Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study

Background: Pseudomonas aeruginosa shows resistance to several antibiotics and often develops such resistance during patient treatment. Objective: Develop an in vitro model, using clinical isolates of P. aeruginosa, to compare the ability of the imipenem and imipenem/relebactam to generate resistant...

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Autores: Ventero, Maria Paz, DE HARO, JOSE MANUEL, Molina-Pardines, Carmen, Sánchez Bautista, Antonia, García Rivera, Celia, Boix, Vicente, Merino de Lucas, Esperanza, López-Pérez, Mario, RODRIGUEZ DIAZ, JUAN CARLOS
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Miguel Hernández de Elche
Repositorio:REDIUMH. Depósito Digital de la UMH
OAI Identifier:oai:dspace.umh.es:11000/35462
Acceso en línea:https://hdl.handle.net/11000/35462
Access Level:acceso abierto
Palabra clave:Relebactam
Pseudomonas aeruginosa
Antibiotic resistance
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spelling Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro StudyVentero, Maria PazDE HARO, JOSE MANUELMolina-Pardines, CarmenSánchez Bautista, AntoniaGarcía Rivera, CeliaBoix, VicenteMerino de Lucas, EsperanzaLópez-Pérez, MarioRODRIGUEZ DIAZ, JUAN CARLOSRelebactamPseudomonas aeruginosaAntibiotic resistanceBackground: Pseudomonas aeruginosa shows resistance to several antibiotics and often develops such resistance during patient treatment. Objective: Develop an in vitro model, using clinical isolates of P. aeruginosa, to compare the ability of the imipenem and imipenem/relebactam to generate resistant mutants to imipenem and to other antibiotics. Perform a genotypic analysis to detect how the selective pressure changes their genomes. Methods: The antibiotics resistance was studied by microdilution assays and e-test, and the genotypic study was performed by NGS. Results: The isolates acquired resistance to imipenem in an average of 6 days, and to imipenem/relebactam in 12 days (p value = 0.004). After 30 days of exposure, 75% of the isolates reached a MIC > 64 mg/L for imipenem and 37.5% for imipenem/relebactam (p value = 0.077). The 37.5% and the 12.5% imipenem/relebactam mutants developed resistance to piperacillin/tazobactam and ceftazidime, respectively, while the 87.5% and 37.5% of the imipenem mutants showed resistance to these drugs (p value = 0.003, p value = 0.015). The main biological processes altered by the SNPs were the glycosylation pathway, transcriptional regulation, histidine kinase response, porins, and efflux pumps. Discussion: The addition of relebactam delays the generation of resistance to imipenem and limits the cross-resistance to other beta-lactams. The clinical relevance of this phenomenon, which has the limitation that it has been performed in vitro, should be evaluated by stewardship programs in clinical practice, as it could be useful in controlling multi-drug resistance in P. aeruginosaMDPIDepartamentos de la UMH::Producción Vegetal y Microbiología202520252023info:eu-repo/semantics/articleapplication/pdf12application/pdfhttps://hdl.handle.net/11000/35462reponame:REDIUMH. Depósito Digital de la UMHinstname:Universidad Miguel Hernández de ElcheIngléshttps://doi.org/10.3390/ antibiotics12111619info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:dspace.umh.es:11000/354622026-05-27T13:36:21Z
dc.title.none.fl_str_mv Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study
title Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study
spellingShingle Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study
Ventero, Maria Paz
Relebactam
Pseudomonas aeruginosa
Antibiotic resistance
title_short Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study
title_full Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study
title_fullStr Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study
title_full_unstemmed Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study
title_sort Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study
dc.creator.none.fl_str_mv Ventero, Maria Paz
DE HARO, JOSE MANUEL
Molina-Pardines, Carmen
Sánchez Bautista, Antonia
García Rivera, Celia
Boix, Vicente
Merino de Lucas, Esperanza
López-Pérez, Mario
RODRIGUEZ DIAZ, JUAN CARLOS
author Ventero, Maria Paz
author_facet Ventero, Maria Paz
DE HARO, JOSE MANUEL
Molina-Pardines, Carmen
Sánchez Bautista, Antonia
García Rivera, Celia
Boix, Vicente
Merino de Lucas, Esperanza
López-Pérez, Mario
RODRIGUEZ DIAZ, JUAN CARLOS
author_role author
author2 DE HARO, JOSE MANUEL
Molina-Pardines, Carmen
Sánchez Bautista, Antonia
García Rivera, Celia
Boix, Vicente
Merino de Lucas, Esperanza
López-Pérez, Mario
RODRIGUEZ DIAZ, JUAN CARLOS
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Departamentos de la UMH::Producción Vegetal y Microbiología
dc.subject.none.fl_str_mv Relebactam
Pseudomonas aeruginosa
Antibiotic resistance
topic Relebactam
Pseudomonas aeruginosa
Antibiotic resistance
description Background: Pseudomonas aeruginosa shows resistance to several antibiotics and often develops such resistance during patient treatment. Objective: Develop an in vitro model, using clinical isolates of P. aeruginosa, to compare the ability of the imipenem and imipenem/relebactam to generate resistant mutants to imipenem and to other antibiotics. Perform a genotypic analysis to detect how the selective pressure changes their genomes. Methods: The antibiotics resistance was studied by microdilution assays and e-test, and the genotypic study was performed by NGS. Results: The isolates acquired resistance to imipenem in an average of 6 days, and to imipenem/relebactam in 12 days (p value = 0.004). After 30 days of exposure, 75% of the isolates reached a MIC > 64 mg/L for imipenem and 37.5% for imipenem/relebactam (p value = 0.077). The 37.5% and the 12.5% imipenem/relebactam mutants developed resistance to piperacillin/tazobactam and ceftazidime, respectively, while the 87.5% and 37.5% of the imipenem mutants showed resistance to these drugs (p value = 0.003, p value = 0.015). The main biological processes altered by the SNPs were the glycosylation pathway, transcriptional regulation, histidine kinase response, porins, and efflux pumps. Discussion: The addition of relebactam delays the generation of resistance to imipenem and limits the cross-resistance to other beta-lactams. The clinical relevance of this phenomenon, which has the limitation that it has been performed in vitro, should be evaluated by stewardship programs in clinical practice, as it could be useful in controlling multi-drug resistance in P. aeruginosa
publishDate 2023
dc.date.none.fl_str_mv 2023
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/11000/35462
url https://hdl.handle.net/11000/35462
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3390/ antibiotics12111619
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.format.none.fl_str_mv application/pdf
12
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:REDIUMH. Depósito Digital de la UMH
instname:Universidad Miguel Hernández de Elche
instname_str Universidad Miguel Hernández de Elche
reponame_str REDIUMH. Depósito Digital de la UMH
collection REDIUMH. Depósito Digital de la UMH
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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