Proton pump inhibitors as a risk factor for paediatric Clostridium difficile infection

Aliment Pharmacol Ther. 2010 Apr;31(7):754-9. doi: 10.1111/j.1365-2036.2009.04229.x. Epub 2009 Dec 29.


Background: Proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RAs) may play an important role on the onset of Clostridium difficile-associated disease (CDAD) in adults. The impact of Clostridium difficile on children treated with gastric acid-suppressing agents remains unknown.

Aim: To investigate the relationship between CDAD and exposure to acid suppressive therapy in hospitalized paediatric patients.

Methods: We reviewed the medical records of children, with a diagnosis of protracted diarrhoea and abdominal pain, whose stool was analysed for C. difficile toxins. We identified 68 patients with CDAD. For each patient, we randomly selected one control subjects with stool analysis negative for C. difficile. Comorbid illnesses, previous hospitalizations, antibiotics, corticosteroids, immunosuppressants and gastric acid suppressing exposures were recorded.

Results: The use of PPI was significantly higher in C. difficile positive group compared with C. difficile negative group [odds ratio (OR): = 4.5; 95% confidence interval (CI) = 1.4-14.4]. We also found a trend for the use of H(2)RAs in patients infected by C. difficile compared with C. difficile negative comparison group (OR: = 3.8; 95% CI = 0.7-18.9).

Conclusions: Children exposed to PPIs therapy seem to be at higher risk for the development of Clostridium difficile-associated disease.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Clostridioides difficile / drug effects*
  • Diarrhea / chemically induced*
  • Diarrhea / microbiology
  • Enterocolitis, Pseudomembranous / chemically induced*
  • Enterocolitis, Pseudomembranous / microbiology
  • Epidemiologic Methods
  • Female
  • Histamine H2 Antagonists / adverse effects
  • Humans
  • Infant
  • Male
  • Proton Pump Inhibitors / adverse effects*


  • Histamine H2 Antagonists
  • Proton Pump Inhibitors