Effect of increasing meropenem MIC on the killing activity of meropenem in combination with amikacin or polymyxin B against MBL- and KPC-producing Enterobacter cloacae

Carbapenem resistant Enterobacteriaceae (CRE) are a growing threat worldwide. Infections caused by these organisms have exhibited high rates of mortality (50%) for which there is no standard of care and a dearth of clinical trials. Most in vitro data on CRE focus on Klebsiella pneumoniae, but it is known that effective therapy may depend on species or even strain. To address this, meropenem, amikacin, and polymyxin B alone and in combination were evaluated by time kill against four carbapenem-producing Enterobacter cloacae clinical isolates representing a range of meropenem nonsusceptibility (2-32 mg/L) and resistance mechanisms (KPC 2 and/or VIM 1). As meropenem minimum inhibitory concentration (MIC) increased, bactericidal activity and synergy were maintained for 48 hours in isolates exposed to meropenem and amikacin, but synergy and bactericidal activity were not maintained in all isolates exposed to meropenem and polymyxin B.