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Multidrug-resistantKlebsiella pneumoniae carbapenemase (KPC)-producingEnterobacteriaceae are endemic to hospitals in New York City and other regions. RPX7009 is a novel β-lactamase inhibitor with activity against serine carbapenemases. We tested the activity of meropenem plus RPX7009 against 4,500 recent Gram-negative clinical isolates from 11 New York City hospitals. The meropenem-RPX7009 combination was found to have excellentin vitro activity againstEscherichia coli ,K. pneumoniae , andEnterobacter spp., including multidrug-resistant (MDR) KPC-producing strains. Overall, 131/133 (98.5%) KPC-producingEnterobacteriaceae strains were inhibited by meropenem (≤1 μg/ml) plus RPX7009 (8 μg/ml). In a limited number of strains, the combination appeared to have reduced activity against KPC-producingK. pneumoniae isolates with diminishedompK35 andompK36 expression. The addition of RPX7009 did not affect the activity of meropenem againstAcinetobacter baumannii andPseudomonas aeruginosa . The meropenem-RPX7009 combination shows promise as a novel agent against KPC-producingEnterobacteriaceae and deserves further study. Other approaches will be needed to address multidrug-resistantA. baumannii andP. aeruginosa , which typically possess different mechanisms of carbapenem resistance.

Activity of Meropenem Combined with RPX7009, a Novel β-Lactamase Inhibitor, against Gram-Negative Clinical Isolates in New York City