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Mandatory reporting of methicillin-resistant (MRSA) bloodstream infections (BSI) has occurred in England for over 15years. Epidemiological information is recorded, but routine collection of isolates for characterisation has not been routinely undertaken. Ongoing developments in whole-genome sequencing (WGS) have demonstrated its value in outbreak investigations and for determining the spread of antimicrobial resistance and bacterial population structure. Benefits of adding genomics to routine epidemiological MRSA surveillance are unknown.


To determine feasibility and potential utility of adding genomics to epidemiological surveillance of MRSA.


We conducted an epidemiological and genomic survey of MRSA BSI in England over a 1-year period (1 October 2012­–30 September 2013).


During the study period, 903 cases of MRSA BSI were reported; 425 isolates were available for sequencing of which, 276 (65%) were clonal complex (CC) 22. Addition of 64 MRSA genomes from published outbreak investigations showed that the study genomes could provide context for outbreak isolates and supported cluster identification. Comparison to other MRSA genome collections demonstrated variation in clonal diversity achieved through different sampling strategies and identified potentially high-risk clones e.g. USA300 and local expansion of CC5 MRSA in South West England.


We demonstrate the potential utility of combined epidemiological and genomic MRSA BSI surveillance to determine the national population structure of MRSA, contextualise previous MRSA outbreaks, and detect potentially high-risk lineages. These findings support the integration of epidemiological and genomic surveillance for MRSA BSI as a step towards a comprehensive surveillance programme in England.


