Skip to main content
SpringerLink
Log in

Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case–control study

  • Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

Increased incidence and severity of Clostridium difficile infections (CDIs) is of major concern. However, by minimizing known risk factors, the incidence can be decreased. The aim of this investigation was to calculate the incidence and assess risk factors for CDI in our population. A 1-year prospective population-based nationwide study in Iceland of CDIs was carried out. For risk factor evaluation, each case was matched with two age- and sex-matched controls that tested negative for C. difficile toxin. A total of 128 CDIs were identified. The crude incidence was 54 cases annually per 100,000 population >18 years of age. Incidence increased exponentially with older age (319 per 100,000 population >86 years of age). Community-acquired origin was 27 %. Independent risk factors included: dicloxacillin (odds ratio [OR]: 7.55, 95 % confidence interval [CI]: 1.89–30.1), clindamycin (OR: 6.09, 95 % CI: 2.23–16.61), ceftriaxone (OR: 4.28, 95 % CI: 1.59–11.49), living in a retirement home (OR: 3.9, 95 % CI: 1.69–9.16), recent hospital stay (OR: 2.3, 95 % CI: 1.37–3.87). Proton pump inhibitors (PPIs) were used by 60/111 (54 %) versus 91/222 (41 %) (p = 0.026) and ciprofloxacin 19/111 (17 %) versus 19/222 (9 %) (p = 0.027) for cases and controls, respectively. In all, 75 % of primary CDIs treated with metronidazole recovered from one course of treatment. CDI was mostly found among elderly patients. The most commonly identified risk factors were broad-spectrum antibiotics and recent contact with health care institutions. PPI use was significantly more prevalent among CDI patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CDI:

Clostridium difficile infection

PPI:

Proton pump inhibitor

CD:

Clostridium difficile

NUH:

National University Hospital of Iceland

ATC:

Anatomical Therapeutic Chemical Classification System

ELISA:

Enzyme-linked immunosorbent assay

CA-CDI:

Community-acquired Clostridium difficile infection

References

  1. Karlström O, Fryklund B, Tullus K, Burman LG (1998) A prospective nationwide study of Clostridium difficile-associated diarrhea in Sweden. The Swedish C. difficile Study Group. Clin Infect Dis 26(1):141–145

    Article  PubMed  Google Scholar 

  2. Pépin J, Valiquette L, Alary ME, Villemure P, Pelletier A, Forget K, Pépin K, Chouinard D (2004) Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ 171(5):466–472

    Article  PubMed  Google Scholar 

  3. Elixhauser A, Jhung M (2008) Statistical brief #50. Clostridium difficile-associated disease in U.S. Hospitals, 1993–2005. Available online at: http://www.hcup-us.ahrq.gov/reports/statbriefs/sb50.pdf

  4. Kuijper EJ, Coignard B, Tüll P; ESCMID Study Group for Clostridium difficile; EU Member States; European Centre for Disease Prevention and Control (2006) Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect 12(Suppl 6):2–18

    Article  PubMed  CAS  Google Scholar 

  5. Pépin J, Valiquette L, Gagnon S, Routhier S, Brazeau I (2007) Outcomes of Clostridium difficile-associated disease treated with metronidazole or vancomycin before and after the emergence of NAP1/027. Am J Gastroenterol 102(12):2781–2788

    Article  PubMed  Google Scholar 

  6. Jamal W, Rotimi VO, Brazier J, Duerden BI (2005) Analysis of prevalence, risk factors and molecular epidemiology of Clostridium difficile infection in Kuwait over a 3-year period. Anaerobe 16(6):560–565

    Article  Google Scholar 

  7. Hensgens MP, Goorhuis A, van Kinschot CM, Crobach MJ, Harmanus C, Kuijper EJ (2011) Clostridium difficile infection in an endemic setting in the Netherlands. Eur J Clin Microbiol Infect Dis 30(4):587–593

