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Clostridium difficile infections in Finland, 2008–2015: trends, diagnostics and ribotypes

  • S. MentulaEmail author
  • S. M. Kotila
  • O. Lyytikäinen
  • S. Ibrahem
  • J. Ollgren
  • A. Virolainen
Original Article

Abstract

We evaluated Clostridium difficile (CD) diagnostics in Finnish clinical microbiology laboratories during 2006–2011, with an update in 2015, in relation to CD surveillance data of the National Infectious Disease Register (NIDR) and ribotyping data from the national reference laboratory during the years 2008–2015. In 2011, diagnostic activity varied regionally more than three-fold and the positivity rate ranged between 7 and 21%. Nucleic acid amplification testing (NAAT) was implemented in the regions with high activity and NAAT users tested 30% more patients and found 15% more cases per population than those not using it. Culture was performed in 79% of laboratories, primary toxin testing by enzyme immunoassay (EIA) in 83% and by NAAT in 17%. In 2014, 12/19 laboratories used NAAT as the primary detection method and four as the secondary method, and ten cultured. Increasing usage of NAAT was not systematically related to various trends detected regionally in annual CD rates. Polymerase chain reaction (PCR) ribotyping of 1771 CD isolates (4.1% of CD cases) identified 146 distinct profiles, of which 37% were binary toxin positive. The most common ribotype was 027, but its proportion decreased, while 078 slightly increased. Transition from culture to NAAT in CD infection (CDI) diagnostics did not cause a significant increase in the observed CDI incidence. Major differences between diagnostic activity, methods and strategies in different regions have persisted over the years, which should be considered when comparing the regional epidemiology of CDI.

Notes

Acknowledgements

Arja Kanervo-Nordström and Anne Bryk are acknowledged for their technical assistance.

Compliance with ethical standards

Funding

The study was performed on institutional budget funding.

Conflict of interest

The authors have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

For this type of study, formal consent is not required.

Supplementary material

10096_2017_3017_MOESM1_ESM.docx (109 kb)
ESM 1 (DOCX 109 kb)

