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 MP, Haro-Moreno JM, Molina-Pardines C, Sánchez-Bautista A, García-Rivera C, Boix V, Merino E, López-Pérez M, Rodríguez JC
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Recursos:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
Repositorio:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
OAI Identifier:oai:isabial.fundanetsuite.com:p9946
Acesso em linha:https://isabial.portalinvestigacion.com/publicaciones9946
https://www.mdpi.com/2079-6382/12/11/1619
Access Level:acceso abierto
Palavra-chave:Pseudomonas aeruginosa
antibiotic resistance
relebactam
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spelling Role of Relebactam in the Antibiotic Resistance Acquisition in Pseudomonas aeruginosa: In Vitro Study.Ventero MPHaro-Moreno JMMolina-Pardines CSánchez-Bautista AGarcía-Rivera CBoix VMerino ELópez-Pérez MRodríguez JCPseudomonas aeruginosaantibiotic resistancerelebactamBACKGROUND: 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.MDPI2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://isabial.portalinvestigacion.com/publicaciones9946https://www.mdpi.com/2079-6382/12/11/1619Antibiotics-BaselISSN: 20796382reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicanteinstname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)Inglésinfo:eu-repo/semantics/openAccessoai:isabial.fundanetsuite.com:p99462026-06-12T10:20:37Z
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 MP
Pseudomonas aeruginosa
antibiotic resistance
relebactam
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 MP
Haro-Moreno JM
Molina-Pardines C
Sánchez-Bautista A
García-Rivera C
Boix V
Merino E
López-Pérez M
Rodríguez JC
author Ventero MP
author_facet Ventero MP
Haro-Moreno JM
Molina-Pardines C
Sánchez-Bautista A
García-Rivera C
Boix V
Merino E
López-Pérez M
Rodríguez JC
author_role author
author2 Haro-Moreno JM
Molina-Pardines C
Sánchez-Bautista A
García-Rivera C
Boix V
Merino E
López-Pérez M
Rodríguez JC
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Pseudomonas aeruginosa
antibiotic resistance
relebactam
topic Pseudomonas aeruginosa
antibiotic resistance
relebactam
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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://isabial.portalinvestigacion.com/publicaciones9946
https://www.mdpi.com/2079-6382/12/11/1619
url https://isabial.portalinvestigacion.com/publicaciones9946
https://www.mdpi.com/2079-6382/12/11/1619
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Antibiotics-Basel
ISSN: 20796382
reponame:r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
instname:Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
instname_str Instituto de Investigación Biomédica y Sanitaria de Alicante (ISABIAL)
reponame_str r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
collection r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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