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  1. Duerden B, Fry C, Johnson AP, Wilcox MH. The Control of Methicillin-Resistant Staphylococcus aureus Blood Stream Infections in England. Open Forum Infect Dis. 2015;2(2):ofv035.  https://doi.org/10.1093/ofid/ofv035  PMID: 26380336 
  2. Johnson AP, Davies J, Guy R, Abernethy J, Sheridan E, Pearson A, et al. Mandatory surveillance of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in England: the first 10 years. J Antimicrob Chemother. 2012;67(4):802-9.  https://doi.org/10.1093/jac/dkr561  PMID: 22223229 
  3. Coia JE, Duckworth GJ, Edwards DI, Farrington M, Fry C, Humphreys H, et al. Joint Working Party of the British Society of Antimicrobial ChemotherapyHospital Infection SocietyInfection Control Nurses Association. Guidelines for the control and prevention of meticillin-resistant Staphylococcus aureus (MRSA) in healthcare facilities. J Hosp Infect. 2006;63(Suppl 1):S1-44.  https://doi.org/10.1016/j.jhin.2006.01.001  PMID: 16581155 
  4. Wilson M. Addressing the problems of long-term urethral catheterization: Part 1. Br J Nurs. 2011;20(22):1418-20.  https://doi.org/10.12968/bjon.2011.20.22.1418  PMID: 22241489 
  5. Wyllie D, Paul J, Crook D. Waves of trouble: MRSA strain dynamics and assessment of the impact of infection control. J Antimicrob Chemother. 2011;66(12):2685-8.  https://doi.org/10.1093/jac/dkr392  PMID: 21948966 
  6. Lawes T, López-Lozano JM, Nebot C, Macartney G, Subbarao-Sharma R, Dare CR, et al. Turning the tide or riding the waves? Impacts of antibiotic stewardship and infection control on MRSA strain dynamics in a Scottish region over 16 years: non-linear time series analysis. BMJ Open. 2015;5(3):e006596.  https://doi.org/10.1136/bmjopen-2014-006596  PMID: 25814495 
  7. Price JR, Didelot X, Crook DW, Llewelyn MJ, Paul J. Whole genome sequencing in the prevention and control of Staphylococcus aureus infection. J Hosp Infect. 2013;83(1):14-21.  https://doi.org/10.1016/j.jhin.2012.10.003  PMID: 23164609 
  8. Garvey MI, Pichon B, Bradley CW, Moiemen NS, Oppenheim B, Kearns AM. Improved understanding of an outbreak of meticillin-resistant Staphylococcus aureus in a regional burns centre via whole-genome sequencing. J Hosp Infect. 2016;94(4):401-4.  https://doi.org/10.1016/j.jhin.2016.09.013  PMID: 27729168 
  9. Harris SR, Cartwright EJ, Török ME, Holden MT, Brown NM, Ogilvy-Stuart AL, et al. Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study. Lancet Infect Dis. 2013;13(2):130-6.  https://doi.org/10.1016/S1473-3099(12)70268-2  PMID: 23158674 
  10. Köser CU, Holden MT, Ellington MJ, Cartwright EJ, Brown NM, Ogilvy-Stuart AL, et al. Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N Engl J Med. 2012;366(24):2267-75.  https://doi.org/10.1056/NEJMoa1109910  PMID: 22693998 
  11. Price JR, Golubchik T, Cole K, Wilson DJ, Crook DW, Thwaites GE, et al. Whole-genome sequencing shows that patient-to-patient transmission rarely accounts for acquisition of Staphylococcus aureus in an intensive care unit. Clin Infect Dis. 2014;58(5):609-18.  https://doi.org/10.1093/cid/cit807  PMID: 24336829 
  12. Török ME, Harris SR, Cartwright EJ, Raven KE, Brown NM, Allison ME, et al. Zero tolerance for healthcare-associated MRSA bacteraemia: is it realistic? J Antimicrob Chemother. 2014;69(8):2238-45.  https://doi.org/10.1093/jac/dku128  PMID: 24788657 
  13. Reuter S, Török ME, Holden MTG, Reynolds R, Raven KE, Blane B, et al. Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland. Genome Res. 2016;26(2):263-70.  https://doi.org/10.1101/gr.196709.115  PMID: 26672018 
  14. Holden MT, Hsu LY, Kurt K, Weinert LA, Mather AE, Harris SR, et al. A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic. Genome Res. 2013;23(4):653-64.  https://doi.org/10.1101/gr.147710.112  PMID: 23299977 
  15. Grundmann H, Schouls LM, Aanensen DM, Pluister GN, Tami A, Chlebowicz M, et al. ESCMID Study Group on Molecular Epidemiological MarkersEuropean Staphylococcal Reference Laboratory Working Group. The dynamic changes of dominant clones of Staphylococcus aureus causing bloodstream infections in the European region: results of a second structured survey. Euro Surveill. 2014;19(49):20987.  https://doi.org/10.2807/1560-7917.ES2014.19.49.20987  PMID: 25523972 
  16. Planet PJ. Life After USA300: The Rise and Fall of a Superbug. J Infect Dis. 2017;215(suppl_1):S71-S77.
  17. Holmes A, Ganner M, McGuane S, Pitt TL, Cookson BD, Kearns AM. Staphylococcus aureus isolates carrying Panton-Valentine leucocidin genes in England and Wales: frequency, characterization, and association with clinical disease. J Clin Microbiol. 2005;43(5):2384-90.  https://doi.org/10.1128/JCM.43.5.2384-2390.2005  PMID: 15872271 
  18. Pichon B, Hill R, Laurent F, Larsen AR, Skov RL, Holmes M, et al. Development of a real-time quadruplex PCR assay for simultaneous detection of nuc, Panton-Valentine leucocidin (PVL), mecA and homologue mecALGA251. J Antimicrob Chemother. 2012;67(10):2338-41.  https://doi.org/10.1093/jac/dks221  PMID: 22687894 
