Gastric Acid Suppression and Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis

Abstract

Purpose:Clostridium difficile infection (CDI) is the most common cause of nosocomial diarrhea with the risk of recurrence ranging from 20-65%. Gastric acid suppression is associated with an increased risk of CDI, however, studies regarding the risk of recurrent CDI in patients on acid suppression have shown conflicting results. Up to 50% or more of patients with CDI are on concomitant gastric acid suppression medications. We performed a systematic review and meta-analysis to study the association between gastric acid suppression medications and the risk of recurrent CDI. Methods: A systematic search of Medline, Embase, and Web of Science was performed up to April 2012 and a manual review of the literature was performed. Studies were included if they assessed the association between exposure to gastric acid suppression medications (histamine 2 receptor blocker or proton pump inhibitor) and recurrent CDI as an outcome; and reported relative risks or odds ratio (OR) or provided data for their calculation. Summary OR estimates with 95% confidence intervals (CIs) were calculated using the random-effects model using Review Manager version 5.1 (Cochran Inc). Results: Eleven studies (10 observational and 1 post-hoc analysis of a randomized controlled trial) reporting 899 cases of recurrent CDI in 3,929 patients with CDI were included. Of the 3,929 patients with CDI, 1,983 (50.4%) were on acid suppression. The rate of recurrent CDI in patients on acid suppression was 24.1% (n=477/1,983), compared to 21.7% (n=422/1,946) in patients without acid suppression. Meta-analysis of studies using the random effects model did not show an increased risk of recurrent CDI in patients on gastric acid suppression medications (OR 1.40, 95% Cl 0.92 - 2.13, p=0.24). There was significant heterogeneity among the studies with I2 of 77% and Cochran's Q p<0.0001. Sensitivity analyses based on the definition of recurrent CDI revealed that acid suppression medication use was associated with increased risk of recurrence in studies defining recurrent CDI within 90 days (OR 1.75, 95% Cl 1.06 - 2.87, p=0.03) but not in studies defining recurrent CDI up to 60 days (OR 1.32, 95% Cl 0.58 - 2.98, p=0.67). Conclusion: Meta-analyses of existing studies does not indicate that concomitant use of gastric acid suppression medications is associated with an increased risk of recurrent CDI within 60 days, but may be associated with reinfection through 90 days.