Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals

Autores
Mojica, María Fernanda; De La Cadena, Elsa; García Betancur, Juan Carlos; Porras, Jessica; Novoa Caicedo, Isabella; Páez Zamora, Laura; Pallares, Christian; Appel, Tobias Manuel; Radice, Marcela Alejandra; Castañeda Méndez, Paulo; Gales, Ana C.; Munita, José M.; Villegas, María Virginia
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Ceftazidime-avibactam (CZA) is the combination of a third-generation cephalosporin and a new non-b-lactam b-lactamase inhibitor capable of inactivating class A, C, and some D b-lactamases. From a collection of 2,727 clinical isolates of Enterobacterales (n = 2,235) and P. aeruginosa (n = 492) that were collected between 2016 and 2017 from five Latin American countries, we investigated the molecular resistance mechanisms to CZA of 127 (18/2,235 [0.8%] Enterobacterales and 109/492 [22.1%] P. aeruginosa). First, by qPCR for the presence of genes encoding KPC, NDM, VIM, IMP, OXA-48-like, and SPM-1 carbapenemases, and second, by whole-genome sequencing (WGS). From the CZA-resistant isolates, MBL-encoding genes were detected in all 18 Enterobacterales and 42/109 P. aeruginosa isolates, explaining their resistant phenotype. Resistant isolates that yielded a negative qPCR result for any of the MBL encoding genes were subjected to WGS. The WGS analysis of the 67 remaining P. aeruginosa isolates showed mutations in genes previously associated with reduced susceptibility to CZA, such as those involved in the MexAB-OprM efflux pump and AmpC (PDC) hyperproduction, PoxB (blaOXA-50-like), FtsI (PBP3), DacB (PBP4), and OprD. The results presented here offer a snapshot of the molecular epidemiological landscape for CZA resistance before the introduction of this antibiotic into the Latin American market. Therefore, these results serve as a valuable comparison tool to trace the evolution of the resistance to CZA in this carbapenemase-endemic geographical region.
Fil: Mojica, María Fernanda. Case Western Reserve University; Estados Unidos. Va Northeast Ohio Healthcare System; Estados Unidos. Universidad El Bosque;
Fil: De La Cadena, Elsa. Universidad El Bosque;
Fil: García Betancur, Juan Carlos. Universidad El Bosque;
Fil: Porras, Jessica. Universidad El Bosque;
Fil: Novoa Caicedo, Isabella. Universidad El Bosque;
Fil: Páez Zamora, Laura. Universidad El Bosque;
Fil: Pallares, Christian. Universidad El Bosque;
Fil: Appel, Tobias Manuel. Universidad El Bosque;
Fil: Radice, Marcela Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Castañeda Méndez, Paulo. Hospital San Ángel Inn Universidad; México. Fundacion Clinica Medica Sur; México
Fil: Gales, Ana C.. Universidade Federal de Sao Paulo; Brasil
Fil: Munita, José M.. Millennium Initiative for Collaborative Research on Bacterial Resistance; Chile
Fil: Villegas, María Virginia. Universidad El Bosque;
Materia
ANTIMICROBIAL RESISTANCE
CEFTAZIDIME/AVIBACTAM
ENTEROBACTERALES
LATIN AMERICA
PSEUDOMONAS AERUGINOSA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/227554
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/227554
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American HospitalsMojica, María FernandaDe La Cadena, ElsaGarcía Betancur, Juan CarlosPorras, JessicaNovoa Caicedo, IsabellaPáez Zamora, LauraPallares, ChristianAppel, Tobias ManuelRadice, Marcela AlejandraCastañeda Méndez, PauloGales, Ana C.Munita, José M.Villegas, María VirginiaANTIMICROBIAL RESISTANCECEFTAZIDIME/AVIBACTAMENTEROBACTERALESLATIN AMERICAPSEUDOMONAS AERUGINOSAhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Ceftazidime-avibactam (CZA) is the combination of a third-generation cephalosporin and a new non-b-lactam b-lactamase inhibitor capable of inactivating class A, C, and some D b-lactamases. From a collection of 2,727 clinical isolates of Enterobacterales (n = 2,235) and P. aeruginosa (n = 492) that were collected between 2016 and 2017 from five Latin American countries, we investigated the molecular resistance mechanisms to CZA of 127 (18/2,235 [0.8%] Enterobacterales and 109/492 [22.1%] P. aeruginosa). First, by qPCR for the presence