title: 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.
authors.affiliation: Division of Infectious Diseases, SUNY Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Amabel
authors.initials: A
authors.lastname: Lapuebla
authors.affiliation: Division of Infectious Diseases, SUNY Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Abdallah
authors.affiliation: Division of Infectious Diseases, SUNY Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Olawole
authors.initials: O
authors.lastname: Olafisoye
authors.affiliation: The Dr. James J. Rahal, Jr., Division of Infectious Diseases, New York Hospital Queens, Flushing, New York, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cortes
authors.affiliation: The Dr. James J. Rahal, Jr., Division of Infectious Diseases, New York Hospital Queens, Flushing, New York, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Urban
authors.affiliation: Division of Infectious Diseases, SUNY Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: John
authors.initials: J
authors.lastname: Quale
authors.affiliation: Division of Infectious Diseases, SUNY Downstate Medical Center, Brooklyn, New York, USA dlandman@downstate.edu.
authors.forename: David
authors.initials: D
authors.lastname: Landman
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001897:Boronic Acids / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004359:Drug Therapy, Combination / Q000379:methods; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology*; D006761:Hospitals; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests / Q000379:methods; D009519:New York City; D013845:Thienamycins / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001897:Boronic Acids; D006573:Heterocyclic Compounds, 1-Ring; C000599945:RPX7009; D013845:Thienamycins; D065093:beta-Lactamase Inhibitors; D000077731:Meropenem