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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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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
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author Patel, Twisha S
Kaye, Keith S
Krishnan, Jay
Marshall, Vince
Mills, John
Albin, Owen
Young, Carol
Smith, Aaron
Lephart, Paul
M. Pogue, Jason
author_facet Patel, Twisha S
Kaye, Keith S
Krishnan, Jay
Marshall, Vince
Mills, John
Albin, Owen
Young, Carol
Smith, Aaron
Lephart, Paul
M. Pogue, Jason
author_sort Patel, Twisha S
collection PubMed
description 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.
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spelling pubmed-68107882019-10-28 521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa Patel, Twisha S Kaye, Keith S Krishnan, Jay Marshall, Vince Mills, John Albin, Owen Young, Carol Smith, Aaron Lephart, Paul M. Pogue, Jason Open Forum Infect Dis Abstracts 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. Oxford University Press 2019-10-23 /pmc/articles/PMC6810788/ http://dx.doi.org/10.1093/ofid/ofz360.590 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Patel, Twisha S
Kaye, Keith S
Krishnan, Jay
Marshall, Vince
Mills, John
Albin, Owen
Young, Carol
Smith, Aaron
Lephart, Paul
M. Pogue, Jason
521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa
title 521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa
title_full 521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa
title_fullStr 521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa
title_full_unstemmed 521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa
title_short 521. Comparative In Vitro Activity of Meropenem/Vaborbactam and Meropenem Against a Collection of Real-World Clinical Isolates of Pseudomonas aeruginosa
title_sort 521. comparative in vitro activity of meropenem/vaborbactam and meropenem against a collection of real-world clinical isolates of pseudomonas aeruginosa
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810788/
http://dx.doi.org/10.1093/ofid/ofz360.590
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