Quantifying acquisition and transmission of Enterococcus faecium using genomic surveillance

Theodore Gouliouris, Francesc Coll, Catherine Ludden, Beth Blane, Kathy E. Raven, Plamena Naydenova, Charles Crawley, Mili Estée Török, David A. Enoch, Nicholas M. Brown, Ewan M. Harrison, Julian Parkhill, Sharon Peacock*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Nosocomial acquisition and transmission of vancomycin-resistant Enterococcus faecium (VREfm) is the driver for E. faecium carriage in hospitalized patients, which, in turn, is a risk factor for invasive infection in immunocompromised patients. In the present study, we provide a comprehensive picture of E. faecium transmission in an entire sampled patient population using a sequence-driven approach. We prospectively identified and followed 149 haematology patients admitted to a hospital in England for 6 months. Patient stools (n = 376) and environmental swabs (n = 922) were taken at intervals and cultured for E. faecium. We sequenced 1,560 isolates (1,001 stool, 559 environment) and focused our genomic analyses on 1,477 isolates (95%) in the hospital-adapted clade A1. Of 101 patients who provided two or more stool samples, 40 (40%) developed E. faecium carriage after admission based on culture, compared with 64 patients (63%) based on genomic analysis (73% VREfm). Half of 922 environmental swabs (447, 48%) were positive for VREfm. Network analysis showed that, of 111 patients positive for the A1 clade, 67 had strong epidemiological and genomic links with at least one other patient and/or their direct environment, supporting nosocomial transmission. Six patients (3.4%) developed an invasive E. faecium infection from their own gut-colonizing strain, which was preceded by nosocomial acquisition of the infecting isolate in half of these. Two informatics approaches (subtype categorization to define phylogenetic clusters and the development of an SNP cut-off for transmission) were central to our analyses, both of which will inform the future translation of E. faecium sequencing into routine outbreak detection and investigation. In conclusion, we showed that carriage and environmental contamination by the hospital-adapted E. faecium lineage were hyperendemic in our study population and that improved infection control measures will be needed to reduce hospital acquisition rates.

A longitudinal genomic surveillance of Enterococcus faecium carriage, environmental contamination and transmission in a defined patient cohort shows that a hospital-adapted E. faecium lineage was hyperendemic.

Original languageEnglish
Pages (from-to)103-+
Number of pages18
JournalNature Microbiology
Volume6
Issue number1
DOIs
Publication statusPublished - Jan 2021

Bibliographical note

Funding Information:
We thank the nurses and healthcare workers on both wards at CUH for assistance with sample collection and the ward matrons, A. Green and C. Cowling, for their support. We thank L. Chaparadza and R. Swayne for assistance with sample and clinical data collection. We thank L. Drumright, A. Chaudhry and the EPIC and Clinical Informatics teams for providing patient movement data. We thank the library construction, sequencing and Pathogen Informatics teams at the Wellcome Trust Sanger Institute for assistance with Illumina sequencing. The flocked swabs were donated by Copan Italia SpA. The present study presents independent research supported by the Health Innovation Challenge Fund (WT098600, HICF-T5-342), a parallel funding partnership between the Department of Health and the Wellcome Trust. The views expressed in this article are those of the author(s) and not necessarily those of the Department of Health or Wellcome Trust. T.G. is a Wellcome Trust Research Training Fellow (103387/Z/13/Z). F.C. is a Wellcome Trust Sir Henry Postdoctoral Fellow (201344/Z/16/Z). C.L. is a Wellcome Trust Sir Henry Postdoctoral Fellow (110243/Z/15/Z). M.E.T. is a Clinician Scientist Fellow supported by the Academy of Medical Sciences, the Health Foundation and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. S.J.P. is an NIHR Senior Investigator.

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • RESISTANT ENTEROCOCCI
  • BACTEREMIA
  • RISK

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