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

Abstract

Multidrug-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae 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 excellent in vitro activity against Escherichia coli, K. pneumoniae, and Enterobacter spp., including multidrug-resistant (MDR) KPC-producing strains. Overall, 131/133 (98.5%) KPC-producing Enterobacteriaceae 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-producing K. pneumoniae isolates with diminished ompK35 and ompK36 expression. The addition of RPX7009 did not affect the activity of meropenem against Acinetobacter baumannii and Pseudomonas aeruginosa. The meropenem-RPX7009 combination shows promise as a novel agent against KPC-producing Enterobacteriaceae and deserves further study. Other approaches will be needed to address multidrug-resistant A. baumannii and P. aeruginosa, which typically possess different mechanisms of carbapenem resistance.