Magnitude and direction of the association between Clostridium difficile infection and proton pump inhibitors in adults and pediatric patients: a systematic review and meta-analysis.

BACKGROUND: Clostridium difficile infection (CDI) is a cause of increased morbidity and health care costs among hospitalized patients. Proton pump inhibitors (PPIs) are mainly used for the treatment of acid-related upper gastrointestinal diseases. The aim of the study was to assess the risks associated with initial and recurrent CDI in adult and pediatric patients treated with PPIs.

METHODS: A systematic search was performed using PubMed (Medline), Embase, and Web of Science with the following search terms: ("proton pump inhibitor," "PPI," or "acid suppression") AND ("infection," "diarrhea," "diarrhoea," "colitis," or "disease") AND ("Clostridium difficile"). Meta-analysis was performed using Revman5.3 software. Pooled odds ratios (ORs) presented as standard plots with 95% confidence intervals (CIs) were determined.

RESULTS: Sixty-seven eligible studies were selected. PPI use was significantly associated with risk of CDI (OR 2.34, 95% CI 1.94-2.82; P < 0.00001). Pooled data from twelve studies demonstrated a significant association between PPI use and recurrent CDI (OR 1.73, 95% CI 1.39-2.15; P = 0.02). Subgroup analysis revealed significant associations between PPI use and an increased incidence of CDI among adult (OR 2.30, 95% CI 1.89-2.80; P < 0.00001) and pediatric (OR 3.00, 95% CI 1.44-6.23; P < 0.00001) patients.

CONCLUSIONS: PPI use was associated with CDI in adult and pediatric patients, and with recurrent CDI. Although many risk factors are associated with the occurrence and recurrence of CDI, consideration should be given to not administering PPIs at any age if they are unnecessary.