  19. Reuter S, Ellington MJ, Cartwright EJ, Köser CU, Török ME, Gouliouris T, et al. Rapid bacterial whole-genome sequencing to enhance diagnostic and public health microbiology. JAMA Intern Med. 2013;173(15):1397-404.  https://doi.org/10.1001/jamainternmed.2013.7734  PMID: 23857503 
  20. Page AJ, De Silva N, Hunt M, Quail MA, Parkhill J, Harris SR, et al. Robust high-throughput prokaryote de novo assembly and improvement pipeline for Illumina data. Microb Genom. 2016;2(8):e000083.  https://doi.org/10.1099/mgen.0.000083  PMID: 28348874 
  21. Page AJ, Taylor B, Keane JA. Multilocus sequence typing by blast from de novo assemblies against PubMLST. The journal of Open Source Software. 2016;8(1):118.  https://doi.org/10.21105/joss.00118 
  22. Stamatakis A, Ludwig T, Meier H. RAxML-III: a fast program for maximum likelihood-based inference of large phylogenetic trees. Bioinformatics. 2005;21(4):456-63.  https://doi.org/10.1093/bioinformatics/bti191  PMID: 15608047 
  23. Kahl BC, Mellmann A, Deiwick S, Peters G, Harmsen D. Variation of the polymorphic region X of the protein A gene during persistent airway infection of cystic fibrosis patients reflects two independent mechanisms of genetic change in Staphylococcus aureus. J Clin Microbiol. 2005;43(1):502-5.  https://doi.org/10.1128/JCM.43.1.502-505.2005  PMID: 15635028 
  24. Coll F, Harrison EM, Toleman MS, Reuter S, Raven KE, Blane B, et al. Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community. Sci Transl Med. 2017;9(413):eaak9745.  PMID: 29070701 
  25. Uhlemann A-C, Dordel J, Knox JR, Raven KE, Parkhill J, Holden MTG, et al. Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community. Proc Natl Acad Sci USA. 2014;111(18):6738-43.  https://doi.org/10.1073/pnas.1401006111  PMID: 24753569 
  26. David MZ, Daum RS. Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev. 2010;23(3):616-87.  https://doi.org/10.1128/CMR.00081-09  PMID: 20610826 
  27. Centers for Disease Control and Prevention (CDC). Methicillin-resistant Staphylococcus aureus skin or soft tissue infections in a state prison--Mississippi, 2000. MMWR Morb Mortal Wkly Rep. 2001;50(42):919-22. PMID: 11699844 
  28. Seidl K, Leimer N, Palheiros Marques M, Furrer A, Senn G, Holzmann-Bürgel A, et al. USA300 methicillin-resistant Staphylococcus aureus in Zurich, Switzerland between 2001 and 2013. Int J Med Microbiol. 2014;304(8):1118-22.  https://doi.org/10.1016/j.ijmm.2014.08.005  PMID: 25200859 
  29. Baud O, Giron S, Aumeran C, Mouly D, Bardon G, Besson M, et al. First outbreak of community-acquired MRSA USA300 in France: failure to suppress prolonged MRSA carriage despite decontamination procedures. Eur J Clin Microbiol Infect Dis. 2014;33(10):1757-62.  https://doi.org/10.1007/s10096-014-2127-6  PMID: 24816900 
  30. Blanco R, Tristan A, Ezpeleta G, Larsen AR, Bes M, Etienne J, et al. Molecular epidemiology of Panton-Valentine leukocidin-positive Staphylococcus aureus in Spain: emergence of the USA300 clone in an autochthonous population. J Clin Microbiol. 2011;49(1):433-6.  https://doi.org/10.1128/JCM.02201-10  PMID: 21068288 
  31. van der Mee-Marquet N, Poisson DM, Lavigne JP, Francia T, Tristan A, Vandenesch F, et al. The incidence of Staphylococcus aureus ST8-USA300 among French pediatric inpatients is rising. Eur J Clin Microbiol Infect Dis. 2015;34(5):935-42.  https://doi.org/10.1007/s10096-014-2308-3  PMID: 25575950 
  32. Toleman MS, Reuter S, Coll F, Harrison EM, Blane B, Brown NM, et al. Systematic Surveillance Detects Multiple Silent Introductions and Household Transmission of Methicillin-Resistant Staphylococcus aureus USA300 in the East of England. J Infect Dis. 2016;214(3):447-53.  https://doi.org/10.1093/infdis/jiw166  PMID: 27122590 
  33. Bartels MD, Petersen A, Worning P, Nielsen JB, Larner-Svensson H, Johansen HK, et al. Comparing whole-genome sequencing with Sanger sequencing for spa typing of methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2014;52(12):4305-8.  https://doi.org/10.1128/JCM.01979-14  PMID: 25297335 
  34. Bletz S, Mellmann A, Rothgänger J, Harmsen D. Ensuring backwards compatibility: traditional genotyping efforts in the era of whole genome sequencing. Clin Microbiol Infect. 2015;21(4):347.e1-4.  https://doi.org/10.1016/j.cmi.2014.11.005  PMID: 25658529 
  35. Argimón S, Abudahab K, Goater RJ, Fedosejev A, Bhai J, Glasner C, et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb Genom. 2016;2(11):e000093.  https://doi.org/10.1099/mgen.0.000093  PMID: 28348833 
  36. Jolley KA, Maiden MC. BIGSdb: Scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics. 2010;11(1):595.  https://doi.org/10.1186/1471-2105-11-595  PMID: 21143983 
  37. Packer STS, Buunaaisie C, Neale J, Hopewell-Kelly N, Telfer M, Williams OM, et al. A prevalence survey investigating factors associated with MRSA colonisation in people who inject drugs in Bristol, UK. Poster presentation at Research and Applied Epidemiology Scientific Conference; 2017 Mar 21 Warwick University, Coventry, UK.

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