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Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing

Multidrug resistance (MDR) represents a serious global threat due to the rapid global spread and limited antimicrobial options for treatment of difficult-to-treat (DTR) infections sustained by MDR pathogens. Recently, novel β-lactams/β-lactamase inhibitor combinations (βL-βLICs) have been developed...

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Autores principales: Gaibani, Paolo, Giani, Tommaso, Bovo, Federica, Lombardo, Donatella, Amadesi, Stefano, Lazzarotto, Tiziana, Coppi, Marco, Rossolini, Gian Maria, Ambretti, Simone
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137602/
https://www.ncbi.nlm.nih.gov/pubmed/35625273
http://dx.doi.org/10.3390/antibiotics11050628
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author Gaibani, Paolo
Giani, Tommaso
Bovo, Federica
Lombardo, Donatella
Amadesi, Stefano
Lazzarotto, Tiziana
Coppi, Marco
Rossolini, Gian Maria
Ambretti, Simone
author_facet Gaibani, Paolo
Giani, Tommaso
Bovo, Federica
Lombardo, Donatella
Amadesi, Stefano
Lazzarotto, Tiziana
Coppi, Marco
Rossolini, Gian Maria
Ambretti, Simone
author_sort Gaibani, Paolo
collection PubMed
description Multidrug resistance (MDR) represents a serious global threat due to the rapid global spread and limited antimicrobial options for treatment of difficult-to-treat (DTR) infections sustained by MDR pathogens. Recently, novel β-lactams/β-lactamase inhibitor combinations (βL-βLICs) have been developed for the treatment of DTR infections due to MDR Gram-negative pathogens. Although novel βL-βLICs exhibited promising in vitro and in vivo activities against MDR pathogens, emerging resistances to these novel molecules have recently been reported. Resistance to novel βL-βLICs is due to several mechanisms including porin deficiencies, increasing carbapenemase expression and/or enzyme mutations. In this review, we summarized the main mechanisms related to the resistance to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam in MDR Gram-negative micro-organisms. We focused on antimicrobial activities and resistance traits with particular regard to molecular mechanisms related to resistance to novel βL-βLICs. Lastly, we described and discussed the main detection methods for antimicrobial susceptibility testing of such molecules. With increasing reports of resistance to novel βL-βLICs, continuous attention should be maintained on the monitoring of the phenotypic traits of MDR pathogens, into the characterization of related mechanisms, and on the emergence of cross-resistance to these novel antimicrobials.
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spelling pubmed-91376022022-05-28 Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing Gaibani, Paolo Giani, Tommaso Bovo, Federica Lombardo, Donatella Amadesi, Stefano Lazzarotto, Tiziana Coppi, Marco Rossolini, Gian Maria Ambretti, Simone Antibiotics (Basel) Review Multidrug resistance (MDR) represents a serious global threat due to the rapid global spread and limited antimicrobial options for treatment of difficult-to-treat (DTR) infections sustained by MDR pathogens. Recently, novel β-lactams/β-lactamase inhibitor combinations (βL-βLICs) have been developed for the treatment of DTR infections due to MDR Gram-negative pathogens. Although novel βL-βLICs exhibited promising in vitro and in vivo activities against MDR pathogens, emerging resistances to these novel molecules have recently been reported. Resistance to novel βL-βLICs is due to several mechanisms including porin deficiencies, increasing carbapenemase expression and/or enzyme mutations. In this review, we summarized the main mechanisms related to the resistance to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam in MDR Gram-negative micro-organisms. We focused on antimicrobial activities and resistance traits with particular regard to molecular mechanisms related to resistance to novel βL-βLICs. Lastly, we described and discussed the main detection methods for antimicrobial susceptibility testing of such molecules. With increasing reports of resistance to novel βL-βLICs, continuous attention should be maintained on the monitoring of the phenotypic traits of MDR pathogens, into the characterization of related mechanisms, and on the emergence of cross-resistance to these novel antimicrobials. MDPI 2022-05-06 /pmc/articles/PMC9137602/ /pubmed/35625273 http://dx.doi.org/10.3390/antibiotics11050628 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Gaibani, Paolo
Giani, Tommaso
Bovo, Federica
Lombardo, Donatella
Amadesi, Stefano
Lazzarotto, Tiziana
Coppi, Marco
Rossolini, Gian Maria
Ambretti, Simone
Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing
title Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing
title_full Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing
title_fullStr Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing
title_full_unstemmed Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing
title_short Resistance to Ceftazidime/Avibactam, Meropenem/Vaborbactam and Imipenem/Relebactam in Gram-Negative MDR Bacilli: Molecular Mechanisms and Susceptibility Testing
title_sort resistance to ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam in gram-negative mdr bacilli: molecular mechanisms and susceptibility testing
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137602/
https://www.ncbi.nlm.nih.gov/pubmed/35625273
http://dx.doi.org/10.3390/antibiotics11050628
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