Clinical and Healthcare Burden of Multiple Recurrences of Clostridium difficile Infection

Clin Infect Dis. 2016 Mar 1;62(5):574-580. doi: 10.1093/cid/civ958. Epub 2015 Nov 17.


Background: Clostridium difficile infection (CDI) is associated with a high risk of recurrence (rCDI). Few studies have focused on multiple recurrences. To evaluate the potential of novel treatments targeting recurrence, we assessed the burden and severity of rCDI.

Methods: This was a retrospective cohort of adults diagnosed with CDI in a hospital in Sherbrooke, Canada (1998-2013). An rCDI episode was defined by the reappearance of diarrhea leading to a treatment, with or without a positive toxin assay, within 14-60 days after the previous episode.

Results: We included 1527 patients. The probability of developing a first rCDI was 25% (354/1418); a second, 38% (128/334); a third, 29% (35/121); and a fourth or more, 27% (9/33). Two or more rCDIs were observed in 9% (128/1389) of patients. The risk of a first recurrence fluctuated over time, but there was no such variation for second or further recurrences. The proportion of severe cases decreased (47% for initial episodes, 31% for first recurrences, 25% for second, 17% for third), as did the risk of complicated CDI (5.8% to 2.8%). The severity and risk of complications of first recurrences decreased over time, while oral vancomycin was used more systemically. A hospital admission was needed for 34% (148/434) of recurrences.

Conclusions: This study documented the clinical and healthcare burden of rCDI: 34% of patients with rCDI needed admission, 28% developed severe CDI, and 4% developed a complication. Secular changes in the severity of recurrences could reflect variations in the predominant strain, or better management.

Keywords: Clostridium difficile; complications; recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Canada / epidemiology
  • Clostridioides difficile*
  • Cohort Studies
  • Cost of Illness*
  • Enterocolitis, Pseudomembranous / drug therapy
  • Enterocolitis, Pseudomembranous / economics
  • Enterocolitis, Pseudomembranous / epidemiology*
  • Hospitalization
  • Incidence
  • Metronidazole / therapeutic use
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Vancomycin / therapeutic use


  • Anti-Bacterial Agents
  • Metronidazole
  • Vancomycin