Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)

Detalhes bibliográficos
Autor(a) principal: Hernández-García, M
Data de Publicação: 2021
Outros Autores: García-Fernández, S, García-Castillo, M, Melo-Cristino, J, Pinto, M, Gonçalves, E, Alves, V, Costa, E, Ramalheira, E, Sancho, L, Diogo, J, Ferreira, R, Silva, T, Chaves, C, Pássaro, L, Paixão, L, Romano, J, Cantón, J, STEP Study Group
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.17/4307
Resumo: Ceftolozane-tazobactam (C/T) is frequently used for infections caused by multidrug-resistant (MDR)-Enterobacterales isolates. Whole-genome sequencing (WGS, Illumina-Hiseq 4000/NovaSeq 6000, OGC, UK) was used to study the population structure, the resistome and the virulome of C/T-susceptible and -resistant MDR Escherichia spp. (n=30) and Klebsiella spp. (n=78) isolates, recovered from lower respiratory, intra-abdominal and urinary tract infections of ICU patients from 11 Portuguese Hospitals (STEP study, 2017-2018). Minimum inhibitory concentrations (MICs) were determined (ISO-broth microdilution, breakpoints EUCAST-2020). In Escherichia spp., a weak concordance between the phenotypic and the WGS method (P=0.051) was observed in the carbapenemase detection (3/30) [blaVIM-2 (2/3), blaKPC-3 (1/3)]; VIM-2-Escherichia coli isolates were C/T-susceptible and only the KPC-3-Escherichia marmotae producer showed C/T-resistance. Overall, CTX-M-15-E. coli-ST131-O25:H4-H30-Rx (11/30) was the most frequent subclone, followed by CTX-M-27-E. coli-ST131-O25:H4-H30 (4/4). Moreover, a wide resistome and virulome were detected in all E. coli isolates. Among Klebsiella spp. isolates [K. pneumoniae (67/78), K. aerogenes (7/78), K. oxytoca (2/78), K. variicola (2/78)], concordance (P<0.001) was observed between the phenotypic and the genomic carbapenemase detection (21/78) [blaKPC-3 (14/21), blaOXA-48 (3/21), blaOXA-181 (3/21)]. A high correlation between C/T-resistance and carbapenemase detection was established (P<0.05). Overall, a high clonal diversity was observed, mainly in KPC-3-producing K. pneumoniae isolates. An extensive resistome was detected in Klebsiella spp. isolates, whereas virulence determinants were mostly identified in carbapenemase producers (P<0.001). WGS is a powerful tool for typing characterization and microbiological study of MDR-Enterobacterales pathogens. Furthermore, carbapenemase genes are associated with C/T-resistance in Klebsiella spp., but other mechanisms might also be involved.
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spelling Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)CHLC ANPATAnti-Bacterial Agents / pharmacology*Bacterial Proteins / geneticsCephalosporins / pharmacology*Drug Resistance, Multiple, Bacterial / geneticsEnterobacteriaceae / drug effects*Enterobacteriaceae / geneticsEnterobacteriaceae / isolation & purificationEnterobacteriaceae Infections / microbiologyEscherichia coli / drug effects*Escherichia coli / geneticsEscherichia coli / isolation & purificationEscherichia coli / pathogenicityEscherichia coli Infections / microbiologyHumansGenome, BacterialKlebsiella / drug effects*Klebsiella / geneticsKlebsiella / isolation & purificationKlebsiella / pathogenicityKlebsiella Infections / microbiologyKlebsiella pneumoniae / drug effectsKlebsiella pneumoniae / geneticsKlebsiella pneumoniae / isolation & purificationKlebsiella pneumoniae / pathogenicityMicrobial Sensitivity TestsTazobactam / pharmacology*Virulence / geneticsWhole Genome SequencingBeta-Lactamases / geneticsCeftolozane-tazobactam (C/T) is frequently used for infections caused by multidrug-resistant (MDR)-Enterobacterales isolates. Whole-genome sequencing (WGS, Illumina-Hiseq 4000/NovaSeq 6000, OGC, UK) was used to study the population structure, the resistome and the virulome of C/T-susceptible and -resistant MDR Escherichia spp. (n=30) and Klebsiella spp. (n=78) isolates, recovered from lower respiratory, intra-abdominal and urinary tract infections of ICU patients from 11 Portuguese Hospitals (STEP study, 2017-2018). Minimum inhibitory concentrations (MICs) were determined (ISO-broth microdilution, breakpoints EUCAST-2020). In Escherichia spp., a weak concordance between the phenotypic and the WGS method (P=0.051) was observed in the carbapenemase detection (3/30) [blaVIM-2 (2/3), blaKPC-3 (1/3)]; VIM-2-Escherichia coli isolates were C/T-susceptible and only the KPC-3-Escherichia marmotae producer showed C/T-resistance. Overall, CTX-M-15-E. coli-ST131-O25:H4-H30-Rx (11/30) was the most frequent subclone, followed by CTX-M-27-E. coli-ST131-O25:H4-H30 (4/4). Moreover, a wide resistome and virulome were detected in all E. coli isolates. Among Klebsiella spp. isolates [K. pneumoniae (67/78), K. aerogenes (7/78), K. oxytoca (2/78), K. variicola (2/78)], concordance (P<0.001) was observed between the phenotypic and the genomic carbapenemase detection (21/78) [blaKPC-3 (14/21), blaOXA-48 (3/21), blaOXA-181 (3/21)]. A high correlation between C/T-resistance and carbapenemase detection was established (P<0.05). Overall, a high clonal diversity was observed, mainly in KPC-3-producing K. pneumoniae isolates. An extensive resistome was detected in Klebsiella spp. isolates, whereas virulence determinants were mostly identified in carbapenemase producers (P<0.001). WGS is a powerful tool for typing characterization and microbiological study of MDR-Enterobacterales pathogens. Furthermore, carbapenemase genes are associated with C/T-resistance in Klebsiella spp., but other mechanisms might also be involved.ElsevierRepositório do Centro Hospitalar Universitário de Lisboa Central, EPEHernández-García, MGarcía-Fernández, SGarcía-Castillo, MMelo-Cristino, JPinto, MGonçalves, EAlves, VCosta, ERamalheira, ESancho, LDiogo, JFerreira, RSilva, TChaves, CPássaro, LPaixão, LRomano, JCantón, JSTEP Study Group2022-12-07T15:55:39Z20212021-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/4307engInt J Antimicrob Agents. 2021 Feb;57(2):106259. doi: 10.1016/j.ijantimicag.2020.106259.10.1016/j.ijantimicag.2020.106259info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-10-28T10:30:33Zoai:repositorio.chlc.pt:10400.17/4307Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-10-28T10:30:33Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)
title Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)
spellingShingle Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)
Hernández-García, M
CHLC ANPAT
Anti-Bacterial Agents / pharmacology*
Bacterial Proteins / genetics
Cephalosporins / pharmacology*
Drug Resistance, Multiple, Bacterial / genetics
Enterobacteriaceae / drug effects*
Enterobacteriaceae / genetics
Enterobacteriaceae / isolation & purification
Enterobacteriaceae Infections / microbiology
Escherichia coli / drug effects*
Escherichia coli / genetics
Escherichia coli / isolation & purification
Escherichia coli / pathogenicity
Escherichia coli Infections / microbiology
Humans
Genome, Bacterial
Klebsiella / drug effects*
Klebsiella / genetics
Klebsiella / isolation & purification
Klebsiella / pathogenicity
Klebsiella Infections / microbiology
Klebsiella pneumoniae / drug effects
Klebsiella pneumoniae / genetics
Klebsiella pneumoniae / isolation & purification
Klebsiella pneumoniae / pathogenicity
Microbial Sensitivity Tests
Tazobactam / pharmacology*
Virulence / genetics
Whole Genome Sequencing
Beta-Lactamases / genetics
title_short Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)
title_full Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)
title_fullStr Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)
title_full_unstemmed Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)
title_sort Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)
author Hernández-García, M
author_facet Hernández-García, M
García-Fernández, S
García-Castillo, M
Melo-Cristino, J
Pinto, M
Gonçalves, E
Alves, V
Costa, E
Ramalheira, E
Sancho, L
Diogo, J
Ferreira, R
Silva, T
Chaves, C
Pássaro, L
Paixão, L
Romano, J
Cantón, J
STEP Study Group
author_role author
author2 García-Fernández, S
García-Castillo, M
Melo-Cristino, J
Pinto, M
Gonçalves, E
Alves, V
Costa, E
Ramalheira, E
Sancho, L
Diogo, J
Ferreira, R
Silva, T
Chaves, C
Pássaro, L
Paixão, L
Romano, J
Cantón, J
STEP Study Group
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE
dc.contributor.author.fl_str_mv Hernández-García, M
García-Fernández, S
García-Castillo, M
Melo-Cristino, J
Pinto, M
Gonçalves, E
Alves, V
Costa, E
Ramalheira, E
Sancho, L
Diogo, J
Ferreira, R
Silva, T
Chaves, C
Pássaro, L
Paixão, L
Romano, J
Cantón, J
STEP Study Group
dc.subject.por.fl_str_mv CHLC ANPAT
Anti-Bacterial Agents / pharmacology*
Bacterial Proteins / genetics
