Use of Acid Suppression Medication is Associated With Risk for C. difficile Infection in Infants and Children: A Population-based Study

Clin Infect Dis. 2015 Sep 15;61(6):912-7. doi: 10.1093/cid/civ432. Epub 2015 Jun 9.


Background: Acid suppression medication is associated with Clostridium difficile infection (CDI) in adults and is increasingly prescribed to children. This study evaluated the relationship between acid suppression medication and incident CDI in children.

Methods: This was a population-based, nested case-control study. Patients were eligible if they were aged 0-17 years with 3 or more visits or 1 year or more of follow-up in the dataset. Patients were excluded if they had comorbidities that associate with CDI and might also associate with acid suppression medication. Patients with codes for CDI were matched 1:5 with control patients by age, sex, medical practice, time of entry into the dataset, and follow-up time. The primary exposure was use of acid suppression medication with proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) within 8-90 days.

Results: We identified 650 CDI cases and 3200 controls. The adjusted odds ratio (OR) for CDI and acid suppression medication was 7.66 (95% confidence interval [CI], 3.24-18.1). Acid suppression medication was associated with CDI in infants aged <1 year (OR, 5.24; 95% CI, 1.13-24.4) and children aged 1-17 years (OR, 9.33; 95% CI, 3.25-26.8). There was increased risk for CDI with PPIs compared with H2RAs and with recent compared with distant exposure.

Conclusions: Acid suppression medication associated with CDI in infants and children in the outpatient setting, with an effect based on medication timing. Increased risk for CDI should be factored into the decision to use acid suppression medication in children.

Keywords: Clostridium difficile infection; histamine-2 receptor antagonists; microbiome; pharmacoepidemiology; proton pump inhibitors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Clostridioides difficile / isolation & purification*
  • Clostridium Infections / chemically induced*
  • Clostridium Infections / epidemiology*
  • Colitis / chemically induced*
  • Colitis / epidemiology*
  • Female
  • Histamine H2 Antagonists / administration & dosage
  • Histamine H2 Antagonists / adverse effects*
  • Humans
  • Infant
  • Male
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Risk Assessment


  • Histamine H2 Antagonists
  • Proton Pump Inhibitors