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Abstract

Background

Vancomycin-resistant enterococci (VRE) are increasing in Denmark and Europe. Linezolid and vancomycin-resistant enterococci (LVRE) are of concern, as treatment options are limited. Vancomycin-variable enterococci (VVE) harbour the gene complex but are phenotypically vancomycin-susceptible.

Aim

The aim was to describe clonal shifts for VRE and VVE in Denmark between 2015 and 2022 and to investigate genotypic linezolid resistance among the VRE and VVE.

Methods

From 2015 to 2022, 4,090 Danish clinical VRE and VVE isolates were whole genome sequenced. We extracted vancomycin resistance genes and sequence types (STs) from the sequencing data and performed core genome multilocus sequence typing (cgMLST) analysis for . All isolates were tested for the presence of mutations or genes encoding linezolid resistance.

Results

In total 99% of the VRE and VVE isolates were From 2015 through 2019, 91.1% of the VRE and VVE were . During 2020, to the number of increased to 254 of 509 VRE and VVE isolates. Between 2015 and 2022, seven clusters dominated: ST80-CT14 , ST117-CT24 , ST203-CT859 ST1421-CT1134 (VVE cluster) ST80-CT1064 , ST117-CT36 and ST80-CT2406 We detected 35 linezolid vancomycin-resistant and eight linezolid-resistant VVEfm.

Conclusion

From 2015 to 2022, the numbers of VRE and VVE increased. The spread of the VVE cluster ST1421-CT1134 in Denmark is a concern, especially since VVE diagnostics are challenging. The finding of LVRE, although in small numbers, ia also a concern, as treatment options are limited.

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2024-06-06
2024-11-21
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References

