Administration of Proton Pump Inhibitors in Critically Ill Medical Patients Is Associated With Increased Risk of Developing Clostridium Difficile-Associated Diarrhea

J Crit Care. 2014 Aug;29(4):696.e11-5. doi: 10.1016/j.jcrc.2014.03.002. Epub 2014 Mar 7.


Purpose: Proton pump inhibitors (PPIs) effectively prevent gastrointestinal bleedings in critically ill patients at the intensive care unit (ICU). In non-ICU hospitalized patients, PPI administration increases the risk of infectious complications, especially Clostridium difficile-associated diarrhea (CDAD); but no such data are available for the ICU setting.

Materials and methods: This is a retrospective, observational, single-center analysis (1999-2010) including 3286 critically ill patients.

Results: A total of 91.3% of patients received stress ulcer prophylaxis by PPI (55.6%), histamine 2 receptor antagonists (5.8%), sucralfate (10.1%), or combinations (19.8%). Only 29 (0.9%) of 3286 patients developed gastrointestinal bleedings during the course of ICU treatment, independent from the type of prophylaxis. The PPIs were not an independent risk factor for nosocomial pneumonia. One hundred and ten (3.3%) patients developed CDAD during the course of ICU treatment, which was associated with prolonged ICU stay and increased ICU mortality (odds ratio, 1.59). Similar to fluoroquinolones and cephalosporins, PPI was identified as an independent risk factor (odds ratio, 3.11) for developing CDAD at the ICU by multivariate analysis.

Conclusions: Proton pump inhibitor therapy was an independent risk factor for CDAD in medical ICU patients. Instead of routine PPI use for bleeding prophylaxis, further trials should investigate risk-adjusted algorithms, balancing benefits, and threats of PPI medication.

Keywords: CDAD; Gastrointestinal bleeding; Nosocomial pneumonia; PPI; Sepsis; Stress ulcer.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use
  • Clostridium difficile*
  • Critical Illness
  • Diarrhea / chemically induced*
  • Diarrhea / microbiology
  • Female
  • Gastrointestinal Hemorrhage / prevention & control
  • Histamine H2 Antagonists / therapeutic use
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • Odds Ratio
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Retrospective Studies
  • Risk Factors
  • Stomach Ulcer / prevention & control
  • Sucralfate / therapeutic use
  • Young Adult


  • Anti-Bacterial Agents
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors
  • Sucralfate