Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections

Metallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to overcome. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new β-l...

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Autores principales:	Gianluca Morroni, Raffaela Bressan, Simona Fioriti, Gloria D’Achille, Marina Mingoia, Oscar Cirioni, Stefano Di Bella, Aurora Piazza, Francesco Comandatore, Carola Mauri, Roberta Migliavacca, Francesco Luzzaro, Luigi Principe, Cristina Lagatolla
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	aztreonam β-lactamases inhibitors synergism MBLs ESBL complicated infection Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/ac65774b77aa47749d9335f98c9d10de
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spelling	oai:doaj.org-article:ac65774b77aa47749d9335f98c9d10de2021-11-25T16:23:11ZAntimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections10.3390/antibiotics101113412079-6382https://doaj.org/article/ac65774b77aa47749d9335f98c9d10de2021-11-01T00:00:00Zhttps://www.mdpi.com/2079-6382/10/11/1341https://doaj.org/toc/2079-6382Metallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to overcome. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new β-lactamases inhibitors (BLIs) against MBL and ESBL co-producing Gram-negative clinical isolates. Six <i>Enterobacterales</i> and three non-fermenting bacilli co-producing MBL and ESBL determinants were selected as difficult-to-treat pathogens. ESBLs and MBLs genes were characterized by PCR and sequencing. The activity of ATM in combination with seven different BLIs (clavulanate, sulbactam, tazobactam, vaborbactam, avibactam, relebactam, zidebactam) was assessed by microdilution assay and time–kill curve. ATM plus avibactam was the most effective combination, able to restore ATM susceptibility in four out of nine tested isolates, reaching in some cases a 128-fold reduction of the MIC of ATM. In addition, relebactam and zidebactam showed to be effective, but with lesser reduction of the MIC of ATM. <i>E. meningoseptica</i> and <i>C. indologenes</i> were not inhibited by any ATM–BLI combination. ATM–BLI combinations demonstrated to be promising against MBL and ESBL co-producers, hence providing multiple options for treatment of related infections. However, no effective combination was found for some non-fermentative bacilli, suggesting the presence of additional resistance mechanisms that complicate the choice of an active therapy.Gianluca MorroniRaffaela BressanSimona FioritiGloria D’AchilleMarina MingoiaOscar CirioniStefano Di BellaAurora PiazzaFrancesco ComandatoreCarola MauriRoberta MigliavaccaFrancesco LuzzaroLuigi PrincipeCristina LagatollaMDPI AGarticleaztreonamβ-lactamases inhibitorssynergismMBLsESBLcomplicated infectionTherapeutics. PharmacologyRM1-950ENAntibiotics, Vol 10, Iss 1341, p 1341 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aztreonam β-lactamases inhibitors synergism MBLs ESBL complicated infection Therapeutics. Pharmacology RM1-950
spellingShingle	aztreonam β-lactamases inhibitors synergism MBLs ESBL complicated infection Therapeutics. Pharmacology RM1-950 Gianluca Morroni Raffaela Bressan Simona Fioriti Gloria D’Achille Marina Mingoia Oscar Cirioni Stefano Di Bella Aurora Piazza Francesco Comandatore Carola Mauri Roberta Migliavacca Francesco Luzzaro Luigi Principe Cristina Lagatolla Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections
description	Metallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to overcome. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new β-lactamases inhibitors (BLIs) against MBL and ESBL co-producing Gram-negative clinical isolates. Six <i>Enterobacterales</i> and three non-fermenting bacilli co-producing MBL and ESBL determinants were selected as difficult-to-treat pathogens. ESBLs and MBLs genes were characterized by PCR and sequencing. The activity of ATM in combination with seven different BLIs (clavulanate, sulbactam, tazobactam, vaborbactam, avibactam, relebactam, zidebactam) was assessed by microdilution assay and time–kill curve. ATM plus avibactam was the most effective combination, able to restore ATM susceptibility in four out of nine tested isolates, reaching in some cases a 128-fold reduction of the MIC of ATM. In addition, relebactam and zidebactam showed to be effective, but with lesser reduction of the MIC of ATM. <i>E. meningoseptica</i> and <i>C. indologenes</i> were not inhibited by any ATM–BLI combination. ATM–BLI combinations demonstrated to be promising against MBL and ESBL co-producers, hence providing multiple options for treatment of related infections. However, no effective combination was found for some non-fermentative bacilli, suggesting the presence of additional resistance mechanisms that complicate the choice of an active therapy.
format	article
author	Gianluca Morroni Raffaela Bressan Simona Fioriti Gloria D’Achille Marina Mingoia Oscar Cirioni Stefano Di Bella Aurora Piazza Francesco Comandatore Carola Mauri Roberta Migliavacca Francesco Luzzaro Luigi Principe Cristina Lagatolla
author_facet	Gianluca Morroni Raffaela Bressan Simona Fioriti Gloria D’Achille Marina Mingoia Oscar Cirioni Stefano Di Bella Aurora Piazza Francesco Comandatore Carola Mauri Roberta Migliavacca Francesco Luzzaro Luigi Principe Cristina Lagatolla
author_sort	Gianluca Morroni
title	Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections
title_short	Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections
title_full	Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections
title_fullStr	Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections
title_full_unstemmed	Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections
title_sort	antimicrobial activity of aztreonam in combination with old and new β-lactamase inhibitors against mbl and esbl co-producing gram-negative clinical isolates: possible options for the treatment of complicated infections
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ac65774b77aa47749d9335f98c9d10de
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Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections

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