  1. Pfaller MA, Cormican M, Flamm RK, Mendes RE, Jones RN. Temporal and geographic variation in antimicrobial susceptibility and resistance patterns of enterococci: results from the SENTRY antimicrobial surveillance program, 1997-2016. Open Forum Infect Dis. 2019;6(Suppl 1):S54-62.  https://doi.org/10.1093/ofid/ofy344  PMID: 30895215 
  2. Cavallazzi Sebold B, Li J, Ni G, Fu Q, Li H, Liu X, et al. Going beyond host defence peptides: horizons of chemically engineered peptides for multidrug-resistant bacteria. BioDrugs. 2023;37(5):607-23.  https://doi.org/10.1007/s40259-023-00608-3  PMID: 37300748 
  3. Kristich CJ, Rice LB, Arias CA. Enterococcal infection—treatment and antibiotic resistance. In: Gilmore MS, Clewell DB, Ike Y, et al, editors. Enterococci: From commensals to leading causes of drug resistant infection. Boston: Massachusetts Eye and Ear Infirmary; 2014. Available from: https://www.ncbi.nlm.nih.gov/books/NBK190420
  4. Hollenbeck BL, Rice LB. Intrinsic and acquired resistance mechanisms in enterococcus. Virulence. 2012;3(5):421-33.  https://doi.org/10.4161/viru.21282  PMID: 23076243 
  5. Santajit S, Indrawattana N. Mechanisms of antimicrobial resistance in ESKAPE pathogens. Tulkens PM, editor. Biomed Res Int. 2016;2016:2475067.
  6. European Centre for Disease Prevention and Control (ECDC). Antimicrobial resistance in the EU/EEA (EARS-Net) - Annual epidemiological report for 2021. Stockholm: ECDC; 2022. Available from: https://www.ecdc.europa.eu/en/publications-data/surveillance-antimicrobial-resistance-europe-2021
  7. Lebreton F, Depardieu F, Bourdon N, Fines-Guyon M, Berger P, Camiade S, et al. D-Ala-d-Ser VanN-type transferable vancomycin resistance in Enterococcus faecium. Antimicrob Agents Chemother. 2011;55(10):4606-12.  https://doi.org/10.1128/AAC.00714-11  PMID: 21807981 
  8. Sivertsen A, Pedersen T, Larssen KW, Bergh K, Rønning TG, Radtke A, et al. A silenced vanA gene cluster on a transferable plasmid caused an outbreak of vancomycin-variable enterococci. Antimicrob Agents Chemother. 2016;60(7):4119-27.  https://doi.org/10.1128/AAC.00286-16  PMID: 27139479 
  9. Coccitto SN, Cinthi M, Simoni S, Pocognoli A, Zeni G, Mazzariol A, et al. Genetic analysis of vancomycin-variable Enterococcus faecium clinical isolates in Italy. Eur J Clin Microbiol Infect Dis. 2024;43(4):673-82.  https://doi.org/10.1007/s10096-024-04768-0  PMID: 38296911 
  10. Levitus M, Rewane A, Perera TB. Vancomycin-Resistant Enterococci. Treasure Island: StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513233
  11. Hasman H, Clausen PTLC, Kaya H, Hansen F, Knudsen JD, Wang M, et al. LRE-Finder, a Web tool for detection of the 23S rRNA mutations and the optrA, cfr, cfr(B) and poxtA genes encoding linezolid resistance in enterococci from whole-genome sequences. J Antimicrob Chemother. 2019;74(6):1473-6.  https://doi.org/10.1093/jac/dkz092  PMID: 30863844 
  12. Hammerum AM, Baig S, Kamel Y, Roer L, Pinholt M, Gumpert H, et al. Emergence of vanA Enterococcus faecium in Denmark, 2005-15. J Antimicrob Chemother. 2017;72(8):2184-90.  https://doi.org/10.1093/jac/dkx138  PMID: 28541565 
  13. Hammerum AM, Justesen US, Pinholt M, Roer L, Kaya H, Worning P, 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(34):1900503.  https://doi.org/10.2807/1560-7917.ES.2019.24.34.1900503  PMID: 31456560 
  14. Ribeiro Duarte AS, Attauabi M, Sandberg M, Lindegaard M, Sönksen UW, Andersen VD, et al. DANMAP 2022: Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. Copenhagen: Statens Serum Institut. 2023. Available from: https://www.danmap.org/reports/2022
  15. European Committee on Antimicrobial Susceptibility Testing (EUCAST). Antimicrobial susceptibility testing EUCAST disk diffusion method. Version 12.0. Växjö: EUCAST; 2024. Available from: https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Disk_test_documents/2024_manuals/Manual_v_12.0_EUCAST_Disk_Test_2024.pdf