    Article  PubMed  CAS  Google Scholar 

  8. Raveh D, Rabinowitz B, Breuer GS, Rudensky B, Yinnon AM (2006) Risk factors for Clostridium difficile toxin-positive nosocomial diarrhoea. Int J Antimicrob Agents 28(3):231–237

    Article  PubMed  CAS  Google Scholar 

  9. Sundram F, Guyot A, Carboo I, Green S, Lilaonitkul M, Scourfield A (2009) Clostridium difficile ribotypes 027 and 106: clinical outcomes and risk factors. J Hosp Infect 72(2):111–118

    Article  PubMed  CAS  Google Scholar 

  10. Al-Tureihi FI, Hassoun A, Wolf-Klein G, Isenberg H (2005) Albumin, length of stay, and proton pump inhibitors: key factors in Clostridium difficile-associated disease in nursing home patients. J Am Med Dir Assoc 6(2):105–108

    Article  PubMed  Google Scholar 

  11. Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S, Leblanc M, Rivard G, Bettez M, Primeau V, Nguyen M, Jacob CE, Lanthier L (2005) Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 41(9):1254–1260

    Article  PubMed  Google Scholar 

  12. Howell MD, Novack V, Grgurich P, Soulliard D, Novack L, Pencina M, Talmor D (2010) Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med 170(9):784–790

    Article  PubMed  Google Scholar 

  13. Kuntz JL, Chrischilles EA, Pendergast JF, Herwaldt LA, Polgreen PM (2011) Incidence of and risk factors for community-associated Clostridium difficile infection: a nested case–control study. BMC Infect Dis 11:194

    Article  PubMed  Google Scholar 

  14. Fellmeth G, Yarlagadda S, Iyer S (2010) Epidemiology of community-onset Clostridium difficile infection in a community in the South of England. J Infect Public Health 3(3):118–123

    Article  PubMed  Google Scholar 

  15. Svenungsson B, Burman LG, Jalakas-Pörnull K, Lagergren A, Struwe J, Akerlund T (2003) Epidemiology and molecular characterization of Clostridium difficile strains from patients with diarrhea: low disease incidence and evidence of limited cross-infection in a Swedish teaching hospital. J Clin Microbiol 41(9):4031–4037

    Article  PubMed  CAS  Google Scholar 

  16. Statistics Iceland (2011) Population. Available online at: http://www.statice.is/Statistics/Population

  17. Ricciardi R, Rothenberger DA, Madoff RD, Baxter NN (2007) Increasing prevalence and severity of Clostridium difficile colitis in hospitalized patients in the United States. Arch Surg 142(7):624–631, discussion 631

    Article  PubMed  Google Scholar 

  18. Gravel D, Miller M, Simor A, Taylor G, Gardam M, McGeer A, Hutchinson J, Moore D, Kelly S, Boyd D, Mulvey M (2009) Health care-associated Clostridium difficile infection in adults admitted to acute care hospitals in Canada: a Canadian Nosocomial Infection Surveillance Program Study. Clin Infect Dis 48(5):568–576

    Article  PubMed  Google Scholar 

  19. Kvaran RB, Valsdóttir EB, Sigurdsson HK, Gottfredsson M (2010) Clostridium difficile infections at Landspítali—1998–2008. Laeknabladid 96(9):523–529

    PubMed  Google Scholar 

  20. Dubberke ER, Reske KA, Yan Y, Olsen MA, McDonald LC, Fraser VJ (2007) Clostridium difficile-associated disease in a setting of endemicity: identification of novel risk factors. Clin Infect Dis 45(12):1543–1549

    Article  PubMed  Google Scholar 

  21. Wilcox MH, Mooney L, Bendall R, Settle CD, Fawley WN (2008) A case–control study of community-associated Clostridium difficile infection. J Antimicrob Chemother 62(2):388–396

    Article  PubMed  CAS  Google Scholar 

  22. Bauer MP, Veenendaal D, Verhoef L, Bloembergen P, van Dissel JT, Kuijper EJ (2009) Clinical and microbiological characteristics of community-onset Clostridium difficile infection in The Netherlands. Clin Microbiol Infect 15(12):1087–1092

