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

2021Journal article Open access
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dc.contributor.authorHernández-García, M
dc.contributor.authorGarcía-Fernández, S
dc.contributor.authorGarcía-Castillo, M
dc.contributor.authorMelo-Cristino, J
dc.contributor.authorPinto, M
dc.contributor.authorGonçalves, E
dc.contributor.authorAlves, V
dc.contributor.authorCosta, E
dc.contributor.authorRamalheira, E
dc.contributor.authorSancho, L
dc.contributor.authorDiogo, J
dc.contributor.authorFerreira, R
dc.contributor.authorSilva, T
dc.contributor.authorChaves, C
dc.contributor.authorPássaro, L
dc.contributor.authorPaixão, L
dc.contributor.authorRomano, J
dc.contributor.authorCantón, J
dc.contributor.authorSTEP Study Group
dc.date.accessioned2022-12-07T15:55:39Z
dc.date.available2022-12-07T15:55:39Z
dc.date.issued2021
dc.description.abstractCeftolozane-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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Antimicrob Agents. 2021 Feb;57(2):106259. doi: 10.1016/j.ijantimicag.2020.106259.pt_PT
dc.identifier.doi10.1016/j.ijantimicag.2020.106259pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/4307
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.subjectCHLC ANPATpt_PT
dc.subjectAnti-Bacterial Agents / pharmacology*pt_PT
dc.subjectBacterial Proteins / geneticspt_PT
dc.subjectCephalosporins / pharmacology*pt_PT
dc.subjectDrug Resistance, Multiple, Bacterial / geneticspt_PT
dc.subjectEnterobacteriaceae / drug effects*pt_PT
dc.subjectEnterobacteriaceae / geneticspt_PT
dc.subjectEnterobacteriaceae / isolation & purificationpt_PT
dc.subjectEnterobacteriaceae Infections / microbiologypt_PT
dc.subjectEscherichia coli / drug effects*pt_PT
dc.subjectEscherichia coli / geneticspt_PT
dc.subjectEscherichia coli / isolation & purificationpt_PT
dc.subjectEscherichia coli / pathogenicitypt_PT
dc.subjectEscherichia coli Infections / microbiologypt_PT
dc.subjectHumanspt_PT
dc.subjectGenome, Bacterialpt_PT
dc.subjectKlebsiella / drug effects*pt_PT
dc.subjectKlebsiella / geneticspt_PT
dc.subjectKlebsiella / isolation & purificationpt_PT
dc.subjectKlebsiella / pathogenicitypt_PT
dc.subjectKlebsiella Infections / microbiologypt_PT
dc.subjectKlebsiella pneumoniae / drug effectspt_PT
dc.subjectKlebsiella pneumoniae / geneticspt_PT
dc.subjectKlebsiella pneumoniae / isolation & purificationpt_PT
dc.subjectKlebsiella pneumoniae / pathogenicitypt_PT
dc.subjectMicrobial Sensitivity Testspt_PT
dc.subjectTazobactam / pharmacology*pt_PT
dc.subjectVirulence / geneticspt_PT
dc.subjectWhole Genome Sequencingpt_PT
dc.subjectBeta-Lactamases / geneticspt_PT
dc.titleConfronting Ceftolozane-Tazobactam Susceptibility in Multidrug-Resistant Enterobacterales Isolates and Whole-Genome Sequencing Results (STEP Study)pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleInternational Journal of Antimicrobial Agentspt_PT
oaire.citation.volume57pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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