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521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa

BACKGROUND: Meropenem/vaborbactam (MV) is a carbapenem and boronic acid–based β-lactamase inhibitor combination product with potent in vitro activity against Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. As carbapenem resistance in Pseudomonas aeruginosa (PSA) is primarily driven...

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Detalles Bibliográficos
Autores principales: Patel, Twisha S, Kaye, Keith S, Krishnan, Jay, Marshall, Vince, Mills, John, Albin, Owen, Young, Carol, Smith, Aaron, Lephart, Paul, M. Pogue, Jason
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810788/
http://dx.doi.org/10.1093/ofid/ofz360.590
Descripción
Sumario:BACKGROUND: Meropenem/vaborbactam (MV) is a carbapenem and boronic acid–based β-lactamase inhibitor combination product with potent in vitro activity against Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. As carbapenem resistance in Pseudomonas aeruginosa (PSA) is primarily driven by porin mutations, efflux pumps, or infrequently by metallo-β-lactamases, vaborbactam is not expected to improve the in vitro activity of meropenem (MEM) against this pathogen. However, limited data currently exists assessing the comparative in vitro activity of MEM and MV. The purpose of this study was to compare the in vitro activity of MV and MEM against a large real-world sample of clinical isolates of PSA where both MV and MEM are routinely tested on all isolates. METHODS: All cultures from patient infections with PSA from May 2018 to February 2019 at Michigan Medicine were included. Minimum inhibitory concentrations (MICs) were determined using TREK broth microdilution panels and isolates were considered susceptible to MV if the MIC was ≤4 mg/L and MEM if the MIC was ≤2 mg/L. RESULTS: A total of 2,967 isolates of PSA from clinical specimens were included. 80.5% of isolates were susceptible to MEM (MIC(50) ≤1 mg/L and MIC(90) 8 mg/L, range ≤1 to >32 mg/L) at a breakpoint of ≤2 mg/L and 86.3% at a breakpoint of ≤4 mg/L; whereas 90.8% of isolates were susceptible to MV (MIC(50) ≤1 mg/L and MIC(90) 4 mg/L, range ≤1 to >8 mg/L). Of those displaying MEM MIC >2 mg/L, 53% (n = 308) were susceptible to MV. Of those displaying MEM MIC >4 mg/L, 33.7% (n = 137) were susceptible to MV. Although the majority of MIC discordances in MEM-R/MV-S isolates were 1–2 doubling dilutions, 52 (38%) isolates had their meropenem MIC decreased ≥3 doubling dilutions by the addition of vaborbactam suggesting significant inhibitory activity (Table 1). CONCLUSION: We found a surprising number of PSA isolates with discordant MV and MEM susceptibility at Michigan Medicine. Further exploration of mechanisms of meropenem resistance in these isolates is warranted. [Image: see text] DISCLOSURES: All authors: No reported disclosures.