Acid Suppressing Agents and Risk for Clostridium Difficile Infection in Pediatric Patients

INTRODUCTION: Acid suppressing agents, such as histamine 2 receptor antagonists (H2RA) and proton pump inhibitors (PPI) have been associated with increased Clostridium difficile infection (CDI) in adults. The objective of this study was to evaluate the association of acid suppressing therapy and the development of Clostridium difficile infection in the pediatric population.

METHODS: This was a retrospective case-control study. Children aged 1 through 17 years with a positive C. difficile polymerase chain reaction (PCR) obtained between June 1, 2008 and June 1, 2012 were randomly matched 1:1 to a control selected from patients with negative PCR during the same period. Clostridium difficile infection was defined by positive PCR. Demographic data and use of H2RA or PPI prior to PCR were extracted from patient medical records. Presence of possible CDI risk factors including hospitalization within the past 3 months, duration of hospitalization prior to positive/negative PCR, co-morbid conditions, prior antibiotic use, oral steroids, immunosuppressants, prokinetic agents, and chemotherapeutic agents was also recorded.

RESULTS: Four hundred and fifty-eight (229 PCR positive and 229 PCR negative) children were included. Children with CDI were younger than children without CDI (median [IQR] years 6 [2-11] vs. 8 [3 – 11], p=0.012). No difference was observed in acid suppressive therapy prior to PCR in CDI positive vs. negative patients (57.2% vs. 52.8%, p = 0.348). Of patients with acid suppressing therapy prior to obtaining a PCR, more CDI positive patients received acid suppressive therapy at home. (76.3% vs. 60.3%, p=0.006). In this subset, no difference was observed in PPI utilization (45% vs. 46.3%, p=0.843) between CDI positive and negative patients, but H2RA utilization was greater in the CDI positive patients (32.8% vs. 14.9%, p = 0.001). Risk factors for CDI were not different between the two groups. Logistic regression analysis demonstrated that H2RA therapy at home (OR: 2.9; 95% CI: 1.47–5.71) was an independent CDI predictor.

CONCLUSION: In this pediatric population, children receiving home acid suppressive therapy with H2RAs have nearly 3 times greater risk for CDI than children not receiving H2RA therapy. These results suggest the need for continued monitoring and study of H2RA use in the pediatric population.