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Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa

Multidrug resistant (MDR) P. aeruginosa accounts for 35% of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF). The usefulness of β-lactam antibiotics for treating CF, such as carbapenems and later generation cephalosporins, is limited by the development of ant...

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Autores principales: Haines, Robbie R., Putsathit, Papanin, Hammer, Katherine A., Tai, Anna S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547053/
https://www.ncbi.nlm.nih.gov/pubmed/36207358
http://dx.doi.org/10.1038/s41598-022-21101-x
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author Haines, Robbie R.
Putsathit, Papanin
Hammer, Katherine A.
Tai, Anna S.
author_facet Haines, Robbie R.
Putsathit, Papanin
Hammer, Katherine A.
Tai, Anna S.
author_sort Haines, Robbie R.
collection PubMed
description Multidrug resistant (MDR) P. aeruginosa accounts for 35% of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF). The usefulness of β-lactam antibiotics for treating CF, such as carbapenems and later generation cephalosporins, is limited by the development of antibacterial resistance. A proven treatment approach is the combination of a β-lactam antibiotic with a β-lactamase inhibitor. New β-lactam/β-lactamase inhibitor combinations are available, but data are lacking regarding the susceptibility of MDR CF-associated P. aeruginosa (CFPA) to these new combination therapies. In this study we determined MIC values for three new combinations; imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), and ceftolozane-tazobactam (C/T) against MDR CFPA (n = 20). The MIC(90) of I-R, CZA, and C/T was 64/4, 32/4, and 16/8 (all µg/mL), respectively. The susceptibility of isolates to imipenem was not significantly improved with the addition of relebactam (p = 0.68). However, susceptibility to ceftazidime was significantly improved with the addition of avibactam (p < 0.01), and the susceptibility to C/T was improved compared to piperacillin/tazobactam (p < 0.05) These data provide in vitro evidence that I-R may not be any more effective than imipenem monotherapy against MDR CFPA. The pattern of susceptibility observed for CZA and C/T in the current study was similar to data previously reported for non-CF-associated MDR P. aeruginosa.
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spelling pubmed-95470532022-10-09 Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa Haines, Robbie R. Putsathit, Papanin Hammer, Katherine A. Tai, Anna S. Sci Rep Article Multidrug resistant (MDR) P. aeruginosa accounts for 35% of all P. aeruginosa isolated from respiratory samples of patients with cystic fibrosis (CF). The usefulness of β-lactam antibiotics for treating CF, such as carbapenems and later generation cephalosporins, is limited by the development of antibacterial resistance. A proven treatment approach is the combination of a β-lactam antibiotic with a β-lactamase inhibitor. New β-lactam/β-lactamase inhibitor combinations are available, but data are lacking regarding the susceptibility of MDR CF-associated P. aeruginosa (CFPA) to these new combination therapies. In this study we determined MIC values for three new combinations; imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), and ceftolozane-tazobactam (C/T) against MDR CFPA (n = 20). The MIC(90) of I-R, CZA, and C/T was 64/4, 32/4, and 16/8 (all µg/mL), respectively. The susceptibility of isolates to imipenem was not significantly improved with the addition of relebactam (p = 0.68). However, susceptibility to ceftazidime was significantly improved with the addition of avibactam (p < 0.01), and the susceptibility to C/T was improved compared to piperacillin/tazobactam (p < 0.05) These data provide in vitro evidence that I-R may not be any more effective than imipenem monotherapy against MDR CFPA. The pattern of susceptibility observed for CZA and C/T in the current study was similar to data previously reported for non-CF-associated MDR P. aeruginosa. Nature Publishing Group UK 2022-10-07 /pmc/articles/PMC9547053/ /pubmed/36207358 http://dx.doi.org/10.1038/s41598-022-21101-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Haines, Robbie R.
Putsathit, Papanin
Hammer, Katherine A.
Tai, Anna S.
Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa
title Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa
title_full Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa
title_fullStr Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa
title_full_unstemmed Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa
title_short Activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant Pseudomonas aeruginosa
title_sort activity of newest generation β-lactam/β-lactamase inhibitor combination therapies against multidrug resistant pseudomonas aeruginosa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9547053/
https://www.ncbi.nlm.nih.gov/pubmed/36207358
http://dx.doi.org/10.1038/s41598-022-21101-x
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