Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates

Autores
Cedano, Jose; Baez, Michelle; Pasteran, Fernando; Montaña, Sabrina Daiana; Ra, Grace; Fua, Venjaminne; Corso, Alejandra; Tolmasky, Marcelo E.; Bonomo, Robert A.; Ramírez, María Soledad
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially Acinetobacter baumannii. Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant A. baumannii (CRAB) isolates. In the present study, we tested zidebactam, a novel DBO with an additional mechanism of action, in combination with sulbactam against CRAB isolates, including strains that exhibited resistance against sulbactam/avibactam combination. A panel of 43 geographically and genetically distinct CRAB isolates recovered from different hospitals and containing different mechanisms of resistance were included in the present study. We also tested three reference strains (AB0057, AB5075, and AYE). Minimum inhibitory concentrations (MICs) for sulbactam (range 0.12–512 mg/l) and sulbactam plus 4 mg/l zidebactam were performed using microdilution according to CLSI Standards. A decrease ≥2 dilutions in sulbactam MICs was observed in 84% of the isolates when tested in combination with zidebactam. The sulbactam/zidebactam combination was able to restore sulbactam susceptibility in 91% of the isolates, including isolates that were resistant to sulbactam/avibactam combination. These data encouraged us to further explore sulbactam/zidebactam in other experimental models especially against CRAB isolates resistant to other DBOs.
Fil: Cedano, Jose. California State University; Estados Unidos
Fil: Baez, Michelle. California State University; Estados Unidos
Fil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Montaña, Sabrina Daiana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Ra, Grace. California State University; Estados Unidos
Fil: Fua, Venjaminne. California State University; Estados Unidos
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.. Case Western Reserve University School of Medicine; Estados Unidos
Fil: Ramírez, María Soledad. California State University; Estados Unidos
Materia
ACINETOBACTER
CARBAPENEM-RESISTANCE
DBOS
SULBACTAM
SUSCEPTIBILITY
SYNERGY
ZIDEBACTAM
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:11336/218051
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/218051
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolatesCedano, JoseBaez, MichellePasteran, FernandoMontaña, Sabrina DaianaRa, GraceFua, VenjaminneCorso, AlejandraTolmasky, Marcelo E.Bonomo, Robert A.Ramírez, María SoledadACINETOBACTERCARBAPENEM-RESISTANCEDBOSSULBACTAMSUSCEPTIBILITYSYNERGYZIDEBACTAMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially Acinetobacter baumannii. Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant A. baumannii (CRAB) isolates. In the present study, we tested zidebactam, a novel DBO with an additional mechanism of action, in combination with sulbactam against CRAB isolates, including strains that exhibited resistance against sulbactam/avibactam combination. A panel of 43 geographically and genetically distinct CRAB isolates recovered from different hospitals and containing different mechanisms of resistance were included in the present study. We also tested three reference strains (AB0057, AB5075, and AYE). Minimum inhibitory concentrations (MICs) for sulbactam (range 0.12–512 mg/l) and sulbactam plus 4 mg/l zidebactam were performed using microdilution according to CLSI Standards. A decrease ≥2 dilutions in sulbactam MICs was observed in 84% of the isolates when tested in combination with zidebactam. The sulbactam/zidebactam combination was able to restore sulbactam susceptibility in 91% of the isolates, including isolates that were resistant to sulbactam/avibactam combination. These data encouraged us to further explore sulbactam/zidebactam in other experimental models especially against CRAB isolates resistant to other DBOs.Fil: Cedano, Jose. California State University; Estados UnidosFil: Baez, Michelle. California State University; Estados UnidosFil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Montaña, Sabrina Daiana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ra, Grace. California State University; Estados UnidosFil: Fua, Venjaminne. California State University; Estados UnidosFil: 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.. Case Western Reserve University School of Medicine; Estados UnidosFil: Ramírez, María Soledad. California State University; Estados UnidosFrontiers Media2022-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/218051Cedano, Jose; Baez, Michelle; Pasteran, Fernando; Montaña, Sabrina Daiana; Ra, Grace; et al.; Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 12; 7-2022; 1-62235-2988CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2022.918868info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:54:25Zoai:ri.conicet.gov.ar:11336/218051instacron: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:34982025-09-03 09:54:26.511CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
spellingShingle Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
Cedano, Jose
ACINETOBACTER
CARBAPENEM-RESISTANCE
DBOS
SULBACTAM
SUSCEPTIBILITY
SYNERGY
ZIDEBACTAM
title_short Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title_full Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title_fullStr Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title_full_unstemmed Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
title_sort Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates
dc.creator.none.fl_str_mv Cedano, Jose
Baez, Michelle
Pasteran, Fernando
Montaña, Sabrina Daiana
Ra, Grace
Fua, Venjaminne
Corso, Alejandra
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
author Cedano, Jose
author_facet Cedano, Jose
Baez, Michelle
Pasteran, Fernando
Montaña, Sabrina Daiana
Ra, Grace
Fua, Venjaminne
Corso, Alejandra
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
author_role author
author2 Baez, Michelle
Pasteran, Fernando
Montaña, Sabrina Daiana
Ra, Grace
Fua, Venjaminne
Corso, Alejandra
Tolmasky, Marcelo E.
