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New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams

Carbapenem resistance is a major global health problem that seriously compromises the treatment of infections caused by nosocomial pathogens. Resistance to carbapenems mainly occurs via the production of carbapenemases, such as VIM, IMP, NDM, KPC and OXA, among others. Preclinical and clinical trial...

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Detalles Bibliográficos
Autores principales: Vázquez-Ucha, Juan C., Arca-Suárez, Jorge, Bou, Germán, Beceiro, Alejandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731173/
https://www.ncbi.nlm.nih.gov/pubmed/33291334
http://dx.doi.org/10.3390/ijms21239308
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author Vázquez-Ucha, Juan C.
Arca-Suárez, Jorge
Bou, Germán
Beceiro, Alejandro
author_facet Vázquez-Ucha, Juan C.
Arca-Suárez, Jorge
Bou, Germán
Beceiro, Alejandro
author_sort Vázquez-Ucha, Juan C.
collection PubMed
description Carbapenem resistance is a major global health problem that seriously compromises the treatment of infections caused by nosocomial pathogens. Resistance to carbapenems mainly occurs via the production of carbapenemases, such as VIM, IMP, NDM, KPC and OXA, among others. Preclinical and clinical trials are currently underway to test a new generation of promising inhibitors, together with the recently approved avibactam, relebactam and vaborbactam. This review summarizes the main, most promising carbapenemase inhibitors synthesized to date, as well as their spectrum of activity and current stage of development. We particularly focus on β-lactam/β-lactamase inhibitor combinations that could potentially be used to treat infections caused by carbapenemase-producer pathogens of critical priority. The emergence of these new combinations represents a step forward in the fight against antimicrobial resistance, especially in regard to metallo-β-lactamases and carbapenem-hydrolysing class D β-lactamases, not currently inhibited by any clinically approved inhibitor.
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spelling pubmed-77311732020-12-12 New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams Vázquez-Ucha, Juan C. Arca-Suárez, Jorge Bou, Germán Beceiro, Alejandro Int J Mol Sci Review Carbapenem resistance is a major global health problem that seriously compromises the treatment of infections caused by nosocomial pathogens. Resistance to carbapenems mainly occurs via the production of carbapenemases, such as VIM, IMP, NDM, KPC and OXA, among others. Preclinical and clinical trials are currently underway to test a new generation of promising inhibitors, together with the recently approved avibactam, relebactam and vaborbactam. This review summarizes the main, most promising carbapenemase inhibitors synthesized to date, as well as their spectrum of activity and current stage of development. We particularly focus on β-lactam/β-lactamase inhibitor combinations that could potentially be used to treat infections caused by carbapenemase-producer pathogens of critical priority. The emergence of these new combinations represents a step forward in the fight against antimicrobial resistance, especially in regard to metallo-β-lactamases and carbapenem-hydrolysing class D β-lactamases, not currently inhibited by any clinically approved inhibitor. MDPI 2020-12-06 /pmc/articles/PMC7731173/ /pubmed/33291334 http://dx.doi.org/10.3390/ijms21239308 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Vázquez-Ucha, Juan C.
Arca-Suárez, Jorge
Bou, Germán
Beceiro, Alejandro
New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams
title New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams
title_full New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams
title_fullStr New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams
title_full_unstemmed New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams
title_short New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams
title_sort new carbapenemase inhibitors: clearing the way for the β-lactams
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731173/
https://www.ncbi.nlm.nih.gov/pubmed/33291334
http://dx.doi.org/10.3390/ijms21239308
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