Association of Clostridium difficile infections with acid suppression medications in children

J Pediatr. 2014 Nov;165(5):979-84.e1. doi: 10.1016/j.jpeds.2014.06.062. Epub 2014 Aug 8.


Objective: Multiple studies have confirmed associations between acid suppression medication and Clostridium difficile infections (CDIs) in adults. Therefore, we sought to evaluate an association between acid suppression medications and CDI in children.

Study design: A retrospective self-controlled case series was performed utilizing billing records from the TRICARE Management Activity military health system database. Children ages 2-18 years from October 1, 2001 to July 31, 2013, who had an outpatient or inpatient record of CDI diagnosis were included. The relative incidences (RIs) of CDI or recurrent CDI were calculated comparing time periods prescribed and not prescribed proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs).

Results: There were 2531 cases of CDI among 2437 patients, and 1190 (48.8%) were prescribed acid suppression medications. CDI were more likely to occur during periods when patients were prescribed a PPI (RI 2.36; 95% CI 2.22-2.52), H2RA (RI 1.95; 95% CI 1.63-2.34), or during periods while prescribed both simultaneously (RI 2.40; 95% CI 1.90-3.04). There were 265 (10.4%) cases that were classified as recurrent among 217 (8.9%) patients. Recurrent CDI also was found to be more likely during prescription periods of PPI (RI 1.74; 95% CI 1.51-2.00) and H2RA (RI 2.63; 95% CI 1.89-3.66).

Conclusions: Acid suppression medications are associated with an increased risk of CDI and recurrent CDI. Judicious use of acid suppression medication should be considered, especially among those at highest risk for CDI.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Antacids / adverse effects*
  • Child
  • Child, Preschool
  • Clostridioides difficile*
  • Clostridium Infections / chemically induced*
  • Clostridium Infections / epidemiology
  • Clostridium Infections / microbiology
  • Female
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / epidemiology
  • Gastrointestinal Diseases / microbiology
  • Histamine H2 Antagonists / adverse effects*
  • Humans
  • Incidence
  • Male
  • Proton Pump Inhibitors / adverse effects*
  • Retrospective Studies
  • Risk Factors


  • Antacids
  • Histamine H2 Antagonists
  • Proton Pump Inhibitors