Bactericidal efficacy of meropenem in combination with cefmetazole against IMP-producing carbapenem-resistant Enterobacteriaceae

Abstract

Objective: Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against Imipenemase (IMP)-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring bla IMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring bla IMP-6 (8 E. coli and 5 K. pneumoniae isolates). Results: Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both bla IMP-1 and bla IMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.