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Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)

OBJECTIVES: Meropenem/vaborbactam has been approved in Europe for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP) and bacteraemia among other indications. Vaborbactam is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapen...

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Autores principales: Shortridge, Dee, Carvalhaes, Cecilia, Deshpande, Lalitagauri, Castanheira, Mariana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446919/
https://www.ncbi.nlm.nih.gov/pubmed/34302173
http://dx.doi.org/10.1093/jac/dkab252
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author Shortridge, Dee
Carvalhaes, Cecilia
Deshpande, Lalitagauri
Castanheira, Mariana
author_facet Shortridge, Dee
Carvalhaes, Cecilia
Deshpande, Lalitagauri
Castanheira, Mariana
author_sort Shortridge, Dee
collection PubMed
description OBJECTIVES: Meropenem/vaborbactam has been approved in Europe for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP) and bacteraemia among other indications. Vaborbactam is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC) enzymes, but not class B or D carbapenemases. We analysed the activity of meropenem/vaborbactam and comparators against 6846 Enterobacterales and 3567 Pseudomonas aeruginosa isolates from patients hospitalized with pneumonia (PHP), including VAP. METHODS: Isolates from PHP were consecutively collected during 2014–19 from 42 European hospitals located in 21 countries and susceptibility tested using the broth microdilution method. Carbapenem-resistant Enterobacterales (CRE) isolates were molecularly characterized to identify their carbapenem-resistance mechanisms. EUCAST (2020) interpretive criteria were used. RESULTS: The most common Gram-negative pathogens isolated from PHP were P. aeruginosa (n = 3567), K. pneumoniae (n = 1877) and Escherichia coli (n = 1646). Overall, 98.0% of Enterobacterales and 82.1% of P. aeruginosa were susceptible to meropenem/vaborbactam, with 99.8% of Enterobacterales and 89.7% of P. aeruginosa in Western Europe (WE) and 92.7% of Enterobacterales and 69.1% of P. aeruginosa in Eastern Europe (EE). CRE were more common in EE (15.1%) than WE (2.1%). KPC was the most common carbapenemase in WE, while OXA-48-like was the most common carbapenemase in EE. Meropenem/vaborbactam susceptibility was 63.0% for all CRE (92.2% in WE and 51.5% in EE). Meropenem/vaborbactam inhibited 99.1% of KPC-producing isolates and 40.5% of OXA-48-like-producing isolates. CONCLUSIONS: These in vitro data demonstrate that meropenem/vaborbactam has potent activity against isolates from PHP, including isolates producing KPC, and may be a useful treatment option for PHP, including VAP.
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spelling pubmed-84469192021-09-20 Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19) Shortridge, Dee Carvalhaes, Cecilia Deshpande, Lalitagauri Castanheira, Mariana J Antimicrob Chemother Original Research OBJECTIVES: Meropenem/vaborbactam has been approved in Europe for the treatment of hospital-acquired bacterial pneumonia, ventilator-associated pneumonia (VAP) and bacteraemia among other indications. Vaborbactam is an inhibitor of class A and C β-lactamases, including Klebsiella pneumoniae carbapenemase (KPC) enzymes, but not class B or D carbapenemases. We analysed the activity of meropenem/vaborbactam and comparators against 6846 Enterobacterales and 3567 Pseudomonas aeruginosa isolates from patients hospitalized with pneumonia (PHP), including VAP. METHODS: Isolates from PHP were consecutively collected during 2014–19 from 42 European hospitals located in 21 countries and susceptibility tested using the broth microdilution method. Carbapenem-resistant Enterobacterales (CRE) isolates were molecularly characterized to identify their carbapenem-resistance mechanisms. EUCAST (2020) interpretive criteria were used. RESULTS: The most common Gram-negative pathogens isolated from PHP were P. aeruginosa (n = 3567), K. pneumoniae (n = 1877) and Escherichia coli (n = 1646). Overall, 98.0% of Enterobacterales and 82.1% of P. aeruginosa were susceptible to meropenem/vaborbactam, with 99.8% of Enterobacterales and 89.7% of P. aeruginosa in Western Europe (WE) and 92.7% of Enterobacterales and 69.1% of P. aeruginosa in Eastern Europe (EE). CRE were more common in EE (15.1%) than WE (2.1%). KPC was the most common carbapenemase in WE, while OXA-48-like was the most common carbapenemase in EE. Meropenem/vaborbactam susceptibility was 63.0% for all CRE (92.2% in WE and 51.5% in EE). Meropenem/vaborbactam inhibited 99.1% of KPC-producing isolates and 40.5% of OXA-48-like-producing isolates. CONCLUSIONS: These in vitro data demonstrate that meropenem/vaborbactam has potent activity against isolates from PHP, including isolates producing KPC, and may be a useful treatment option for PHP, including VAP. Oxford University Press 2021-07-23 /pmc/articles/PMC8446919/ /pubmed/34302173 http://dx.doi.org/10.1093/jac/dkab252 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Shortridge, Dee
Carvalhaes, Cecilia
Deshpande, Lalitagauri
Castanheira, Mariana
Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)
title Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)
title_full Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)
title_fullStr Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)
title_full_unstemmed Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)
title_short Activity of meropenem/vaborbactam and comparators against Gram-negative isolates from Eastern and Western European patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)
title_sort activity of meropenem/vaborbactam and comparators against gram-negative isolates from eastern and western european patients hospitalized with pneumonia including ventilator-associated pneumonia (2014–19)
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446919/
https://www.ncbi.nlm.nih.gov/pubmed/34302173
http://dx.doi.org/10.1093/jac/dkab252
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