Continuous Proton Pump Inhibitor Therapy and the Associated Risk of Recurrent Clostridium difficile Infection

JAMA Intern Med. 2015 May;175(5):784-91. doi: 10.1001/jamainternmed.2015.42.


Importance: Clostridium difficile infection (CDI) is associated with significant morbidity, mortality, and a high risk of recurrence. Proton pump inhibitor (PPI) use is associated with an initial episode of CDI, and PPIs are frequently overprescribed. For many, the use of PPIs could likely be discontinued before CDI recurrence.

Objectives: To determine whether PPI use was associated with a risk of initial CDI recurrence, to assess what proportion of patients who developed CDI were taking a PPI for a non-evidence-based indication, and to evaluate whether physicians discontinued unnecessary PPIs in the context of CDI.

Design, setting, and participants: We conducted a retrospective cohort study of incident health care-associated CDI cases to determine the association between continuous PPI use and CDI recurrence within 90 days. The setting was 2 university-affiliated hospitals, the 417-bed Montreal General Hospital (Montreal, Quebec, Canada) and the 517-bed Royal Victoria Hospital (Montreal, Quebec, Canada). The cohort consisted of 754 patients who developed health care-associated CDI between January 1, 2010, and January 30, 2013, and who survived for a minimum of 15 days after their initial episode of nosocomial CDI.

Exposure: Continuous PPI use.

Main outcomes and measures: Recurrence of CDI within 15 to 90 days of the initial episode.

Results: Using a multivariable Cox proportional hazards model, the cause-specific hazard ratios for recurrence were 1.5 (95% CI, 1.1-2.0) for age older than 75 years, 1.5 (95% CI, 1.1-2.0) for continuous PPI use, 1.003 (95% CI, 1.002-1.004) per day for length of stay, and 1.3 (95% CI, 0.9-1.7) for antibiotic reexposure. The use of PPIs was common (60.7%), with only 47.1% of patients having an evidence-based indication. Proton pump inhibitors were discontinued in only 3 patients with CDI.

Conclusions and relevance: After adjustment for other independent predictors of recurrence, patients with continuous PPI use remained at elevated risk of CDI recurrence. We suggest that the cessation of unnecessary PPI use should be considered at the time of CDI diagnosis.

MeSH terms

  • Age Factors
  • Aged
  • Anti-Bacterial Agents* / classification
  • Anti-Bacterial Agents* / therapeutic use
  • Canada / epidemiology
  • Clostridioides difficile / drug effects*
  • Clostridium Infections* / diagnosis
  • Clostridium Infections* / epidemiology
  • Clostridium Infections* / etiology
  • Clostridium Infections* / physiopathology
  • Clostridium Infections* / therapy
  • Cross Infection* / diagnosis
  • Cross Infection* / epidemiology
  • Cross Infection* / etiology
  • Cross Infection* / physiopathology
  • Cross Infection* / therapy
  • Female
  • Humans
  • Inappropriate Prescribing* / adverse effects
  • Inappropriate Prescribing* / prevention & control
  • Inappropriate Prescribing* / statistics & numerical data
  • Incidence
  • Length of Stay / statistics & numerical data
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / therapeutic use*
  • Retrospective Studies
  • Risk Factors
  • Secondary Prevention* / methods
  • Secondary Prevention* / statistics & numerical data
  • Withholding Treatment


  • Anti-Bacterial Agents
  • Proton Pump Inhibitors