of genes encoding KPC, NDM, VIM, IMP, OXA-48-like, and SPM-1 carbapenemases, and second, by whole-genome sequencing (WGS). From the CZA-resistant isolates, MBL-encoding genes were detected in all 18 Enterobacterales and 42/109 P. aeruginosa isolates, explaining their resistant phenotype. Resistant isolates that yielded a negative qPCR result for any of the MBL encoding genes were subjected to WGS. The WGS analysis of the 67 remaining P. aeruginosa isolates showed mutations in genes previously associated with reduced susceptibility to CZA, such as those involved in the MexAB-OprM efflux pump and AmpC (PDC) hyperproduction, PoxB (blaOXA-50-like), FtsI (PBP3), DacB (PBP4), and OprD. The results presented here offer a snapshot of the molecular epidemiological landscape for CZA resistance before the introduction of this antibiotic into the Latin American market. Therefore, these results serve as a valuable comparison tool to trace the evolution of the resistance to CZA in this carbapenemase-endemic geographical region.Fil: Mojica, María Fernanda. Case Western Reserve University; Estados Unidos. Va Northeast Ohio Healthcare System; Estados Unidos. Universidad El Bosque;Fil: De La Cadena, Elsa. Universidad El Bosque;Fil: García Betancur, Juan Carlos. Universidad El Bosque;Fil: Porras, Jessica. Universidad El Bosque;Fil: Novoa Caicedo, Isabella. Universidad El Bosque;Fil: Páez Zamora, Laura. Universidad El Bosque;Fil: Pallares, Christian. Universidad El Bosque;Fil: Appel, Tobias Manuel. Universidad El Bosque;Fil: Radice, Marcela Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Castañeda Méndez, Paulo. Hospital San Ángel Inn Universidad; México. Fundacion Clinica Medica Sur; MéxicoFil: Gales, Ana C.. Universidade Federal de Sao Paulo; BrasilFil: Munita, José M.. Millennium Initiative for Collaborative Research on Bacterial Resistance; ChileFil: Villegas, María Virginia. Universidad El Bosque;American Society for Microbiology2023-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/227554Mojica, María Fernanda; De La Cadena, Elsa; García Betancur, Juan Carlos; Porras, Jessica; Novoa Caicedo, Isabella; et al.; Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals; American Society for Microbiology; mSphere; 8; 2; 4-2023; 1-102379-5042CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/msphere.00651-22info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/msphere.00651-22info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:31:10Zoai:ri.conicet.gov.ar:11336/227554instacron: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 10:31:11.13CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals
title Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals
spellingShingle Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals
Mojica, María Fernanda
ANTIMICROBIAL RESISTANCE
CEFTAZIDIME/AVIBACTAM
ENTEROBACTERALES
LATIN AMERICA
PSEUDOMONAS AERUGINOSA
title_short Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals
title_full Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals
title_fullStr Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals
title_full_unstemmed Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals
title_sort Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals
dc.creator.none.fl_str_mv Mojica, María Fernanda
De La Cadena, Elsa
García Betancur, Juan Carlos
Porras, Jessica
Novoa Caicedo, Isabella
Páez Zamora, Laura
Pallares, Christian
Appel, Tobias Manuel
Radice, Marcela Alejandra
Castañeda Méndez, Paulo
Gales, Ana C.
Munita, José M.
Villegas, María Virginia
author Mojica, María Fernanda
author_facet Mojica, María Fernanda
De La Cadena, Elsa
García Betancur, Juan Carlos
Porras, Jessica
Novoa Caicedo, Isabella
Páez Zamora, Laura
Pallares, Christian
Appel, Tobias Manuel
Radice, Marcela Alejandra
Castañeda Méndez, Paulo
Gales, Ana C.
Munita, José M.
Villegas, María Virginia
author_role author
author2 De La Cadena, Elsa
García Betancur, Juan Carlos
Porras, Jessica
Novoa Caicedo, Isabella
Páez Zamora, Laura
Pallares, Christian
Appel, Tobias Manuel
Radice, Marcela Alejandra
Castañeda Méndez, Paulo
Gales, Ana C.
Munita, José M.
