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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doaj-2981b89190cf4a4f8b2a1a5a192d72b02020-12-07T00:02:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-01219308930810.3390/ijms21239308New Carbapenemase Inhibitors: Clearing the Way for the β-LactamsJuan C. Vázquez-Ucha0Jorge Arca-Suárez1Germán Bou2Alejandro Beceiro3Servicio de Microbiología, Instituto de Investigación Biomédica de A Coruña (INIBIC-CICA), Complejo Hospitalario Universitario A Coruña (CHUAC), As Xubias 84, 15006 A Coruña, SpainServicio de Microbiología, Instituto de Investigación Biomédica de A Coruña (INIBIC-CICA), Complejo Hospitalario Universitario A Coruña (CHUAC), As Xubias 84, 15006 A Coruña, SpainServicio de Microbiología, Instituto de Investigación Biomédica de A Coruña (INIBIC-CICA), Complejo Hospitalario Universitario A Coruña (CHUAC), As Xubias 84, 15006 A Coruña, SpainServicio de Microbiología, Instituto de Investigación Biomédica de A Coruña (INIBIC-CICA), Complejo Hospitalario Universitario A Coruña (CHUAC), As Xubias 84, 15006 A Coruña, SpainCarbapenem 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.https://www.mdpi.com/1422-0067/21/23/9308carbapenemaseinhibitorantibiotic resistancecarbapenem resistancemetallo-β-lactamasesserine-β-lactamases |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Juan C. Vázquez-Ucha Jorge Arca-Suárez Germán Bou Alejandro Beceiro |
spellingShingle |
Juan C. Vázquez-Ucha Jorge Arca-Suárez Germán Bou Alejandro Beceiro New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams International Journal of Molecular Sciences carbapenemase inhibitor antibiotic resistance carbapenem resistance metallo-β-lactamases serine-β-lactamases |
author_facet |
Juan C. Vázquez-Ucha Jorge Arca-Suárez Germán Bou Alejandro Beceiro |
author_sort |
Juan C. Vázquez-Ucha |
title |
New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams |
title_short |
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_sort |
new carbapenemase inhibitors: clearing the way for the β-lactams |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-12-01 |
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. |
topic |
carbapenemase inhibitor antibiotic resistance carbapenem resistance metallo-β-lactamases serine-β-lactamases |
url |
https://www.mdpi.com/1422-0067/21/23/9308 |
work_keys_str_mv |
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1724398141048881152 |