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Whole-genome sequencing surveillance of vancomycin-resistant Enterococcus faecium (VRE) detects hospital outbreaks and identifies the postanesthesia care unit as a transmission locus

Published online by Cambridge University Press:  03 June 2025

Sarah M. Schrader ,
Meghan A. Baker ,
Chanu Rhee ,
Michael Klompas ,
Samantha Taffner ,
Zachary Pearson ,
Jay Worley ,
Lynn Bry ,
Sanjat Kanjilal  and
Manfred Brigl
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Sarah M. Schrader
Affiliation:
Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
Meghan A. Baker
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Chanu Rhee
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Michael Klompas
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Samantha Taffner
Affiliation:
Mass General Brigham, Boston, MA, USA
Zachary Pearson
Affiliation:
Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA
Jay Worley
Affiliation:
Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA
Lynn Bry
Affiliation:
Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA Massachusetts Host-Microbiome Center, Brigham and Women’s Hospital, Boston, MA, USA
Sanjat Kanjilal
Affiliation:
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
Manfred Brigl
Affiliation:
Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA
Nicole D. Pecora*
Affiliation:
Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA
*
Corresponding author: Nicole D. Pecora; Email: npecora@bwh.harvard.edu
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Abstract

Objective:

Vancomycin-resistant enterococci (VRE) can cause serious healthcare-associated infections. Patients can become colonized and infected through contact with healthcare workers, hospital surfaces, equipment, and other patients. We evaluated the utility of broadly applied whole-genome sequencing (WGS) surveillance of vancomycin-resistant Enterococcus faecium (VREfm) for detection of hospital-based transmission.

Design:

Retrospective genomic and epidemiologic analysis of clinical VREfm isolates

Setting:

Brigham and Women’s Hospital, an 800-bed tertiary care center in Boston, MA, USA

Methods:

VREfm was isolated from patient screening and diagnostic specimens. We sequenced the genomes of 156 VREfm isolates, 12 at the request of infection control and 144 as a convenience sample, and used single nucleotide polymorphism (SNP) differences to assess relatedness. For isolate pairs separated by 15 or fewer SNPs by two orthogonal comparison methods, we mapped epidemiologic connections to identify putative transmission clusters.

Results:

We found evidence for 16 putative transmission clusters comprising between two and four isolates each and involving 41/156 isolates (26.3%). Our analysis discovered 14 clusters that were missed by traditional surveillance methods and additional members of two clusters that were detected by traditional methods. Patients in four transmission clusters were linked only by exposure to the postanesthesia care unit.

Conclusions:

We show that WGS surveillance for VREfm can support infection control investigations and detect transmission events missed by routine surveillance methods. We identify the postanesthesia care unit as a locus for VREfm transmission, which demonstrates how WGS surveillance could inform targeted interventions to prevent the spread of VREfm.

Information

Type
Original Article
Information
Infection Control & Hospital Epidemiology , Volume 46 , Issue 8 , August 2025 , pp. 797 - 804
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Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

