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dc.contributor.author | Blanco-Martín, Tania | |
dc.contributor.author | Alonso-García, Isaac | |
dc.contributor.author | González-Pinto, Lucía | |
dc.contributor.author | Outeda-García, Michelle | |
dc.contributor.author | Guijarro-Sánchez, Paula | |
dc.contributor.author | López-Hernández, Inmaculada | |
dc.contributor.author | Perez-Vazquez, Maria | |
dc.contributor.author | Aracil, Belen | |
dc.contributor.author | López-Cerero, Lorena | |
dc.contributor.author | Fraile-Ribot, Pablo | |
dc.contributor.author | Oliver, Antonio | |
dc.contributor.author | Vázquez-Ucha, Juan Carlos | |
dc.contributor.author | Beceiro, Alejandro | |
dc.contributor.author | Bou, Germán | |
dc.contributor.author | Arca-Suárez, Jorge | |
dc.contributor.author | GEMARA/SEIMC-CIBERINFEC Study Group on the activity and resistance mechanisms to new β-lactams and β-lactamase inhibitors (PROTECT) | |
dc.date.accessioned | 2024-07-02T11:55:36Z | |
dc.date.available | 2024-07-02T11:55:36Z | |
dc.date.issued | 2024-05 | |
dc.identifier.citation | Int J Antimicrob Agents. 2024 May;63(5):107150. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19906 | |
dc.description.abstract | Objectives: To analyse the impact of the most clinically relevant β-lactamases and their interplay with low outer membrane permeability on the activity of cefiderocol, ceftazidime/avibactam, aztreonam/avibactam, cefepime/enmetazobactam, cefepime/taniborbactam, cefepime/zidebactam, imipenem/relebactam, meropenem/vaborbactam, meropenem/xeruborbactam and meropenem/nacubactam against recombinant Escherichia coli strains. Methods: We constructed 82 E. coli laboratory transformants expressing the main β-lactamases circulating in Enterobacterales (70 expressing single β-lactamase and 12 producing double carbapenemase) under high (E. coli TG1) and low (E. coli HB4) permeability conditions. Antimicrobial susceptibility testing was determined by reference broth microdilution. Results: Aztreonam/avibactam, cefepime/zidebactam, cefiderocol, meropenem/xeruborbactam and meropenem/nacubactam were active against all E. coli TG1 transformants. Imipenem/relebactam, meropenem/vaborbactam, cefepime/taniborbactam and cefepime/enmetazobactam were also highly active, but unstable against most of MBL-producing transformants. Combination of β-lactamases with porin deficiency (E. coli HB4) did not significantly affect the activity of aztreonam/avibactam, cefepime/zidebactam, cefiderocol or meropenem/nacubactam, but limited the effectiveness of the rest of carbapenem- and cefepime-based combinations. Double-carbapenemase production resulted in the loss of activity of most of the compounds tested, an effect particularly evident for those E. coli HB4 transformants in which MBLs were present. Conclusions: Our findings highlight the promising activity that cefiderocol and new β-lactam/β-lactamase inhibitors have against recombinant E. coli strains expressing widespread β-lactamases, including when these are combined with low permeability or other enzymes. Aztreonam/avibactam, cefiderocol, cefepime/zidebactam and meropenem/nacubactam will help to mitigate to some extent the urgency of new compounds able to resist MBL action, although NDM enzymes represent a growing challenge against which drug development efforts are still needed. | es_ES |
dc.description.sponsorship | This work was supported by the Instituto de Salud Carlos III (ISCIII, projects PI22/01212, PI20/01212 and PI21/00704) and co-funded by the European Union. This work was also supported by Merck Sharp & Dohme (MSD) through the Investigator Initiated Studies Program. The research was also funded by Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC, CB21/13/00055, CB21/13/00099, CB21/13/00095 and CB21/13/00012), the Spanish Network of Research in Infectious Diseases (REIPI, N° RD16/0016/0004 and N° RD16/0016/0006), integrated in the National Plan for Scientific Research, Development and Technological Innovation 2013–2016 and funded by the ISCIII-General Subdirection of Assessment and Promotion of the Research-European Regional Development Fund (FEDER) “A way of making Europe.” The study was also funded by the Axencia Galega de Innovación (GAIN), Consellería de Innovación, Consellería de Emprego e Industria (IN607D2021/12 to A.B. and IN607A 2016/22 to G.B.). This research was also supported by Personalized and precision medicine grant from the Instituto de Salud Carlos III (MePRAM Project, PMP22/00092), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación. T.B.-M. was financially supported by the ISCIII project PI20/00686 and by the Rio Hortega program (ISCIII, CM23/00095). I.A.-G. was financially supported by the Rio Hortega program (ISCIII, CM21/00076) and by the Juan Rodés program (ISCIII, JR23/00036). L.G.-P. was financially supported by the ISCIII project PI21/00704 and by the PFIS program (ISCIII, FI23/00074). J.C.V.-U. was financially supported by the Xunta de Galicia (IN606B-2022/009). J.A.-S. was financially supported by the Juan Rodés program (ISCIII, JR21/00026). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | β-lactamases | es_ES |