References

  1. 1.
    Davies KA, Longshaw CM, Davis GL et al (2014) Underdiagnosis of Clostridium difficile across Europe: the European, multicentre, prospective, biannual, point-prevalence study of Clostridium Difficile infection in hospitalised patients with diarrhoea (EUCLID). Lancet Infect Dis 14:1208–1219. doi: 10.1016/S1473-3099(14)70991-0 CrossRefPubMedGoogle Scholar
  2. 2.
    Loo VG, Poirier L, Miller MA et al (2005) A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 353:2442–2449CrossRefPubMedGoogle Scholar
  3. 3.
    Lyytikäinen O, Turunen H, Sund R et al (2009) Hospitalizations and deaths associated with Clostridium difficile infection, Finland, 1996–2004. Emerg Infect Dis 15:761–765. doi: 10.3201/eid1505.081154 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Kanerva M, Mentula S, Virolainen-Julkunen A, Kärki T, Möttönen T, Lyytikäinen O; Hospital Infection Surveillance Team (2013) Reduction in Clostridium difficile infections in Finland, 2008–2010. J Hosp Infect 83:127–131. doi: 10.1016/j.jhin.2012.09.021 CrossRefPubMedGoogle Scholar
  5. 5.
    Könönen E, Rasinperä M, Virolainen A, Mentula S, Lyytikäinen O (2009) Diagnostic trends in Clostridium difficile detection in Finnish microbiology laboratories. Anaerobe 15:261–265. doi: 10.1016/j.anaerobe.2009.06.008 CrossRefPubMedGoogle Scholar
  6. 6.
    Kotila SM, Virolainen A, Snellman M, Ibrahem S, Jalava J, Lyytikäinen O (2011) Incidence, case fatality and genotypes causing Clostridium difficile infections, Finland, 2008. Clin Microbiol Infect 17:888–893. doi: 10.1111/j.1469-0691.2010.03384 CrossRefPubMedGoogle Scholar
  7. 7.
    Persson S, Jensen JN, Olsen KE (2011) Multiplex PCR method for detection of Clostridium difficile tcdA, tcdB, cdtA, and cdtB and internal in-frame deletion of tcdC. J Clin Microbiol 49:4299–4300. doi: 10.1128/JCM.05161-11 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Mentula S, Laakso S, Lyytikäinen O, Kirveskari J (2015) Differentiating virulent 027 and non-027 Clostridium difficile strains by molecular methods. Expert Rev Mol Diagn 15:1225–1229. doi: 10.1586/14737159.2015.1069710 CrossRefPubMedGoogle Scholar
  9. 9.
    Bouza E, Peláez T, Alonso R, Catalán P, Muñoz P, Créixems MR (2001) “Second-look” cytotoxicity: an evaluation of culture plus cytotoxin assay of Clostridium difficile isolates in the laboratory diagnosis of CDAD. J Hosp Infect 48:233–237CrossRefPubMedGoogle Scholar
  10. 10.
    Reller ME, Lema CA, Perl TM et al (2007) Yield of stool culture with isolate toxin testing versus a two-step algorithm including stool toxin testing for detection of toxigenic Clostridium difficile. J Clin Microbiol 45:3601–3605CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Tissari P (2008) Clostridium difficile-diagnostiikka tänään. Suomen Sairaalahygienialehti 26:304–306Google Scholar
  12. 12.
    Lindholm L, Kalluinen M, Eerola E, Meurman O, Virolainen A, Jalava J (2011) Correlation between Clostridium difficile toxin genes and the direct toxin detection assay results. In: Proceedings of the 21st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Milan, Italy, May 2011, P1986Google Scholar
  13. 13.
    Surawicz CM, Brandt LJ, Binion DG et al (2013) Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am J Gastroenterol 108:478–498; quiz 499. doi: 10.1038/ajg.2013.4 CrossRefPubMedGoogle Scholar
  14. 14.
    Crobach MJT, Planche T, Eckert C et al (2016) European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Clin Microbiol Infect 22(Suppl 4):S63–S81. doi: 10.1016/j.cmi.2016.03.010 CrossRefPubMedGoogle Scholar
  15. 15.
    Carroll KC, Bartlett JG (2011) Biology of Clostridium difficile: implications for epidemiology and diagnosis. Annu Rev Microbiol 65:501–521. doi: 10.1146/annurev-micro-090110-102824 CrossRefPubMedGoogle Scholar
  16. 16.
    Brecher SM, Novak-Weekley SM, Nagy E (2013) Laboratory diagnosis of Clostridium difficile infections: there is light at the end of the colon. Clin Infect Dis 57:1175–1181CrossRefPubMedGoogle Scholar
  17. 17.
    Hirvonen JJ, Kaukoranta SS (2014) Comparison of FecalSwab and ESwab devices for storage and transportation of diarrheagenic bacteria. J Clin Microbiol 52:2334–2339. doi: 10.1128/JCM.00539-14 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Kanerva M, Ollgren J, Voipio T, Mentula S, Lyytikäinen O (2015) Regional differences in Clostridium difficile infections in relation to fluoroquinolone and proton pump inhibitor use, Finland, 2008–2011. Infect Dis (Lond) 47(8):530–535. doi: 10.3109/23744235.2015.1026933 CrossRefGoogle Scholar
  19. 19.
    Planche T, Aghaizu A, Holliman R et al (2008) Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis 8:777–784. doi: 10.1016/S1473-3099(08)70233-0 CrossRefPubMedGoogle Scholar
  20. 20.
    Goldenberg SD, French GL (2011) Diagnostic testing for Clostridium difficile: a comprehensive survey of laboratories in England. J Hosp Infect 79:4–7. doi: 10.1016/j.jhin.2011.03.030 CrossRefPubMedGoogle Scholar
  21. 21.
    Alcalá L, Marín M, Martín A et al; Spanish Clostridium difficile Study Group (2011) Laboratory diagnosis of Clostridium difficile infection in Spain: a population-based survey. J Hosp Infect 79:13–17. doi: 10.1016/j.jhin.2011.05.017 CrossRefPubMedGoogle Scholar
  22. 22.
    Adler A, Schwartzberg Y, Samra Z, Schwartz O, Carmeli Y, Schwaber MJ; Israeli Clostridium difficile Diagnostics Study Group (2014) Trends and changes in Clostridium difficile diagnostic policies and their impact on the proportion of positive samples: a national survey. Clin Microbiol Infect 20(11):O904–O910. doi: 10.1111/1469-0691.12634 CrossRefPubMedGoogle Scholar
  23. 23.
    Spigaglia P, Barbanti F, Morandi M, Moro ML, Mastrantonio P (2016) Diagnostic testing for Clostridium difficile in Italian microbiological laboratories. Anaerobe 37:29–33. doi: 10.1016/j.anaerobe.2015.11.002 CrossRefPubMedGoogle Scholar
  24. 24.
    Bauer MP, Notermans DW, van Benthem BH et al (2011) Clostridium difficile infection in Europe: a hospital-based survey. Lancet 377:63–73CrossRefPubMedGoogle Scholar
  25. 25.
    Fitzpatrick F, Oza A, Gilleece A, O’Byrne AM, Drudy D; C. difficile subcommittee of the Health Protection Surveillance Centre (2008) Laboratory diagnosis of Clostridium difficile-associated disease in the Republic of Ireland: a survey of Irish microbiology laboratories. J Hosp Infect 68:315–321. doi: 10.1016/j.jhin.2008.01.025 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Bacterial Infections Unit, Department of Health SecurityNational Institute for Health and Welfare (THL)HelsinkiFinland
  2. 2.Infectious Disease Control Unit, Department of Health SecurityNational Institute for Health and Welfare (THL)HelsinkiFinland

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