Villegas, María Virginia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTIMICROBIAL RESISTANCE
CEFTAZIDIME/AVIBACTAM
ENTEROBACTERALES
LATIN AMERICA
PSEUDOMONAS AERUGINOSA
topic ANTIMICROBIAL RESISTANCE
CEFTAZIDIME/AVIBACTAM
ENTEROBACTERALES
LATIN AMERICA
PSEUDOMONAS AERUGINOSA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Ceftazidime-avibactam (CZA) is the combination of a third-generation cephalosporin and a new non-b-lactam b-lactamase inhibitor capable of inactivating class A, C, and some D b-lactamases. From a collection of 2,727 clinical isolates of Enterobacterales (n = 2,235) and P. aeruginosa (n = 492) that were collected between 2016 and 2017 from five Latin American countries, we investigated the molecular resistance mechanisms to CZA of 127 (18/2,235 [0.8%] Enterobacterales and 109/492 [22.1%] P. aeruginosa). First, by qPCR for the presence of genes encoding KPC, NDM, VIM, IMP, OXA-48-like, and SPM-1 carbapenemases, and second, by whole-genome sequencing (WGS). From the CZA-resistant isolates, MBL-encoding genes were detected in all 18 Enterobacterales and 42/109 P. aeruginosa isolates, explaining their resistant phenotype. Resistant isolates that yielded a negative qPCR result for any of the MBL encoding genes were subjected to WGS. The WGS analysis of the 67 remaining P. aeruginosa isolates showed mutations in genes previously associated with reduced susceptibility to CZA, such as those involved in the MexAB-OprM efflux pump and AmpC (PDC) hyperproduction, PoxB (blaOXA-50-like), FtsI (PBP3), DacB (PBP4), and OprD. The results presented here offer a snapshot of the molecular epidemiological landscape for CZA resistance before the introduction of this antibiotic into the Latin American market. Therefore, these results serve as a valuable comparison tool to trace the evolution of the resistance to CZA in this carbapenemase-endemic geographical region.
Fil: Mojica, María Fernanda. Case Western Reserve University; Estados Unidos. Va Northeast Ohio Healthcare System; Estados Unidos. Universidad El Bosque;
Fil: De La Cadena, Elsa. Universidad El Bosque;
Fil: García Betancur, Juan Carlos. Universidad El Bosque;
Fil: Porras, Jessica. Universidad El Bosque;
Fil: Novoa Caicedo, Isabella. Universidad El Bosque;
Fil: Páez Zamora, Laura. Universidad El Bosque;
Fil: Pallares, Christian. Universidad El Bosque;
Fil: Appel, Tobias Manuel. Universidad El Bosque;
Fil: Radice, Marcela Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Castañeda Méndez, Paulo. Hospital San Ángel Inn Universidad; México. Fundacion Clinica Medica Sur; México
Fil: Gales, Ana C.. Universidade Federal de Sao Paulo; Brasil
Fil: Munita, José M.. Millennium Initiative for Collaborative Research on Bacterial Resistance; Chile
Fil: Villegas, María Virginia. Universidad El Bosque;
description Ceftazidime-avibactam (CZA) is the combination of a third-generation cephalosporin and a new non-b-lactam b-lactamase inhibitor capable of inactivating class A, C, and some D b-lactamases. From a collection of 2,727 clinical isolates of Enterobacterales (n = 2,235) and P. aeruginosa (n = 492) that were collected between 2016 and 2017 from five Latin American countries, we investigated the molecular resistance mechanisms to CZA of 127 (18/2,235 [0.8%] Enterobacterales and 109/492 [22.1%] P. aeruginosa). First, by qPCR for the presence of genes encoding KPC, NDM, VIM, IMP, OXA-48-like, and SPM-1 carbapenemases, and second, by whole-genome sequencing (WGS). From the CZA-resistant isolates, MBL-encoding genes were detected in all 18 Enterobacterales and 42/109 P. aeruginosa isolates, explaining their resistant phenotype. Resistant isolates that yielded a negative qPCR result for any of the MBL encoding genes were subjected to WGS. The WGS analysis of the 67 remaining P. aeruginosa isolates showed mutations in genes previously associated with reduced susceptibility to CZA, such as those involved in the MexAB-OprM efflux pump and AmpC (PDC) hyperproduction, PoxB (blaOXA-50-like), FtsI (PBP3), DacB (PBP4), and OprD. The results presented here offer a snapshot of the molecular epidemiological landscape for CZA resistance before the introduction of this antibiotic into the Latin American market. Therefore, these results serve as a valuable comparison tool to trace the evolution of the resistance to CZA in this carbapenemase-endemic geographical region.
publishDate 2023
dc.date.none.fl_str_mv 2023-04
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/11336/227554
Mojica, María Fernanda; De La Cadena, Elsa; García Betancur, Juan Carlos; Porras, Jessica; Novoa Caicedo, Isabella; et al.; Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals; American Society for Microbiology; mSphere; 8; 2; 4-2023; 1-10
2379-5042
CONICET Digital
CONICET
url http://hdl.handle.net/11336/227554
identifier_str_mv Mojica, María Fernanda; De La Cadena, Elsa; García Betancur, Juan Carlos; Porras, Jessica; Novoa Caicedo, Isabella; et al.; Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals; American Society for Microbiology; mSphere; 8; 2; 4-2023; 1-10
2379-5042
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/msphere.00651-22
info:eu-repo/semantics/altIdentifier/url/https://journals.asm.org/doi/10.1128/msphere.00651-22
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/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 13.070432

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