Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamas...

Autores
Yasmin, Mohamad; Rojas, Laura J.; Marshall, Steven H.; Hujer, Andrea M.; Cmolik, Anna; Marshall, Emma; Boucher, Helen W..; Vila, Alejandro Jose; Soldevila, Maxime; Diene, Seydina M.; Rolain, Jean Marc; Bonomo, Robert A.
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Elizabethkingia anophelis is an emerging Gram-negative nonlactose fermenter in the health care setting, where it causes life-threatening infections in immunocompromised patients. We aimed to characterize the molecular mechanisms of antimicrobial resistance and evaluate the utility of contemporary antibiotics with the intent to offer targeted therapy against an uncommonly encountered pathogen.Methods: Whole-genome sequencing (WGS) was conducted to accurately identify isolate species and elucidate the determinants of β-lactam resistance. Antimicrobial susceptibility testing was performed using broth microdilution and disk diffusion assays. To assess the functional contribution of the major metallo-β-lactamase (MBL) encoding genes to the resistance profile, bla BlaB was cloned into pBCSK(-) phagemid vector and transformed into Escherichia coli DH10B.Results: WGS identified the organism as E. anophelis. MBL genes bla BlaB-1 and bla GOB-26 were identified, in addition to bla CME-2, which encodes for an extended-spectrum β-lactamase (ESBL). Plasmids were not detected. The isolate was nonsusceptible to all commonly available β-lactams, carbapenems, newer β-lactam β-lactamase inhibitor combinations, and to the combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI). Susceptibility to the novel siderophore cephalosporin cefiderocol was determined. A BlaB-1 transformant E. coli DH10B isolate was obtained and demonstrated increased minimum inhibitory concentrations to cephalosporins, carbapenems, and CAZ-AVI, but not ATM.Conclusions: Using WGS, we accurately identified and characterized an extensively drug-resistant E. anophelis in an immunocompromised patient. Rapid evaluation of the genetic background can guide accurate susceptibility testing to better inform antimicrobial therapy selection.
Fil: Yasmin, Mohamad. Case Western Reserve University; Estados Unidos
Fil: Rojas, Laura J.. Case Western Reserve University; Estados Unidos
Fil: Marshall, Steven H.. Case Western Reserve University; Estados Unidos
Fil: Hujer, Andrea M.. Case Western Reserve University; Estados Unidos
Fil: Cmolik, Anna. Case Western Reserve University; Estados Unidos
Fil: Marshall, Emma. Case Western Reserve University; Estados Unidos
Fil: Boucher, Helen W... No especifíca;
Fil: Vila, Alejandro Jose. 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: Soldevila, Maxime. No especifíca;
Fil: Diene, Seydina M.. Case Western Reserve University; Estados Unidos
Fil: Rolain, Jean Marc. No especifíca;
Fil: Bonomo, Robert A.. Case Western Reserve University; Estados Unidos
Materia
Elizabethkingia
cefiderocol
metallo-β-lactamase
whole-genome sequencing.
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:11336/255847

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase InhibitorsYasmin, MohamadRojas, Laura J.Marshall, Steven H.Hujer, Andrea M.Cmolik, AnnaMarshall, EmmaBoucher, Helen W..Vila, Alejandro JoseSoldevila, MaximeDiene, Seydina M.Rolain, Jean MarcBonomo, Robert A.Elizabethkingiacefiderocolmetallo-β-lactamasewhole-genome sequencing.https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Background: Elizabethkingia anophelis is an emerging Gram-negative nonlactose fermenter in the health care setting, where it causes life-threatening infections in immunocompromised patients. We aimed to characterize the molecular mechanisms of antimicrobial resistance and evaluate the utility of contemporary antibiotics with the intent to offer targeted therapy against an uncommonly encountered pathogen.Methods: Whole-genome sequencing (WGS) was conducted to accurately identify isolate species and elucidate the determinants of β-lactam resistance. Antimicrobial susceptibility testing was performed using broth microdilution and disk