  16. Voldstedlund M, Haarh M, Mølbak K, MiBa Board of Representatives. The Danish Microbiology Database (MiBa) 2010 to 2013. Euro Surveill. 2014;19(1):20667.
  17. Bager P, Kähler J, Andersson M, Holzknecht BJ, Kjær Hansen SG, Schønning K, et al. Comparison of morbidity and mortality after bloodstream infection with vancomycin-resistant versus -susceptible Enterococcus faecium: a nationwide cohort study in Denmark, 2010-2019. Emerg Microbes Infect. 2024;13(1):2309969.  https://doi.org/10.1080/22221751.2024.2309969  PMID: 38258968 
  18. de Been M, Pinholt M, Top J, Bletz S, Mellmann A, van Schaik W, et al. Core genome multilocus sequence typing scheme for high- resolution typing of Enterococcus faecium. J Clin Microbiol. 2015;53(12):3788-97.  https://doi.org/10.1128/JCM.01946-15  PMID: 26400782 
  19. Werner G, Neumann B, Weber RE, Kresken M, Wendt C, Bender JK, et al. , VRE study group. Thirty years of VRE in Germany - "expect the unexpected": The view from the National Reference Centre for Staphylococci and Enterococci. Drug Resist Updat. 2020;53:100732.  https://doi.org/10.1016/j.drup.2020.100732  PMID: 33189998 
  20. Weber RE, Bender JK, Noll I, Abu Sin M, Eckmanns T, Werner G. Eigenschaften, Häufigkeit und Verbreitung von Vancomycin-resistenten Enterokokken in Deutschland – Update 2019/2020. [Characteristics, frequency and spread of vancomycin-resistant enterococci on Germany – update 2019/2020]. Epid. Bull.2021;27:32-42. German.
  21. Cimen C, Berends MS, Bathoorn E, Lokate M, Voss A, Friedrich AW, et al. Vancomycin-resistant enterococci (VRE) in hospital settings across European borders: a scoping review comparing the epidemiology in the Netherlands and Germany. Antimicrob Resist Infect Control. 2023;12(1):78.  https://doi.org/10.1186/s13756-023-01278-0  PMID: 37568229 
  22. 2022 NORM og NORM-VET: Usage of antimicrobial agents and occurrence of antimicrobial resistance in Norway. Tromsø/Oslo: Folkehelseinstituttet/Veterinærinstituttet; 2023. Available from: https://www.fhi.no/en/publ/2023/norm-og-norm-vet-usage-of-antimicrobial-agents-and-occurrence-of-antimicrobial-resistance-in-norway
  23. Top J, Sinnige JC, Brouwer EC, Werner G, Corander J, Severin JA, et al. Identification of a novel genomic island associated with vanD-type vancomycin resistance in six dutch vancomycin-resistant Enterococcus faecium isolates. Antimicrob Agents Chemother. 2018;62(3):e01793-17.  https://doi.org/10.1128/AAC.01793-17  PMID: 29311068 
  24. Statens Serum Insititut (SSI). Nationale Infektionshygiejniske Retningslinjer. Supplerende om forholdsregler ved infektioner og bærertilstand i sundhedssektoren. [National guidelines for infection control. Additional rules of conduct for infections and carriage in the health sector]. Copenhagen: SSI; 2023. Danish. Available from: https://hygiejne.ssi.dk/NIRsupplerende
  25. Puchter L, Chaberny IF, Schwab F, Vonberg R-P, Bange F-C, Ebadi E. Economic burden of nosocomial infections caused by vancomycin-resistant enterococci. Antimicrob Resist Infect Control. 2018;7(1):1.  https://doi.org/10.1186/s13756-017-0291-z  PMID: 29312658 
  26. Pinholt M, Larner-Svensson H, Littauer P, Moser CE, Pedersen M, Lemming LE, et al. Multiple hospital outbreaks of vanA Enterococcus faecium in Denmark, 2012-13, investigated by WGS, MLST and PFGE. J Antimicrob Chemother. 2015;70(9):2474-82.  https://doi.org/10.1093/jac/dkv142  PMID: 26031466 
  27. Zhou X, Chlebowicz MA, Bathoorn E, Rosema S, Couto N, Lokate M, et al. Elucidating vancomycin-resistant Enterococcus faecium outbreaks: the role of clonal spread and movement of mobile genetic elements. J Antimicrob Chemother. 2018;73(12):3259-67.  https://doi.org/10.1093/jac/dky349  PMID: 30219855 
