1887

Abstract

The emergence of vancomycin-resistant (VREfm) has left the vancomycin-sensitive (VSEfm) strains almost unnoticed.

Molecular characteristics, hospital transmission patterns and clinical impact of VSEfm have changed, and VSEfm is a predictor of VREfm introduction.

We wanted to do a molecular characterization of VSEfm to identify hospital transmissions and links between VSEfm and VREfm, and to investigate the demographics, treatment and impact on mortality of VSEfm bacteraemia.

VSEfm and VREfm blood culture isolates from Odense University Hospital, Denmark, from 2015 to 2019 were characterized using whole-genome sequencing and core-genome multilocus sequence typing (cgMLST). Clonal shifts and diversity of the VREfm isolates were compared to the VSEfm isolates. Hospital records were used for clinical data and transmission investigation of VSEfm cases.

Six-hundred and thirty VSEfm isolates from 599 patients belonged to 42 sequence types (STs) and 131 complex types (CTs) in several clusters. Multiple types were involved in putative transmission, occurring over the entire period. Twenty-seven VREfm bacteraemia cases were included. No correlation between the VSEfm and VREfm clones was identified. The 30 day mortality was 40 %, but only in 6.3 % of the cases, VSEfm bacteraemia was the likely cause of death.

The molecular types of VSEfm bacteraemia isolates are changing and diverse. No direct correlation between VSEfm and the introduction of VREfm was found, but widespread hospital transmission indicates a presence of risk factors that could facilitate transmission of other micro-organisms as well. VSEfm bacteraemia is rarely the cause of death, indicating that 30 day mortality does not reflect the cause of death.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001731
2023-07-12
2024-05-04
Loading full text...

Full text loading...

/deliver/fulltext/jmm/72/7/jmm001731.html?itemId=/content/journal/jmm/10.1099/jmm.0.001731&mimeType=html&fmt=ahah