dc.subject | Cefiderocol | es_ES |
dc.subject | β-lactam/β-lactamase inhibitor | es_ES |
dc.subject | Combinations | es_ES |
dc.subject | Permeability | es_ES |
dc.subject | Double-carbapenemase | es_ES |
dc.subject | Escherichia coli | es_ES |
dc.subject.mesh | Escherichia coli | es_ES |
dc.subject.mesh | beta-Lactamases | es_ES |
dc.subject.mesh | Cephalosporins | es_ES |
dc.subject.mesh | Microbial Sensitivity Tests | es_ES |
dc.subject.mesh | beta-Lactamase Inhibitors | es_ES |
dc.subject.mesh | Azabicyclo Compounds | es_ES |
dc.subject.mesh | Anti-Bacterial Agents | es_ES |
dc.subject.mesh | Drug Combinations | es_ES |
dc.subject.mesh | Cyclooctanes | es_ES |
dc.subject.mesh | Cefiderocol | es_ES |
dc.subject.mesh | Ceftazidime | es_ES |
dc.subject.mesh | Cefepime | es_ES |
dc.subject.mesh | Borinic Acids | es_ES |
dc.subject.mesh | Carboxylic Acids | es_ES |
dc.subject.mesh | Lactams | es_ES |
dc.subject.mesh | Triazoles | es_ES |
dc.subject.mesh | Boronic Acids | es_ES |
dc.subject.mesh | Meropenem | es_ES |
dc.subject.mesh | Aztreonam | es_ES |
dc.subject.mesh | Imipenem | es_ES |
dc.subject.mesh | Bacterial Proteins | es_ES |
dc.subject.mesh | Heterocyclic Compounds, 1-Ring | es_ES |
dc.subject.mesh | Cell Membrane Permeability | es_ES |
dc.title | Activity of cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations against isogenic strains of Escherichia coli expressing single and double β-lactamases under high and low permeability conditions | es_ES |
dc.type | research article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 38513748 | es_ES |
dc.format.volume | 63 | es_ES |
dc.format.number | 5 | es_ES |
dc.format.page | 107150 | es_ES |
dc.identifier.doi | 10.1016/j.ijantimicag.2024.107150 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.contributor.funder | Merck, Sharp & Dohme | es_ES |
dc.contributor.funder | Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas) | es_ES |
dc.contributor.funder | RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España) | es_ES |
dc.contributor.funder | Plan Nacional de I+D+i (España) | es_ES |
dc.contributor.funder | Xunta de Galicia (España) | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1872-7913 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.ijantimicag.2024.107150 | es_ES |
dc.identifier.journal | International journal of antimicrobial agents | es_ES |
dc.repisalud.centro | ISCIII::Centro Nacional de Microbiología | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/MINECO//RD16%2F0016%2F0004/ES/RED ESPAÑOLA DE INVESTIGACIÓN EN PATOLOGÍAS INFECCIOSAS/ | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/MINECO//RD16%2F0016%2F0006/ES/RED ESPAÑOLA DE INVESTIGACIÓN EN PATOLOGÍAS INFECCIOSAS/ | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica, Técnica y de Innovación 2021-2023/PI22%2F01212/ES/Inhibidores de carbapenemasas: actividad frente a Enterobacterales productores de carbapenemasas, mecanismos e impacto en la evolución de la resistencia antimicrobiana (PROTECT)/ | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F01212/ES/DESARROLLO Y EVALUACION DE NUEVAS MOLECULAS ANTIMICROBIANAS DIRIGIDAS A PATOGENOS MULTIRRESISTENTES (INHIBIDORES DE ß-LACTAMASAS Y CONJUGADOS TETRACICLINAS-SIDEROFOROS). ESTUDIO NACIONAL ACINETOBACTER SPP./ | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI21%2F00704/ES/VACUNAS AUXOTROFAS ORALES PARA LA ERRADICACION DE BACTERIAS INTESTINALES: COLONIZACIÓN INTESTINAL POR KLEBSIELLA PNEUMONIAE MULTIRRESISTENTE COMO MODELO/ | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI20%2F00686/ES/DETECCION RAPIDA DE RESISTENCIAS ANTIBIOTICAS MEDIANTE ESPECTROMETRIA DE MASAS MALDI-TOF/ | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/CB21/13/00055 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/CB21/13/00099 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/CB21/13/00095 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/CB21/13/00012 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/PMP22/00092 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/CM23/00095 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/CM21/00076 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/JR23/00036 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/FI23/00074 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/JR21/00026 | es_ES |