Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp

Autores
Wong, Olivia; Mezcord, Vyanka; Lopez, Christina; Traglia, German Matias; Pasteran, Fernando; Tuttobene, Marisel Romina; Corso, Alejandra; Tolmasky, Marcelo E.; Bonomo, Robert A.; Ramirez, María Soledad
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections.
Fil: Wong, Olivia. California State University; Estados Unidos
Fil: Mezcord, Vyanka. California State University; Estados Unidos
Fil: Lopez, Christina. California State University; Estados Unidos
Fil: Traglia, German Matias. Universidad de la República; Uruguay
Fil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Tuttobene, Marisel Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Corso, Alejandra. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Tolmasky, Marcelo E.. California State University; Estados Unidos
Fil: Bonomo, Robert A.. No especifíca;
Fil: Ramirez, María Soledad. California State University; Estados Unidos
Materia
ACINETOBACTER BAUMANNII
CEFIDEROCOL
AVIBACTAM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/266347
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/266347
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter sppWong, OliviaMezcord, VyankaLopez, ChristinaTraglia, German MatiasPasteran, FernandoTuttobene, Marisel RominaCorso, AlejandraTolmasky, Marcelo E.Bonomo, Robert A.Ramirez, María SoledadACINETOBACTER BAUMANNIICEFIDEROCOLAVIBACTAMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections.Fil: Wong, Olivia. California State University; Estados UnidosFil: Mezcord, Vyanka. California State University; Estados UnidosFil: Lopez, Christina. California State University; Estados UnidosFil: Traglia, German Matias. Universidad de la República; UruguayFil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Tuttobene, Marisel Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Corso, Alejandra. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Tolmasky, Marcelo E.. California State University; Estados UnidosFil: Bonomo, Robert A.. No especifíca;Fil: Ramirez, María Soledad. California State University; Estados UnidosAmerican Society for Microbiology2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266347Wong, Olivia; Mezcord, Vyanka; Lopez, Christina; Traglia, German Matias; Pasteran, Fernando; et al.; Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp; American Society for Microbiology; Microbiology Spectrum; 12; 10; 8-2024; 1-112165-0497CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/spectrum.00930-24info:eu-repo/semantics/altIdentifier/doi/10.1128/spectrum.00930-24info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:19Zoai:ri.conicet.gov.ar:11336/266347instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:47:19.886CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
title Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
spellingShingle Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
Wong, Olivia
ACINETOBACTER BAUMANNII
CEFIDEROCOL
AVIBACTAM
title_short Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
title_full Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
title_fullStr Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
title_full_unstemmed Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
title_sort Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp
dc.creator.none.fl_str_mv Wong, Olivia
Mezcord, Vyanka
Lopez, Christina
Traglia, German Matias
Pasteran, Fernando
Tuttobene, Marisel Romina
Corso, Alejandra
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramirez, María Soledad
author Wong, Olivia
author_facet Wong, Olivia
Mezcord, Vyanka
Lopez, Christina
Traglia, German Matias
Pasteran, Fernando
Tuttobene, Marisel Romina
Corso, Alejandra
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramirez, María Soledad
author_role author
author2 Mezcord, Vyanka
Lopez, Christina
Traglia, German Matias
Pasteran, Fernando
Tuttobene, Marisel Romina
Corso, Alejandra
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramirez, María Soledad
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACINETOBACTER BAUMANNII
CEFIDEROCOL
AVIBACTAM
topic ACINETOBACTER BAUMANNII
CEFIDEROCOL
AVIBACTAM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections.
Fil: Wong, Olivia. California State University; Estados Unidos
Fil: Mezcord, Vyanka. California State University; Estados Unidos
Fil: Lopez, Christina. California State University; Estados Unidos
Fil: Traglia, German Matias. Universidad de la República; Uruguay
Fil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Tuttobene, Marisel Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
Fil: Corso, Alejandra. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Tolmasky, Marcelo E.. California State University; Estados Unidos
Fil: Bonomo, Robert A.. No especifíca;
Fil: Ramirez, María Soledad. California State University; Estados Unidos
description Cefiderocol, a siderophore-cephalosporine conjugate antibiotic, shows promise as a therapeutic option for carbapenem-resistant (CR) Acinetobacter infections. While resistance has already been reported in A. baumannii, combination therapies with avibactam or sulbactam reduce MICs of cefiderocol, extending its efficacy. However, careful consideration is necessary when using these combinations. In our experiments, exposure of A. baumannii and A. lwoffii to cefiderocol and sulbactam or avibactam led to the selection of cefiderocol-resistant strains. Three of those were subjected to whole genome sequencing and transcriptomic analysis. The strains all possessed synonymous and non-synonymous substitutions and short deletions. The most significant mutations affected efflux pumps, transcriptional regulators, and iron homeostasis genes. Transcriptomics showed significant alterations in expression levels of outer membrane proteins, iron homeostasis, and β-lactamases, suggesting adaptive responses to selective pressure. This study underscores the importance of carefully assessing drug synergies, as they may inadvertently foster the selection of resistant variants and complicate the management of CR Acinetobacter infections.
publishDate 2024
dc.date.none.fl_str_mv 2024-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/266347
Wong, Olivia; Mezcord, Vyanka; Lopez, Christina; Traglia, German Matias; Pasteran, Fernando; et al.; Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp; American Society for Microbiology; Microbiology Spectrum; 12; 10; 8-2024; 1-11
2165-0497
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266347
identifier_str_mv Wong, Olivia; Mezcord, Vyanka; Lopez, Christina; Traglia, German Matias; Pasteran, Fernando; et al.; Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp; American Society for Microbiology; Microbiology Spectrum; 12; 10; 8-2024; 1-11
2165-0497
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/spectrum.00930-24
info:eu-repo/semantics/altIdentifier/doi/10.1128/spectrum.00930-24
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.069144

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