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References

CDC. Vancomycin-resistant Enterococci (VRE) Basics. Vancomycin-resistant Enterococci (VRE). June 28, 2024. Accessed August 28, 2024. https://www.cdc.gov/vre/about/index.html Google Scholar
Puchter, L, Chaberny, IF, Schwab, F, Vonberg, RP, Bange, FC, Ebadi, E. Economic burden of nosocomial infections caused by vancomycin-resistant enterococci. Antimicrob Resist Infect Control 2018;7:1. doi: 10.1186/s13756-017-0291-z CrossRefGoogle ScholarPubMed
Prematunge, C, MacDougall, C, Johnstone, J, 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. doi: 10.1017/ice.2015.228 CrossRefGoogle ScholarPubMed
Meschiari, M, Kaleci, S, Monte, MD, et al. Vancomycin resistant enterococcus risk factors for hospital colonization in hematological patients: a matched case-control study. Antimicrob Resist Infect Control 2023;12:126. doi: 10.1186/s13756-023-01332-x CrossRefGoogle ScholarPubMed
Alevizakos, M, Gaitanidis, A, Nasioudis, D, Tori, K, Flokas, ME, Mylonakis, E. Colonization with vancomycin-resistant enterococci and risk for bloodstream infection among patients with malignancy: a systematic review and meta-analysis. Open Forum Infect Dis 2017;4:ofw246. doi: 10.1093/ofid/ofw246 CrossRefGoogle ScholarPubMed
Arias, CA, Murray, BE. The rise of the Enterococcus: beyond vancomycin resistance. Nat Rev Microbiol 2012;10:266–278. doi: 10.1038/nrmicro2761 CrossRefGoogle ScholarPubMed
Wendt, C, Wiesenthal, B, Dietz, E, Rüden, H. Survival of vancomycin-resistant and vancomycin-susceptible enterococci on dry surfaces. J Clin Microbiol 1998;36:3734–3736.CrossRefGoogle ScholarPubMed
Neely, AN, Maley, MP. Survival of enterococci and staphylococci on hospital fabrics and plastic. J Clin Microbiol. 2000;38:724–726.CrossRefGoogle ScholarPubMed
Porter, L, Sultan, O, Mitchell, BG, et al. How long do nosocomial pathogens persist on inanimate surfaces? A scoping review. J Hosp Infect 2024;147:25–31. doi: 10.1016/j.jhin.2024.01.023 CrossRefGoogle Scholar
Byers, KE, Durbin, LJ, Simonton, BM, Anglim, AM, Adal, KA, Farr, BM. Disinfection of hospital rooms contaminated with vancomycin-resistant Enterococcus faecium. Infect Control Hosp Epidemiol 1998;19:261–264. doi: 10.1086/647806 Google ScholarPubMed
Tan, C, Linkenheld-Struk, A, Williams, V, et al. The role of the environment in transmission of vancomycin-resistant Enterococcus: a proof-of-concept study. Antimicrob Steward Healthc Epidemiol 2022;2:e178. doi: 10.1017/ash.2022.318 CrossRefGoogle ScholarPubMed
Permana, B, Harris, PNA, Runnegar, N, et al. Using genomics to investigate an outbreak of vancomycin-resistant Enterococcus faecium ST78 at a large tertiary hospital in Queensland. Microbiol Spectr 2023;11:e0420422. doi: 10.1128/spectrum.04204-22 CrossRefGoogle Scholar
Abdelbary, MHH, Senn, L, Greub, G, Chaillou, G, Moulin, E, Blanc, DS. Whole-genome sequencing revealed independent emergence of vancomycin-resistant Enterococcus faecium causing sequential outbreaks over 3 years in a tertiary care hospital. Eur J Clin Microbiol Infect Dis 2019;38:1163–1170. doi: 10.1007/s10096-019-03524-z CrossRefGoogle ScholarPubMed
Sherry, NL, Gorrie, CL, Kwong, JC, et al. Multi-site implementation of whole genome sequencing for hospital infection control: a prospective genomic epidemiological analysis. Lancet Reg Health West Pac 2022;23:100446. doi: 10.1016/j.lanwpc.2022.100446 Google ScholarPubMed
Pinholt, M, Larner-Svensson, H, Littauer, P, et al. Multiple hospital outbreaks of vanA Enterococcus faecium in Denmark, 2012-13, investigated by WGS, MLST and PFGE. J Antimicrob Chemother 2015;70:2474–2482. doi: 10.1093/jac/dkv142 CrossRefGoogle ScholarPubMed
Brodrick, HJ, Raven, KE, Harrison, EM, et al. Whole-genome sequencing reveals transmission of vancomycin-resistant Enterococcus faecium in a healthcare network. Genome Med 2016;8:4. doi: 10.1186/s13073-015-0259-7 CrossRefGoogle Scholar
Ward, DV, Hoss, AG, Kolde, R, et al. Integration of genomic and clinical data augments surveillance of healthcare-acquired infections. Infect Control Hosp Epidemiol 2019;40:649–655. doi: 10.1017/ice.2019.75 CrossRefGoogle Scholar
Eichel, V, Klein, S, Bootsveld, C, et al. Challenges in interpretation of WGS and epidemiological data to investigate nosocomial transmission of vancomycin-resistant Enterococcus faecium in an endemic region: incorporation of patient movement network and admission screening. J Antimicrob Chemother 2020;75:1716–1721. doi: 10.1093/jac/dkaa122 CrossRefGoogle Scholar
Sundermann, AJ, Srinivasa, VR, Mills, EG, et al. Genomic sequencing surveillance of patients colonized with vancomycin-resistant Enterococcus (VRE) improves detection of hospital-associated transmission. medRxiv 2024.05.01.24306710; https://doi.org/10.1101/2024.05.01.24306710 CrossRefGoogle Scholar