Cephalosporins / pharmacology*
Drug Resistance, Multiple, Bacterial / genetics
Enterobacteriaceae / drug effects*
Enterobacteriaceae / genetics
Enterobacteriaceae / isolation & purification
Enterobacteriaceae Infections / microbiology
Escherichia coli / drug effects*
Escherichia coli / genetics
Escherichia coli / isolation & purification
Escherichia coli / pathogenicity
Escherichia coli Infections / microbiology
Humans
Genome, Bacterial
Klebsiella / drug effects*
Klebsiella / genetics
Klebsiella / isolation & purification
Klebsiella / pathogenicity
Klebsiella Infections / microbiology
Klebsiella pneumoniae / drug effects
Klebsiella pneumoniae / genetics
Klebsiella pneumoniae / isolation & purification
Klebsiella pneumoniae / pathogenicity
Microbial Sensitivity Tests
Tazobactam / pharmacology*
Virulence / genetics
Whole Genome Sequencing
Beta-Lactamases / genetics
topic CHLC ANPAT
Anti-Bacterial Agents / pharmacology*
Bacterial Proteins / genetics
Cephalosporins / pharmacology*
Drug Resistance, Multiple, Bacterial / genetics
Enterobacteriaceae / drug effects*
Enterobacteriaceae / genetics
Enterobacteriaceae / isolation & purification
Enterobacteriaceae Infections / microbiology
Escherichia coli / drug effects*
Escherichia coli / genetics
Escherichia coli / isolation & purification
Escherichia coli / pathogenicity
Escherichia coli Infections / microbiology
Humans
Genome, Bacterial
Klebsiella / drug effects*
Klebsiella / genetics
Klebsiella / isolation & purification
Klebsiella / pathogenicity
Klebsiella Infections / microbiology
Klebsiella pneumoniae / drug effects
Klebsiella pneumoniae / genetics
Klebsiella pneumoniae / isolation & purification
Klebsiella pneumoniae / pathogenicity
Microbial Sensitivity Tests
Tazobactam / pharmacology*
Virulence / genetics
Whole Genome Sequencing
Beta-Lactamases / genetics
description Ceftolozane-tazobactam (C/T) is frequently used for infections caused by multidrug-resistant (MDR)-Enterobacterales isolates. Whole-genome sequencing (WGS, Illumina-Hiseq 4000/NovaSeq 6000, OGC, UK) was used to study the population structure, the resistome and the virulome of C/T-susceptible and -resistant MDR Escherichia spp. (n=30) and Klebsiella spp. (n=78) isolates, recovered from lower respiratory, intra-abdominal and urinary tract infections of ICU patients from 11 Portuguese Hospitals (STEP study, 2017-2018). Minimum inhibitory concentrations (MICs) were determined (ISO-broth microdilution, breakpoints EUCAST-2020). In Escherichia spp., a weak concordance between the phenotypic and the WGS method (P=0.051) was observed in the carbapenemase detection (3/30) [blaVIM-2 (2/3), blaKPC-3 (1/3)]; VIM-2-Escherichia coli isolates were C/T-susceptible and only the KPC-3-Escherichia marmotae producer showed C/T-resistance. Overall, CTX-M-15-E. coli-ST131-O25:H4-H30-Rx (11/30) was the most frequent subclone, followed by CTX-M-27-E. coli-ST131-O25:H4-H30 (4/4). Moreover, a wide resistome and virulome were detected in all E. coli isolates. Among Klebsiella spp. isolates [K. pneumoniae (67/78), K. aerogenes (7/78), K. oxytoca (2/78), K. variicola (2/78)], concordance (P<0.001) was observed between the phenotypic and the genomic carbapenemase detection (21/78) [blaKPC-3 (14/21), blaOXA-48 (3/21), blaOXA-181 (3/21)]. A high correlation between C/T-resistance and carbapenemase detection was established (P<0.05). Overall, a high clonal diversity was observed, mainly in KPC-3-producing K. pneumoniae isolates. An extensive resistome was detected in Klebsiella spp. isolates, whereas virulence determinants were mostly identified in carbapenemase producers (P<0.001). WGS is a powerful tool for typing characterization and microbiological study of MDR-Enterobacterales pathogens. Furthermore, carbapenemase genes are associated with C/T-resistance in Klebsiella spp., but other mechanisms might also be involved.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01T00:00:00Z
2022-12-07T15:55:39Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.17/4307
url http://hdl.handle.net/10400.17/4307
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Int J Antimicrob Agents. 2021 Feb;57(2):106259. doi: 10.1016/j.ijantimicag.2020.106259.
10.1016/j.ijantimicag.2020.106259
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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