Bonomo, Robert A.
Ramírez, María Soledad
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACINETOBACTER
CARBAPENEM-RESISTANCE
DBOS
SULBACTAM
SUSCEPTIBILITY
SYNERGY
ZIDEBACTAM
topic ACINETOBACTER
CARBAPENEM-RESISTANCE
DBOS
SULBACTAM
SUSCEPTIBILITY
SYNERGY
ZIDEBACTAM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially Acinetobacter baumannii. Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant A. baumannii (CRAB) isolates. In the present study, we tested zidebactam, a novel DBO with an additional mechanism of action, in combination with sulbactam against CRAB isolates, including strains that exhibited resistance against sulbactam/avibactam combination. A panel of 43 geographically and genetically distinct CRAB isolates recovered from different hospitals and containing different mechanisms of resistance were included in the present study. We also tested three reference strains (AB0057, AB5075, and AYE). Minimum inhibitory concentrations (MICs) for sulbactam (range 0.12–512 mg/l) and sulbactam plus 4 mg/l zidebactam were performed using microdilution according to CLSI Standards. A decrease ≥2 dilutions in sulbactam MICs was observed in 84% of the isolates when tested in combination with zidebactam. The sulbactam/zidebactam combination was able to restore sulbactam susceptibility in 91% of the isolates, including isolates that were resistant to sulbactam/avibactam combination. These data encouraged us to further explore sulbactam/zidebactam in other experimental models especially against CRAB isolates resistant to other DBOs.
Fil: Cedano, Jose. California State University; Estados Unidos
Fil: Baez, Michelle. California State University; Estados Unidos
Fil: Pasteran, Fernando. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Fil: Montaña, Sabrina Daiana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Ra, Grace. California State University; Estados Unidos
Fil: Fua, Venjaminne. California State University; Estados Unidos
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.. Case Western Reserve University School of Medicine; Estados Unidos
Fil: Ramírez, María Soledad. California State University; Estados Unidos
description Carbapenems are commonly used to treat infections caused by multidrug-resistant (MDR) bacteria. Unfortunately, carbapenem resistance is increasingly reported in many gram-negative bacteria, especially Acinetobacter baumannii. Diazabicyclooctane (DBO) β-lactamase inhibitors, such as avibactam (AVI), when combined with sulbactam successfully restore sulbactam susceptibility against certain carbapenem-resistant A. baumannii (CRAB) isolates. In the present study, we tested zidebactam, a novel DBO with an additional mechanism of action, in combination with sulbactam against CRAB isolates, including strains that exhibited resistance against sulbactam/avibactam combination. A panel of 43 geographically and genetically distinct CRAB isolates recovered from different hospitals and containing different mechanisms of resistance were included in the present study. We also tested three reference strains (AB0057, AB5075, and AYE). Minimum inhibitory concentrations (MICs) for sulbactam (range 0.12–512 mg/l) and sulbactam plus 4 mg/l zidebactam were performed using microdilution according to CLSI Standards. A decrease ≥2 dilutions in sulbactam MICs was observed in 84% of the isolates when tested in combination with zidebactam. The sulbactam/zidebactam combination was able to restore sulbactam susceptibility in 91% of the isolates, including isolates that were resistant to sulbactam/avibactam combination. These data encouraged us to further explore sulbactam/zidebactam in other experimental models especially against CRAB isolates resistant to other DBOs.
publishDate 2022
dc.date.none.fl_str_mv 2022-07
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/11336/218051
Cedano, Jose; Baez, Michelle; Pasteran, Fernando; Montaña, Sabrina Daiana; Ra, Grace; et al.; Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 12; 7-2022; 1-6
2235-2988
CONICET Digital
CONICET
url http://hdl.handle.net/11336/218051
identifier_str_mv Cedano, Jose; Baez, Michelle; Pasteran, Fernando; Montaña, Sabrina Daiana; Ra, Grace; et al.; Zidebactam restores sulbactam susceptibility against carbapenem-resistant Acinetobacter baumannii isolates; Frontiers Media; Frontiers in Cellular and Infection Microbiology; 12; 7-2022; 1-6
2235-2988
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2022.918868
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 Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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