References

  1. Fiore E, Van Tyne D, Gilmore MS. Pathogenicity of enterococci. Microbiol Spectr 2019; 7:gpp3-0053-2018 [View Article] [PubMed]
    [Google Scholar]
  2. Arias CA, Murray BE. The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 2012; 10:266–278 [View Article] [PubMed]
    [Google Scholar]
  3. Rice LB. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis 2008; 197:1079–1081 [View Article] [PubMed]
    [Google Scholar]
  4. Wagenvoort JHT, De Brauwer E, Penders RJR, Willems RJ, Top J et al. Environmental survival of vancomycin-resistant Enterococcus faecium. J Hosp Infect 2011; 77:282–283 [View Article] [PubMed]
    [Google Scholar]
  5. Otter JA, Vickery K, Walker JT, deLancey Pulcini E, Stoodley P et al. Surface-attached cells, biofilms and biocide susceptibility: implications for hospital cleaning and disinfection. J Hosp Infect 2015; 89:16–27 [View Article] [PubMed]
    [Google Scholar]
  6. Coque TM, Willems RJL, Fortún J, Top J, Diz S et al. Population structure of Enterococcus faecium causing bacteremia in a Spanish university hospital: setting the scene for a future increase in vancomycin resistance?. Antimicrob Agents Chemother 2005; 49:2693–2700 [View Article] [PubMed]
    [Google Scholar]
  7. Leavis HL, Bonten MJM, Willems RJL. Identification of high-risk enterococcal clonal complexes: global dispersion and antibiotic resistance. Curr Opin Microbiol 2006; 9:454–460 [View Article] [PubMed]
    [Google Scholar]
  8. Top J, Willems R, van der Velden S, Asbroek M, Bonten M. Emergence of clonal complex 17 Enterococcus faecium in the Netherlands. J Clin Microbiol 2008; 46:214–219 [View Article] [PubMed]
    [Google Scholar]
  9. Lester CH, Sandvang D, Olsen SS, Schønheyder HC, Jarløv JO et al. Emergence of ampicillin-resistant Enterococcus faecium in Danish hospitals. J Antimicrob Chemother 2008; 62:1203–1206 [View Article] [PubMed]
    [Google Scholar]
  10. Galloway-Peña J, Roh JH, Latorre M, Qin X, Murray BE. Genomic and SNP analyses demonstrate a distant separation of the hospital and community-associated clades of Enterococcus faecium. PLoS One 2012; 7:e30187 [View Article] [PubMed]
    [Google Scholar]
  11. Willems RJL, Top J, van Schaik W, Leavis H, Bonten M et al. Restricted gene flow among hospital subpopulations of Enterococcus faecium. mBio 2012; 3:e00151-12 [View Article] [PubMed]
    [Google Scholar]
  12. Lebreton F, van Schaik W, McGuire AM, Godfrey P, Griggs A et al. Emergence of epidemic multidrug-resistant Enterococcus faecium from animal and commensal strains. mBio 2013; 4:e00534-13 [View Article] [PubMed]
    [Google Scholar]
  13. DANMAP DANMAP Reports ( https://www.DANMAP.org/reports) Lyngby, Copenhagen: Technical University of Denmark, Statens Serum Institut; 2022
    [Google Scholar]
  14. Raven KE, Gouliouris T, Brodrick H, Coll F, Brown NM et al. Complex routes of nosocomial vancomycin-resistant Enterococcus faecium transmission revealed by genome sequencing. Clin Infect Dis 2017; 64:886–893 [View Article] [PubMed]
    [Google Scholar]
  15. van Hal SJ, Willems RJL, Gouliouris T, Ballard SA, Coque TM et al. The interplay between community and hospital Enterococcus faecium clones within health-care settings: a genomic analysis. Lancet Microbe 2022; 3:e133–e141 [View Article] [PubMed]
    [Google Scholar]
  16. Belloso Daza MV, Almeida-Santos AC, Novais C, Read A, Alves V et al. Distinction between Enterococcus faecium and Enterococcus lactis by a gluP PCR-based assay for accurate identification and diagnostics. Microbiol Spectr 2022; 10:e0326822 [View Article] [PubMed]
    [Google Scholar]
  17. de Been M, Pinholt M, Top J, Bletz S, Mellmann A et al. Core genome multilocus sequence typing scheme for high-resolution typing of Enterococcus faecium. J Clin Microbiol 2015; 53:3788–3797 [View Article] [PubMed]
    [Google Scholar]
  18. Mellmann A, Bletz S, Böking T, Kipp F, Becker K et al. Real-time genome sequencing of resistant bacteria provides precision infection control in an institutional setting. J Clin Microbiol 2016; 54:2874–2881 [View Article] [PubMed]
    [Google Scholar]
  19. van Hal SJ, Ip CLC, Ansari MA, Wilson DJ, Espedido BA et al. Evolutionary dynamics of Enterococcus faecium reveals complex genomic relationships between isolates with independent emergence of vancomycin resistance. Microb Genom 2016; 2:e000048 [View Article] [PubMed]
    [Google Scholar]
  20. Jensen LB, Garcia-Migura L, Valenzuela AJS, Løhr M, Hasman H et al. A classification system for plasmids from enterococci and other Gram-positive bacteria. J Microbiol Methods 2010; 80:25–43 [View Article] [PubMed]
    [Google Scholar]
  21. DANMAP DANMAP 2018 – Use of Antimicrobial Agents and Occurrence of Antimicrobial Resistance in Bacteria from Food Animals, Food and Humans in Denmark (www.DANMAP.org) Lyngby, Copenhagen: Technical University of Denmark, Statens Serum Institut; 2019
    [Google Scholar]
  22. Hammerum AM, Justesen US, Pinholt M, Roer L, Kaya H et al. Surveillance of vancomycin-resistant enterococci reveals shift in dominating clones and national spread of a vancomycin-variable vanA Enterococcus faecium ST1421-CT1134 clone, Denmark, 2015 to March 2019. Euro Surveill 2019; 24:1900503 [View Article] [PubMed]
    [Google Scholar]
  23. Kjær Hansen S, Andersen L, Detlefsen M, Holm A, Roer L et al. Using core genome multilocus sequence typing (cgMLST) for vancomycin-resistant Enterococcus faecium isolates to guide infection control interventions and end an outbreak. J Glob Antimicrob Resist 2021; 24:418–423 [View Article] [PubMed]