diffusion assays. To assess the functional contribution of the major metallo-β-lactamase (MBL) encoding genes to the resistance profile, bla BlaB was cloned into pBCSK(-) phagemid vector and transformed into Escherichia coli DH10B.Results: WGS identified the organism as E. anophelis. MBL genes bla BlaB-1 and bla GOB-26 were identified, in addition to bla CME-2, which encodes for an extended-spectrum β-lactamase (ESBL). Plasmids were not detected. The isolate was nonsusceptible to all commonly available β-lactams, carbapenems, newer β-lactam β-lactamase inhibitor combinations, and to the combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI). Susceptibility to the novel siderophore cephalosporin cefiderocol was determined. A BlaB-1 transformant E. coli DH10B isolate was obtained and demonstrated increased minimum inhibitory concentrations to cephalosporins, carbapenems, and CAZ-AVI, but not ATM.Conclusions: Using WGS, we accurately identified and characterized an extensively drug-resistant E. anophelis in an immunocompromised patient. Rapid evaluation of the genetic background can guide accurate susceptibility testing to better inform antimicrobial therapy selection.Fil: Yasmin, Mohamad. Case Western Reserve University; Estados UnidosFil: Rojas, Laura J.. Case Western Reserve University; Estados UnidosFil: Marshall, Steven H.. Case Western Reserve University; Estados UnidosFil: Hujer, Andrea M.. Case Western Reserve University; Estados UnidosFil: Cmolik, Anna. Case Western Reserve University; Estados UnidosFil: Marshall, Emma. Case Western Reserve University; Estados UnidosFil: Boucher, Helen W... No especifíca;Fil: Vila, Alejandro Jose. 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: Soldevila, Maxime. No especifíca;Fil: Diene, Seydina M.. Case Western Reserve University; Estados UnidosFil: Rolain, Jean Marc. No especifíca;Fil: Bonomo, Robert A.. Case Western Reserve University; Estados UnidosOxford University Press2023-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/255847Yasmin, Mohamad; Rojas, Laura J.; Marshall, Steven H.; Hujer, Andrea M.; Cmolik, Anna; et al.; Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors; Oxford University Press; Open Forum Infectious Diseases; 10; 2; 2-2023; 1-82328-8957CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/ofid/article/doi/10.1093/ofid/ofad014/7016775info:eu-repo/semantics/altIdentifier/doi/10.1093/ofid/ofad014info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:10Zoai:ri.conicet.gov.ar:11336/255847instacron: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 09:59:10.986CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
title Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
spellingShingle Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
Yasmin, Mohamad
Elizabethkingia
cefiderocol
metallo-β-lactamase
whole-genome sequencing.
title_short Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
title_full Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
title_fullStr Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
title_full_unstemmed Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
title_sort Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
dc.creator.none.fl_str_mv Yasmin, Mohamad
Rojas, Laura J.
Marshall, Steven H.
Hujer, Andrea M.
Cmolik, Anna
Marshall, Emma
Boucher, Helen W..
Vila, Alejandro Jose
Soldevila, Maxime
Diene, Seydina M.
Rolain, Jean Marc
Bonomo, Robert A.
author Yasmin, Mohamad
author_facet Yasmin, Mohamad
Rojas, Laura J.
Marshall, Steven H.
Hujer, Andrea M.
Cmolik, Anna
Marshall, Emma
Boucher, Helen W..
Vila, Alejandro Jose
Soldevila, Maxime
Diene, Seydina M.
Rolain, Jean Marc
Bonomo, Robert A.
author_role author
author2 Rojas, Laura J.
Marshall, Steven H.
Hujer, Andrea M.
Cmolik, Anna
Marshall, Emma
Boucher, Helen W..
Vila, Alejandro Jose
Soldevila, Maxime
Diene, Seydina M.
Rolain, Jean Marc
Bonomo, Robert A.
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Elizabethkingia
cefiderocol
metallo-β-lactamase
whole-genome sequencing.
topic Elizabethkingia
cefiderocol
metallo-β-lactamase
whole-genome sequencing.
