosa (n=638), imipenem-non-susceptible P. aeruginosa (n=219) and MDR P. aeruginosa (n=225). Percent susceptibilities to imipenem/relebactam were 98.0-98.6% for cefepime-, ceftazidime- and piperacillin-tazobactam-nonsusceptible NPE and 77.8-82.5% for cefepime-, ceftazidime- and piperacillin-tazobactam-non-susceptible P. aeruginosa. Generally, only slight variations in susceptibility were observed across US census regions. Imipenem/relebactam may provide a valuable therapeutic option for the treatment of ICU patients with LRTI caused by Gram-negative bacilli resistant to commonly used beta-lactams, as it demonstrated potent in-vitro activity against the majority of tested beta-lactam-non-susceptible and MDR Gram-negative bacilli from ICU patients with LRTIs in US hospitals. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.