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

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

Author information

Division of Digestive and Liver Diseases.
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Columbia University Medical Center, New York, New York.
UMass Memorial Children's Medical Center, Worcester, Massachusetts.
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
Center for Clinical Epidemiology and Biostatistics and the Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.



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.


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.


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.


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.


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

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