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Elizabethkingia anophelis is an emerging Gram-negative nonlactose fermenter in the health care setting, where it causes life-threatening infections in immunocompromised patients. We aimed to characterize the molecular mechanisms of antimicrobial resistance and evaluate the utility of contemporary antibiotics with the intent to offer targeted therapy against an uncommonly encountered pathogen.Methods: Whole-genome sequencing (WGS) was conducted to accurately identify isolate species and elucidate the determinants of β-lactam resistance. Antimicrobial susceptibility testing was performed using broth microdilution and disk diffusion assays. To assess the functional contribution of the major metallo-β-lactamase (MBL) encoding genes to the resistance profile, bla BlaB was cloned into pBCSK(-) phagemid vector and transformed into Escherichia coli DH10B.Results: WGS identified the organism as E. anophelis. MBL genes bla BlaB-1 and bla GOB-26 were identified, in addition to bla CME-2, which encodes for an extended-spectrum β-lactamase (ESBL). Plasmids were not detected. The isolate was nonsusceptible to all commonly available β-lactams, carbapenems, newer β-lactam β-lactamase inhibitor combinations, and to the combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI). Susceptibility to the novel siderophore cephalosporin cefiderocol was determined. A BlaB-1 transformant E. coli DH10B isolate was obtained and demonstrated increased minimum inhibitory concentrations to cephalosporins, carbapenems, and CAZ-AVI, but not ATM.Conclusions: Using WGS, we accurately identified and characterized an extensively drug-resistant E. anophelis in an immunocompromised patient. Rapid evaluation of the genetic background can guide accurate susceptibility testing to better inform antimicrobial therapy selection.
Fil: Yasmin, Mohamad. Case Western Reserve University; Estados Unidos
Fil: Rojas, Laura J.. Case Western Reserve University; Estados Unidos
Fil: Marshall, Steven H.. Case Western Reserve University; Estados Unidos
Fil: Hujer, Andrea M.. Case Western Reserve University; Estados Unidos
Fil: Cmolik, Anna. Case Western Reserve University; Estados Unidos
Fil: Marshall, Emma. Case Western Reserve University; Estados Unidos
Fil: Boucher, Helen W... No especifíca;
Fil: Vila, Alejandro Jose. 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: Soldevila, Maxime. No especifíca;
Fil: Diene, Seydina M.. Case Western Reserve University; Estados Unidos
Fil: Rolain, Jean Marc. No especifíca;
Fil: Bonomo, Robert A.. Case Western Reserve University; Estados Unidos
description Background: Elizabethkingia anophelis is an emerging Gram-negative nonlactose fermenter in the health care setting, where it causes life-threatening infections in immunocompromised patients. We aimed to characterize the molecular mechanisms of antimicrobial resistance and evaluate the utility of contemporary antibiotics with the intent to offer targeted therapy against an uncommonly encountered pathogen.Methods: Whole-genome sequencing (WGS) was conducted to accurately identify isolate species and elucidate the determinants of β-lactam resistance. Antimicrobial susceptibility testing was performed using broth microdilution and disk diffusion assays. To assess the functional contribution of the major metallo-β-lactamase (MBL) encoding genes to the resistance profile, bla BlaB was cloned into pBCSK(-) phagemid vector and transformed into Escherichia coli DH10B.Results: WGS identified the organism as E. anophelis. MBL genes bla BlaB-1 and bla GOB-26 were identified, in addition to bla CME-2, which encodes for an extended-spectrum β-lactamase (ESBL). Plasmids were not detected. The isolate was nonsusceptible to all commonly available β-lactams, carbapenems, newer β-lactam β-lactamase inhibitor combinations, and to the combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI). Susceptibility to the novel siderophore cephalosporin cefiderocol was determined. A BlaB-1 transformant E. coli DH10B isolate was obtained and demonstrated increased minimum inhibitory concentrations to cephalosporins, carbapenems, and CAZ-AVI, but not ATM.Conclusions: Using WGS, we accurately identified and characterized an extensively drug-resistant E. anophelis in an immunocompromised patient. Rapid evaluation of the genetic background can guide accurate susceptibility testing to better inform antimicrobial therapy selection.
publishDate 2023
dc.date.none.fl_str_mv 2023-02
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/11336/255847
Yasmin, Mohamad; Rojas, Laura J.; Marshall, Steven H.; Hujer, Andrea M.; Cmolik, Anna; et al.; Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors; Oxford University Press; Open Forum Infectious Diseases; 10; 2; 2-2023; 1-8
2328-8957
CONICET Digital
CONICET
url http://hdl.handle.net/11336/255847
identifier_str_mv Yasmin, Mohamad; Rojas, Laura J.; Marshall, Steven H.; Hujer, Andrea M.; Cmolik, Anna; et al.; Characterization of a Novel Pathogen in Immunocompromised Patients: Elizabethkingia anophelis —Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors; Oxford University Press; Open Forum Infectious Diseases; 10; 2; 2-2023; 1-8
2328-8957
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://academic.oup.com/ofid/article/doi/10.1093/ofid/ofad014/7016775
info:eu-repo/semantics/altIdentifier/doi/10.1093/ofid/ofad014
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 Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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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