  28. Egan SA, Kavanagh NL, Shore AC, Mollerup S, Samaniego Castruita JA, O’Connell B, et al. Genomic analysis of 600 vancomycin-resistant Enterococcus faecium reveals a high prevalence of ST80 and spread of similar vanA regions via IS1216E and plasmid transfer in diverse genetic lineages in Ireland. J Antimicrob Chemother. 2022;77(2):320-30.  https://doi.org/10.1093/jac/dkab393  PMID: 34747439 
  29. Leong KWC, Cooley LA, O’Toole RF. Draft genome sequence of new vancomycin-resistant Enterococcus faecium sequence type 1421. Genome Announc. 2018;6(20):e00438-18.  https://doi.org/10.1128/genomeA.00438-18  PMID: 29773638 
  30. Saito N, Kitazawa J, Horiuchi H, Yamamoto T, Kimura M, Inoue F, et al. Interhospital transmission of vancomycin-resistant Enterococcus faecium in Aomori, Japan. Antimicrob Resist Infect Control. 2022;11(1):99.  https://doi.org/10.1186/s13756-022-01136-5  PMID: 35871001 
  31. Kim HM, Chung DR, Cho SY, Huh K, Kang C-I, Peck KR. Emergence of vancomycin-resistant Enterococcus faecium ST1421 lacking the pstS gene in Korea. Eur J Clin Microbiol Infect Dis. 2020;39(7):1349-56.  https://doi.org/10.1007/s10096-020-03853-4  PMID: 32128641 
  32. 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(2):82-91.  https://doi.org/10.1016/j.idh.2018.12.002  PMID: 30638872 
  33. Santona A, Taviani E, Hoang HM, Fiamma M, Deligios M, Ngo TVQ, et al. Emergence of unusual vanA/vanB2 genotype in a highly mutated vanB2-vancomycin-resistant hospital-associated E. faecium background in Vietnam. Int J Antimicrob Agents. 2018;52(5):586-92.  https://doi.org/10.1016/j.ijantimicag.2018.07.006  PMID: 30012442 
  34. Papagiannitsis CC, Malli E, Florou Z, Medvecky M, Sarrou S, Hrabak J, et al. First description in Europe of the emergence of Enterococcus faecium ST117 carrying both vanA and vanB genes, isolated in Greece. J Glob Antimicrob Resist. 2017;11:68-70.  https://doi.org/10.1016/j.jgar.2017.07.010  PMID: 28754459 
  35. Pinholt M, Mollerup S, Boye K, Worning P, Holzknecht BJ, Nygaard S, et al. Investigation of the introduction and dissemination of vanB Enterococcus faecium in the Capital Region of Denmark and development of a rapid and accurate clone-specific vanB E. faecium PCR. J Antimicrob Chemother. 2021;76(9):2260-7.  https://doi.org/10.1093/jac/dkab198  PMID: 34151364 
  36. Weber A, Maechler F, Schwab F, Gastmeier P, Kola A. Increase of vancomycin-resistant Enterococcus faecium strain type ST117 CT71 at Charité - Universitätsmedizin Berlin, 2008 to 2018. Antimicrob Resist Infect Control. 2020;9(1):109.  https://doi.org/10.1186/s13756-020-00754-1  PMID: 32678047 
  37. van Hal SJ, Willems RJL, Gouliouris T, Ballard SA, Coque TM, Hammerum AM, et al. The global dissemination of hospital clones of Enterococcus faecium. Genome Med. 2021;13(1):52.  https://doi.org/10.1186/s13073-021-00868-0  PMID: 33785076 
  38. Roer L, Kaya H, Tedim AP, Novais C, Coque TM, Aarestrup FM, et al. VirulenceFinder for Enterococcus faecium and Enterococcus lactis: an enhanced database for detection of putative virulence markers by using whole-genome sequencing data. Microbiol Spectr. 2024;12(3):e0372423.  https://doi.org/10.1128/spectrum.03724-23  PMID: 38329344 
  39. Lee T, Pang S, Daley DA, Pearson JC, Abraham S, Coombs GW. The changing molecular epidemiology of Enterococcus faecium harbouring the van operon at a teaching hospital in Western Australia: A fifteen-year retrospective study. Int J Med Microbiol. 2022;312(1):151546.  https://doi.org/10.1016/j.ijmm.2021.151546  PMID: 34922099 
  40. Rubin IMC, Pedersen MS, Mollerup S, Kaya H, Petersen AM, Westh H, et al. Association between vancomycin-resistant Enterococcus faecium colonization and subsequent infection: a retrospective WGS study. J Antimicrob Chemother. 2020;75(7):1712-5.  https://doi.org/10.1093/jac/dkaa074  PMID: 32125377 
  41. Azzouz A, Preuss CV. Linezolid. Treasure Island: StatPearls Publishing; 2024. Available from: http://www.ncbi.nlm.nih.gov/books/nbk539793
