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

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/relebacta...

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Autores: Blanco Martín, Tania, Alonso García, Isaac, González Pinto, Lucía, Outeda García, Michelle, Guijarro Sánchez, Paula, López Hernández, Inmaculada, Pérez Vázquez, María, Aracil, Belén, López Cerero, Lorena, Fraile Ribot, Pablo, Arca Suárez, Jorge
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/165841
Acceso en línea:https://hdl.handle.net/11441/165841
https://doi.org/10.1016/j.ijantimicag.2024.107150
Access Level:acceso abierto
Palabra clave:Cefiderocol
Double-carbapenemase
Escherichia coli
Permeability
β-lactam/β-lactamase inhibitor combinations
β-lactamases
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oai_identifier_str oai:idus.us.es:11441/165841
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv 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
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
spellingShingle 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
Blanco Martín, Tania
Cefiderocol
Double-carbapenemase
Escherichia coli
Permeability
β-lactam/β-lactamase inhibitor combinations
β-lactamases
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
dc.creator.none.fl_str_mv Blanco Martín, Tania
Alonso García, Isaac
González Pinto, Lucía
Outeda García, Michelle
Guijarro Sánchez, Paula
López Hernández, Inmaculada
Pérez Vázquez, María
Aracil, Belén
López Cerero, Lorena
Fraile Ribot, Pablo
Arca Suárez, Jorge
author Blanco Martín, Tania
author_facet Blanco Martín, Tania
Alonso García, Isaac
González Pinto, Lucía
Outeda García, Michelle
Guijarro Sánchez, Paula
López Hernández, Inmaculada
Pérez Vázquez, María
Aracil, Belén
López Cerero, Lorena
Fraile Ribot, Pablo
Arca Suárez, Jorge
author_role author
author2 Alonso García, Isaac
González Pinto, Lucía
Outeda García, Michelle
Guijarro Sánchez, Paula
López Hernández, Inmaculada
Pérez Vázquez, María
Aracil, Belén
López Cerero, Lorena
Fraile Ribot, Pablo
Arca Suárez, Jorge
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Microbiología
Instituto de Salud Carlos III
Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)
Red de Investigación en Enfermedades Infecciosas (REIPI)
Xunta de Galicia
dc.subject.none.fl_str_mv Cefiderocol
Double-carbapenemase
Escherichia coli
Permeability
β-lactam/β-lactamase inhibitor combinations
β-lactamases
topic Cefiderocol
Double-carbapenemase
Escherichia coli
Permeability
β-lactam/β-lactamase inhibitor combinations
β-lactamases
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2024
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://hdl.handle.net/11441/165841
https://doi.org/10.1016/j.ijantimicag.2024.107150
url https://hdl.handle.net/11441/165841
https://doi.org/10.1016/j.ijantimicag.2024.107150
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv International Journal of Antimicrobial Agents, 63 (5), 107150.
Blanco Martín, T., Alonso García, I., González Pinto, L., Outeda García, M., Guijarro Sánchez, P., López Hernández, I.,...,Arca Suárez, J. (2024). Corrigendum to “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” [International Journal of Antimicrobial Agents Volume 63, Issue 5 (2024) 107150]. International Journal of Antimicrobial Agents, 64 (2), 107264. https://doi.org/10.1016/j.ijantimicag.2024.107264.
https://hdl.handle.net/11441/171311
PI22/01212
PI20/01212
PI21/00704
PMP22/00092
CM23/00095
CM21/00076
JR23/00036
PI21/00704
FI23/00074
JR21/00026
CB21/13/00055
CB21/13/00099
CB21/13/00095
CB21/13/00012
RD16/0016/0004
RD16/0016/0006
IN607D2021/12
IN607A 2016/22
IN606B-2022/009
https://doi.org/10.1016/j.ijantimicag.2024.107150
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419636932476928
spelling 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 ConditionsBlanco Martín, TaniaAlonso García, IsaacGonzález Pinto, LucíaOuteda García, MichelleGuijarro Sánchez, PaulaLópez Hernández, InmaculadaPérez Vázquez, MaríaAracil, BelénLópez Cerero, LorenaFraile Ribot, PabloArca Suárez, JorgeCefiderocolDouble-carbapenemaseEscherichia coliPermeabilityβ-lactam/β-lactamase inhibitor combinationsβ-lactamasesObjectives: 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.Instituto de Salud Carlos III PI22/01212, PI20/01212, PI21/00704, PMP22/00092, CM23/00095, CM21/00076, JR23/00036, PI21/00704, FI23/00074, JR21/00026Centro de Investigación Biomédica en Red de Enfermedades Infecciosas CB21/13/00055, CB21/13/00099, CB21/13/00095, CB21/13/00012Red de Investigación en Enfermedades Infecciosas RD16/0016/0004, RD16/0016/0006Xunta de Galicia IN607D2021/12, IN607A 2016/22, IN606B-2022/009ElsevierMicrobiologíaInstituto de Salud Carlos IIICentro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)Red de Investigación en Enfermedades Infecciosas (REIPI)Xunta de Galicia2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/165841https://doi.org/10.1016/j.ijantimicag.2024.107150reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésInternational Journal of Antimicrobial Agents, 63 (5), 107150.Blanco Martín, T., Alonso García, I., González Pinto, L., Outeda García, M., Guijarro Sánchez, P., López Hernández, I.,...,Arca Suárez, J. (2024). Corrigendum to “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” [International Journal of Antimicrobial Agents Volume 63, Issue 5 (2024) 107150]. International Journal of Antimicrobial Agents, 64 (2), 107264. https://doi.org/10.1016/j.ijantimicag.2024.107264.https://hdl.handle.net/11441/171311PI22/01212PI20/01212PI21/00704PMP22/00092CM23/00095CM21/00076JR23/00036PI21/00704FI23/00074JR21/00026CB21/13/00055CB21/13/00099CB21/13/00095CB21/13/00012RD16/0016/0004RD16/0016/0006IN607D2021/12IN607A 2016/22IN606B-2022/009https://doi.org/10.1016/j.ijantimicag.2024.107150info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1658412026-06-17T12:51:07Z
score 15,811543

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