title: Clinical and Healthcare Burden of Multiple Recurrences of Clostridium difficile Infection.
abstract: 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.
authors.affiliation: Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Quebec, Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sheitoyan-Pesant
authors.affiliation: Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Quebec, Canada.
authors.forename: Claire Nour
authors.initials: CN
authors.lastname: Abou Chakra
authors.affiliation: Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Quebec, Canada.
authors.forename: Jacques
authors.initials: J
authors.lastname: Pépin
authors.affiliation: Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Quebec, Canada.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Marcil-Héguy
authors.affiliation: Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Quebec, Canada.
authors.forename: Vincent
authors.initials: V
authors.lastname: Nault
authors.affiliation: Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Quebec, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Valiquette
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002170:Canada / Q000453:epidemiology; D016360:Clostridioides difficile; D015331:Cohort Studies; D017281:Cost of Illness; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000191:economics / Q000453:epidemiology*; D006760:Hospitalization; D015994:Incidence; D008795:Metronidazole / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D014640:Vancomycin / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D008795:Metronidazole; D014640:Vancomycin
keywords: Clostridium difficile; complications; recurrence