  42. Heininger A, Zimmermann S, Bootsveld C, Boutin S, Nurjadi D. Low prevalence of combined linezolid- and vancomycin-resistant Enterococcus faecium from hospital admission screening in an endemic region in Germany. J Glob Antimicrob Resist. 2020;22:646-50.  https://doi.org/10.1016/j.jgar.2020.05.003  PMID: 32439568 
  43. Misiakou M-A, Hertz FB, Schønning K, Häussler S, Nielsen KL. Emergence of linezolid-resistant Enterococcus faecium in a tertiary hospital in Copenhagen. Microb Genom. 2023;9(7):mgen001055.  https://doi.org/10.1099/mgen.0.001055  PMID: 37410656 
  44. Olearo F, Both A, Belmar Campos C, Hilgarth H, Klupp E-M, Hansen JL, et al. Emergence of linezolid-resistance in vancomycin-resistant Enterococcus faecium ST117 associated with increased linezolid-consumption. Int J Med Microbiol. 2021;311(2):151477.  https://doi.org/10.1016/j.ijmm.2021.151477  PMID: 33524636 
Surveillance of vancomycin-resistant enterococci reveals shift in dominating clusters from vanA to vanB Enterococcus faecium clusters, Denmark, 2015 to 2022
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Anette+M+Hammerum&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Hammerum Anette M</a>, <a href="/search?value1=Kasper+Thystrup+Karstensen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Karstensen Kasper Thystrup</a>, <a href="/search?value1=Louise+Roer&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Roer Louise</a>, <a href="/search?value1=H%C3%BClya+Kaya&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Kaya Hülya</a>, <a href="/search?value1=Mikkel+Lindegaard&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Lindegaard Mikkel</a>, <a href="/search?value1=Lone+Jannok+Porsbo&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Porsbo Lone Jannok</a>, <a href="/search?value1=Anne+Kjerulf&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Kjerulf Anne</a>, <a href="/search?value1=Mette+Pinholt&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Pinholt Mette</a>, <a href="/search?value1=Barbara+Juliane+Holzknecht&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Holzknecht Barbara Juliane</a>, <a href="/search?value1=Peder+Worning&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Worning Peder</a>, <a href="/search?value1=Karen+Leth+Nielsen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Nielsen Karen Leth</a>, <a href="/search?value1=Sanne+Gr%C3%B8nvall+Kj%C3%A6r+Hansen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Hansen Sanne Grønvall Kjær</a>, <a href="/search?value1=Marianne+Clausen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Clausen Marianne</a>, <a href="/search?value1=Turid+S+S%C3%B8ndergaard&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Søndergaard Turid S</a>, <a href="/search?value1=Esad+Dzajic&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Dzajic Esad</a>, <a href="/search?value1=Claus+%C3%98stergaard&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Østergaard Claus</a>, <a href="/search?value1=Mikala+Wang&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Wang Mikala</a>, <a href="/search?value1=Kristoffer+Koch&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Koch Kristoffer</a>, <a href="/search?value1=Henrik+Hasman&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Hasman Henrik</a></span>. Surveillance of vancomycin-resistant enterococci reveals shift in dominating clusters from vanA to vanB Enterococcus faecium clusters, Denmark, 2015 to 2022. <a href="/content/ecdc">Euro Surveill.</a> 2024;29(23):pii=2300633. <a href="https://doi.org/10.2807/1560-7917.ES.2024.29.23.2300633" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2024.29.23.2300633</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 15 Nov 2023;&nbsp;&nbsp; <span class="generated">Accepted</span>: 26 Mar 2024 </span> </p>
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