Activity of meropenem combined with RPX7009, a novel β-lactamase inhibitor, against Gram-negative clinical isolates in New York City.

Activity of meropenem combined with RPX7009, a novel β-lactamase inhibitor, against Gram-negative clinical isolates in New York City.

Antimicrob Agents Chemother. 2015 Jun 1;

Authors: Lapuebla A, Abdallah M, Olafisoye O, Cortes C, Urban C, Quale J, Landman D

Abstract
Multidrug-resistant 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 4500 recent Gram-negative clinical isolates from 11 New York City hospitals. The meropenem/RPX7009 combination was found to have excellent in-vitro activity against E. coli, K. pneumoniae, and Enterobacter spp., including MDR KPC-producing strains. Overall, 131/133 (98.5%) of KPC-producing Enterobacteriaceae 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 A. baumannii and P. 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.

PMID: 26033723 [PubMed - as supplied by publisher]