Confronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , |
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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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:RCAAP2023-03-10T09:46:10Zoai:repositorio.chlc.min-saude.pt:10400.17/4307Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:21:38.055672Repositório 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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
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 |
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1817551784360542208 |