Background: Relebactam (REL), formerly MK-7655, is a β-lactamase inhibitor of class A and C β-lactamases that is in clinical development in combination with imipenem (IMI). In this study, we evaluated the activity of IMI/REL against gram-negative bacilli and resistant phenotypes collected in the United States as part of the SMART surveillance program from patients with lower respiratory tract infections (RTI) in ICUs, where antimicrobial resistance is typically higher than in non-ICU wards.
Methods: In 2015-2017, 26 hospitals in the US each collected up to 100 consecutive gram-negative pathogens from RTI per year. Antimicrobial susceptibility was determined for 1,298 non-Proteeae Enterobacteriaceae (NPE) and 638 P. aeruginosa isolates collected in ICUs, using CLSI broth microdilution and breakpoints; for comparison purposes, the IMI susceptible breakpoint was applied to IMI/REL. Proteeae were excluded due to intrinsic non-susceptibility to IMI. Susceptibility was calculated for the 4 United States census regions and overall.
Results: Susceptibility of NPE was lowest in the Midwest to ceftazidime (81%) and cefepime (87%) and highest in the Northeast (88 and 94%, respectively); susceptibility to imipenem (89-93%) and piperacillin-tazobactam (86-90%) showed less variability across regions. Susceptibility of P. aeruginosa to the 4 agents was lowest in the West region (57-65%) and highest in the Northeast (68-76%). Susceptibilities to IMI/REL of NPE and P. aeruginosa as well as of phenotypes nonsusceptible (NS) to β-lactams are shown below.
Conclusion: The studied β-lactams showed some variability in activity against pathogens from RTI patients in ICUs across census regions, whereas IMI/REL maintained activity in all regions against NPE (>96%) and P. aeruginosa (90-95%). IMI/REL remained active against ≥98% of resistant phenotypes of NPE, except the imipenem-NS subset (67.5% susceptible), which was composed mainly of Serratia spp., and remained active against 77-82% of resistant phenotypes of P. aeruginosa, including 77.2% of imipenem-NS isolates. IMI/REL may provide a valuable therapeutic option for the treatment of ICU patients with respiratory tract infections caused by organisms resistant to commonly used β-lactams.
D. Hoban, IHMA, Inc.: Employee , Salary . Merck: Consultant , Consulting fee .
M. Hackel, IHMA, Inc.: Employee , Salary . Merck: Consultant , Consulting fee .
K. Young, Merck: Employee and Shareholder , Dividends and Salary .
M. Motyl, Merck: Employee and Shareholder , Dividends and Salary .
D. Sahm, IHMA, Inc.: Employee , Salary . Merck: Consultant , Consulting fee .