Sundermann, AJ, Babiker, A, Marsh, JW, et al. Outbreak of vancomycin-resistant Enterococcus faecium in interventional radiology: detection through whole-genome sequencing-based surveillance. Clin Infect Dis 2020;70:2336–2343. doi: 10.1093/cid/ciz666 CrossRefGoogle ScholarPubMed
Gouliouris, T, Coll, F, Ludden, C, et al. Quantifying acquisition and transmission of Enterococcus faecium using genomic surveillance. Nat Microbiol 2021;6:103–111. doi: 10.1038/s41564-020-00806-7 CrossRefGoogle ScholarPubMed
Higgs, C, Sherry, NL, Seemann, T, et al. Optimising genomic approaches for identifying vancomycin-resistantEnterococcus faecium transmission in healthcare settings. Nat Commun 2022;13:509. doi: 10.1038/s41467-022-28156-4 CrossRefGoogle Scholar
Bolger, AM, Lohse, M, Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014;30:2114–2120. doi: 10.1093/bioinformatics/btu170 CrossRefGoogle ScholarPubMed
Bankevich, A, Nurk, S, Antipov, D, et al. SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012;19:455–477. doi: 10.1089/cmb.2012.0021 CrossRefGoogle ScholarPubMed
Gurevich, A, Saveliev, V, Vyahhi, N, Tesler, G. QUAST: quality assessment tool for genome assemblies. Bioinformatics 2013;29:1072–1075. doi: 10.1093/bioinformatics/btt086 CrossRefGoogle ScholarPubMed
Roosaare, M, Vaher, M, Kaplinski, L, et al. StrainSeeker: fast identification of bacterial strains from raw sequencing reads using user-provided guide trees. PeerJ 2017;5:e3353. doi: 10.7717/peerj.3353 CrossRefGoogle ScholarPubMed
Gupta, A, Jordan, IK, Rishishwar, L. stringMLST: a fast k-mer based tool for multilocus sequence typing. Bioinformatics 2017;33:119–121. doi: 10.1093/bioinformatics/btw586 CrossRefGoogle ScholarPubMed
Davis, S, Pettengill, JB, Luo, Y, et al. CFSAN SNP pipeline: an automated method for constructing SNP matrices from next-generation sequence data. PeerJ Comput Sci 2015;1:e20. doi: 10.7717/peerj-cs.20 CrossRefGoogle Scholar
Harris, SR. SKA: Split kmer analysis toolkit for bacterial genomic epidemiology. bioRxiv 453142; doi: https://doi.org/10.1101/453142 CrossRefGoogle Scholar
Badgwell, JM. The postanesthesia care unit: a high-risk environment for bloodborne and infectious respiratory pathogens. J Post Anesth Nurs 1996;11:66–70. doi: 10.1016/s1089-9472(06)80004-3 Google ScholarPubMed
Miller, JK, Chen, J, Sundermann, A, et al. Statistical outbreak detection by joining medical records and pathogen similarity. J Biomed Inform 2019;91:103126. doi: 10.1016/j.jbi.2019.103126 CrossRefGoogle ScholarPubMed
Kanjilal, S. The modern alchemy of clinical pathology: turning the output of microbiology laboratory operations into gold. J Clin Microbiol 2024;62:e01709–22. doi: 10.1128/jcm.01709-22 CrossRefGoogle Scholar
Pecora, N, Holzbauer, S, Wang, X, et al. Genomic analysis of Clostridioides difficile in 2 regions of the United States reveals a diversity of strains and limited transmission. J Infect Dis 2022;225:121–129. doi: 10.1093/infdis/jiab294 CrossRefGoogle ScholarPubMed
Maechler, F, Weber, A, Schwengers, O, et al. Split k-mer analysis compared to cgMLST and SNP-based core genome analysis for detecting transmission of vancomycin-resistant enterococci: results from routine outbreak analyses across different hospitals and hospitals networks in Berlin, Germany. Microbial Genomics 2023;9:000937. doi: 10.1099/mgen.0.000937 CrossRefGoogle ScholarPubMed
Kumar, P, Sundermann, AJ, Martin, EM, et al. Method for economic evaluation of bacterial whole genome sequencing surveillance compared to standard of care in detecting hospital outbreaks. Clin Infect Dis 2021;73:e9–e18. doi: 10.1093/cid/ciaa512 CrossRefGoogle ScholarPubMed
Lloyd-Smith, P, Younger, J, Lloyd-Smith, E, Green, H, Leung, V, Romney, MG. Economic analysis of vancomycin-resistant enterococci at a Canadian hospital: assessing attributable cost and length of stay. J Hosp Infect 2013;85:54–59. doi: 10.1016/j.jhin.2013.06.016 CrossRefGoogle Scholar
Price, V, Ngwira, LG, Lewis, JM, et al. A systematic review of economic evaluations of whole-genome sequencing for the surveillance of bacterial pathogens. Microb Genom 2023;9:mgen000947. doi: 10.1099/mgen.0.000947 Google ScholarPubMed
Gordon, LG, Elliott, TM, Forde, B, et al. Budget impact analysis of routinely using whole-genomic sequencing of six multidrug-resistant bacterial pathogens in Queensland, Australia. BMJ Open 2021;11:e041968. doi: 10.1136/bmjopen-2020-041968 CrossRefGoogle ScholarPubMed
Mellmann, A, Bletz, S, Böking, T, et al. Real-time genome sequencing of resistant bacteria provides precision infection control in an institutional setting. J Clin Microbiol 2016;54:2874–2881. doi: 10.1128/jcm.00790-16 CrossRefGoogle Scholar
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