Risk of Clostridium difficile Infection with the Use of a Proton Pump Inhibitor for Stress Ulcer Prophylaxis in Critically Ill Patients

Gut Liver. 2016 Jul 15;10(4):581-6. doi: 10.5009/gnl15324.


Background/aims: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly prescribed for stress ulcer prophylaxis (SUP) in critically ill patients. Several studies have suggested that the use of PPIs is a potential risk factor for Clostridium difficile infection (CDI). We compared the incidences of CDI in the PPI group and H2RA group for SUP in critically ill patients.

Methods: From August 2005 to July 2012, the incidences of CDI were retrospectively analyzed in patients who were admitted directly to intensive care units and stayed for more than 3 days. SUP-related CDI was defined as a CDI diagnosed during the SUP period. Patient clinical data were analyzed to identify potential risk factors for SUP-related CDI.

Results: Of the 1,005 patients enrolled (444 patients received PPI and 561 received H2RA), 38 (3.8%) were diagnosed with SUP-related CDI. The incidence of SUP-related CDI was considerably higher in patients who received PPI than in those who received H2RA (6.7% vs 1.8%). PPI use for SUP (odds ratio [OR], 3.3; confidence interval [CI], 1.5 to 7.1; p=0.003) and diabetes mellitus (OR, 2.3; CI, 1.2 to 4.7; p=0.019) were independent risk factors for SUP-related CDI.

Conclusions: PPI therapy is associated with a higher risk of SUP-related CDI than H2RA therapy in critically ill patients.

Keywords: Clostridium difficile; Critical care; Histamine-2 receptor antagonist; Proton pump inhibitor.

MeSH terms

  • Aged
  • Clostridioides difficile / drug effects
  • Clostridium Infections / chemically induced*
  • Clostridium Infections / epidemiology
  • Critical Illness / therapy*
  • Cross Infection / chemically induced*
  • Cross Infection / epidemiology
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Odds Ratio
  • Pressure Ulcer / prevention & control*
  • Proton Pump Inhibitors / adverse effects*
  • Retrospective Studies
  • Risk Factors


  • Proton Pump Inhibitors