    Article  PubMed  CAS  Google Scholar 

  23. Bartlett JG (2002) Clinical practice. Antibiotic-associated diarrhea. N Engl J Med 346(5):334–339

    Article  PubMed  Google Scholar 

  24. Loo VG, Poirier L, Miller MA, Oughton M, Libman MD, Michaud S, Bourgault AM, Nguyen T, Frenette C, Kelly M, Vibien A, Brassard P, Fenn S, Dewar K, Hudson TJ, Horn R, René P, Monczak Y, Dascal A (2005) A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 353(23):2442–2449

    Article  PubMed  CAS  Google Scholar 

  25. Kuijper EJ, van den Berg RJ, Debast S, Visser CE, Veenendaal D, Troelstra A, van der Kooi T, van den Hof S, Notermans DW (2006) Clostridium difficile ribotype 027, toxinotype III, the Netherlands. Emerg Infect Dis 12(5):827–830

    Article  PubMed  Google Scholar 

  26. Kuijper EJ, Barbut F, Brazier JS, Kleinkauf N, Eckmanns T, Lambert ML, Drudy D, Fitzpatrick F, Wiuff C, Brown DJ, Coia JE, Pituch H, Reichert P, Even J, Mossong J, Widmer AF, Olsen KE, Allerberger F, Notermans DW, Delmée M, Coignard B, Wilcox M, Patel B, Frei R, Nagy E, Bouza E, Marin M, Akerlund T, Virolainen-Julkunen A, Lyytikäinen O, Kotila S, Ingebretsen A, Smyth B, Rooney P, Poxton IR, Monnet DL (2008) Update of Clostridium difficile infection due to PCR ribotype 027 in Europe, 2008. Euro Surveill 13(31). pii: 18942

    Google Scholar 

  27. Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, Monnet DL, van Dissel JT, Kuijper EJ; ECDIS Study Group (2011) Clostridium difficile infection in Europe: a hospital-based survey. Lancet 377(9759):63–73

    Article  PubMed  Google Scholar 

  28. Crobach MJ, Dekkers OM, Wilcox MH, Kuijper EJ (2009) European Society of Clinical Microbiology and Infectious Diseases (ESCMID): data review and recommendations for diagnosing Clostridium difficile-infection (CDI). Clin Microbiol Infect 15(12):1053–1066

    Article  PubMed  CAS  Google Scholar 

  29. Hensgens MP, Goorhuis A, Dekkers OM, Kuijper EJ (2011) Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother 67(3):742–748

    Article  PubMed  Google Scholar 

Download references

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Faculty of Medicine, University of Iceland, Reykjavík, Iceland

    I. Vesteinsdottir & E. S. Bjornsson

  2. Department of Gastroenterology and Hepatology, The National University Hospital of Iceland, Hringbraut, 101, Reykjavík, Iceland

    S. Gudlaugsdottir & E. S. Bjornsson

  3. Department of Pharmacy, University of Iceland, Reykjavík, Iceland

    R. Einarsdottir

  4. Department of Gastroenterology, Skåne University Hospital, Lund, Sweden

    E. Kalaitzakis

  5. Department of Clinical Chemistry, Akureyri District Hospital, Akureyri, Iceland

    O. Sigurdardottir

Authors
  1. I. Vesteinsdottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Gudlaugsdottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Einarsdottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Kalaitzakis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. O. Sigurdardottir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E. S. Bjornsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. S. Bjornsson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vesteinsdottir, I., Gudlaugsdottir, S., Einarsdottir, R. et al. Risk factors for Clostridium difficile toxin-positive diarrhea: a population-based prospective case–control study. Eur J Clin Microbiol Infect Dis 31, 2601–2610 (2012). https://doi.org/10.1007/s10096-012-1603-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-012-1603-0

Keywords

Search

Navigation