    [Google Scholar]
  24. Thomsen MCF, Ahrenfeldt J, Cisneros JLB, Jurtz V, Larsen MV et al. A bacterial analysis platform: an integrated system for analysing bacterial whole genome sequencing data for clinical diagnostics and surveillance. PLoS One 2016; 11:e0157718 [View Article] [PubMed]
    [Google Scholar]
  25. Agudelo Higuita NI, Huycke MM. Enterococcal disease, epidemiology, and implications for treatment. In Enterococci: From Commensals to Leading Causes of Drug Resistant Infection Boston, MA: Massachusetts Eye and Ear Infirmary; 2014 [PubMed]
    [Google Scholar]
  26. Bright M, Parfitt EC, Pasquill K, Steele L, Laupland KB. Occurrence and determinants of enterococcal bloodstream infections: a population-based study. Infect Dis 2020; 52:638–643 [View Article] [PubMed]
    [Google Scholar]
  27. Ali GA, Goravey W, Najim MS, Shunnar KM, Ibrahim SI et al. Epidemiology, microbiological and clinical characteristics of Enterococcus species bloodstream infections: a 10-year retrospective cohort study from Qatar. Ann Med Surg 2022; 80:104258 [View Article] [PubMed]
    [Google Scholar]
  28. Prematunge C, MacDougall C, Johnstone J, Adomako K, Lam F et al. VRE and VSE bacteremia outcomes in the era of effective VRE therapy: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 2016; 37:26–35 [View Article] [PubMed]
    [Google Scholar]
  29. López-Luis BA, Sifuentes-Osornio J, Lambraño-Castillo D, Ortiz-Brizuela E, Ramírez-Fontes A et al. Risk factors and outcomes associated with vancomycin-resistant Enterococcus faecium and ampicillin-resistant Enterococcus faecalis bacteraemia: a 10-year study in a tertiary-care centre in Mexico City. J Glob Antimicrob Resist 2021; 24:198–204 [View Article] [PubMed]
    [Google Scholar]
  30. Rottier WC, Pinholt M, van der Bij AK, Arpi M, Blank SN et al. Attributable mortality of vancomycin resistance in ampicillin-resistant Enterococcus faecium bacteremia in Denmark and the Netherlands: a matched cohort study. Infect Control Hosp Epidemiol 2022; 43:719–727 [View Article] [PubMed]
    [Google Scholar]
  31. Higgs C, Sherry NL, Seemann T, Horan K, Walpola H et al. Optimising genomic approaches for identifying vancomycin-resistant Enterococcus faecium transmission in healthcare settings. Nat Commun 2022; 13:509 [View Article] [PubMed]
    [Google Scholar]
  32. Kirkwood BR. Essentials of Medical Statistics Hoboken, NJ: Wiley-Blackwell; 1988
    [Google Scholar]
  33. Belloso Daza MV, Cortimiglia C, Bassi D, Cocconcelli PS. Genome-based studies indicate that the Enterococcus faecium clade B strains belong to Enterococcus lactis species and lack of the hospital infection associated markers. Int J Syst Evol Microbiol 2021; 71:004948 [View Article] [PubMed]
    [Google Scholar]
  34. Kampmeier S, Tönnies H, Correa-Martinez CL, Mellmann A, Schwierzeck V. A nosocomial cluster of vancomycin resistant enterococci among COVID-19 patients in an intensive care unit. Antimicrob Resist Infect Control 2020; 9:154 [View Article] [PubMed]
    [Google Scholar]
  35. Turner KME, Hanage WP, Fraser C, Connor TR, Spratt BG. Assessing the reliability of eBURST using simulated populations with known ancestry. BMC Microbiol 2007; 7:30 [View Article] [PubMed]
    [Google Scholar]
  36. Hughes A, Ballard S, Sullivan S, Marshall C. An outbreak of vanA vancomycin-resistant Enterococcus faecium in a hospital with endemic vanB VRE. Infect Dis Health 2019; 24:82–91 [View Article]
    [Google Scholar]
  37. Gorrie C, Higgs C, Carter G, Stinear TP, Howden B. Genomics of vancomycin-resistant Enterococcus faecium. Microb Genom 2019; 5:e000283 [View Article] [PubMed]
    [Google Scholar]
  38. Leigh RJ, McKenna C, McWade R, Lynch B, Walsh F. Comparative genomics and pangenomics of vancomycin-resistant and susceptible Enterococcus faecium from Irish hospitals. J Med Microbiol 2022; 71:001590 [View Article] [PubMed]
    [Google Scholar]
  39. Pinholt M, Ostergaard C, Arpi M, Bruun NE, Schønheyder HC et al. Incidence, clinical characteristics and 30-day mortality of enterococcal bacteraemia in Denmark 2006-2009: a population-based cohort study. Clin Microbiol Infect 2014; 20:145–151 [View Article] [PubMed]
    [Google Scholar]
  40. Heybati K, Seeger R, Thyagu S, Piticaru J, Ahluwalia N et al. Catheter management across patients with hematologic malignancies and catheter-related blood stream infections: a systematic review. Ann Hematol 2022; 101:2515–2524 [View Article] [PubMed]
    [Google Scholar]
  41. Austin ED, Sullivan SS, Macesic N, Mehta M, Miko BA et al. Reduced mortality of Staphylococcus aureus bacteremia in a retrospective cohort study of 2139 patients: 2007–2015. Clin Infect Dis 2020; 70:1666–1674 [View Article] [PubMed]
    [Google Scholar]
  42. Feldman SF, Temkin E, Wullfhart L, Nutman A, Schechner V et al. A nationwide population-based study of Escherichia coli bloodstream infections: incidence, antimicrobial resistance and mortality. Clin Microbiol Infect 2022; 28:879 [View Article] [PubMed]
    [Google Scholar]
  43. Nørgaard M, Larsson H, Pedersen G, Schønheyder HC, Sørensen HT. Haematological malignancies – a predictor of a poor outcome in patients with bacteraemia. J Infect 2006; 53:190–198 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001731
Loading
/content/journal/jmm/10.1099/jmm.0.001731
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error