Activity of Imipenem/Relebactam on Klebsiella Pneumoniae With Different Mechanisms of Imipenem Non-Susceptibility

Background and objectives: imipenem/relebactam (imp/r) is a newly fda approved β-lactam/β-lactamase inhibitor combination. relebactam ability to restore imp activity could differ according to the cause of imipenem non-susceptibility. therefore, we investigated the in-vitro activity of imp/r against klebsiella pneumoniae with different mechanisms of imi- penem non-susceptibility. materials and methods: imipenem-nonsusceptible (imp-ns) k. pneumoniae isolates were collected and characterized for β-lactamase encoding genes by multiplex pcr. for imp-ns carbapenemase-negative isolates, study of ompk35 & ompk36 gene expression was performed by reverse transcription-pcr while efflux pump activity was studied by minimum inhibitory concentration (mic) reduction assay using efflux pump inhibitor. susceptibility testing of k. pneumoniae to imp and imp/r were achieved by broth microdilution (bmd) method. results: during the study period, 140 isolates of imp-ns k. pneumoniae were collected. bmd method showed that relebactam restored imp susceptibility in 100%, 60% and 49% of isolates that only harbor ampc, extended spectrum beta lactamase (esbl) and carbapenemases, respectively. imp/r was most potent against all bla kpc and 50% of bla _producing isolates. no demonstrable activity of imp/r against k. pneumoniae harboring metallo-β-lactamases (mbls). out of 18 isolates with imp non-suceptibility due to porins loss with overproduction of esbl and/or ampc, 14 (77.7%) isolates were imp/r sus- ceptible. imp/r showed no activity against isolates with only efflux pump hyperactivity. conclusion: relebactam could restore ipm activity in kpc or ampc-producing imp/ns k. pneumoniae but with no activity against mbl- producing isolates. relebactam activity against isolates harbouring-bla oxa-48 or with altered ompk35 & ompk36 gene expression and efflux pump hyperactivity need further studies. therefore, using imp/r antibiotic in the treat- ment of infections caused by imp/ns k. pneumoniae should be based on its molecular profile of imp resistance to optimize the utility of imp/r.