Activity of imipenem/relebactam on 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 activity of IMP/R against with different mechanisms of imipenem non-susceptibility.

MATERIALS AND METHODS

Imipenem-nonsusceptible (IMP-NS) isolates were collected and characterized for β-lactamase encoding genes by multiplex PCR. For IMP-NS carbapenemase-negative isolates, study of & 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 to IMP and IMP/R were achieved by broth microdilution (BMD) method.

RESULTS

During the study period, 140 isolates of IMP-NS 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 and 50% of _producing isolates. No demonstrable activity of IMP/R against 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 susceptible. 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 but with no activity against MBL producing isolates. Relebactam activity against isolates harbouring- or with altered & gene expression and efflux pump hyperactivity need further studies. Therefore, using IMP/R antibiotic in the treatment of infections caused by IMP/NS should be based on its molecular profile of IMP resistance to optimize the utility of IMP/R.