Synergistic activities of meropenem double and triple combinations against carbapenemase-producing Enterobacteriaceae

The increasing emergence of carbapenemase-producing Enterobacteriaceae poses a considerable threat to global health as only limited treatment options are available and has therefore led to efforts to discover antibiotic combination regimens effective. The aim of this study was to evaluate in vitro synergistic activity of 10 meropenem double and triple combinations against the 5 most frequently encountered carbapenemases-producing Enterobacteriaceae. Broth microdilution assays showed that the meropenem and ertapenem combination was the most efficient regimen of the double combinations tested (>5-log2 fold decrease). The triple combination of meropenem, polymyxin and rifampin exhibited highest synergistic activity of the triple combinations. The divergent reports on synergistic activity of antibiotic combinations suggest that it may not be possible to predict synergy based on carbapenemase type alone. Consequently, we recommend that in vitro evaluation of synergistic activity of antibiotic combinations against carbapenemase-producing Enterobacteriaceae is performed on every isolate to ensure effective treatment regimens.