Role of Proton Pump Inhibitors in Recurrence of Clostridium difficile Infection: Systematic Review and Meta-Analysis

Abstract

Introduction: The rising incidence of clostridium difficile infection (CDI) has resulted in increasing healthcare burden with CDI reoccurrence up to 20% after the initial episode. Although proton pump inhibitors (PPI) use is a well-established risk factor for first episode of CDI, its role in recurrent CDI is still controversial. Our aim is to examine the role of PPI in recurrence of CDI, as well as to determine other potential risk factors. Methods: We searched MEDLINE, Embase and Web of Science databases up to March 2016 for observational and controlled trials assessing CDI recurrence rated. Review of titles/abstracts, full review and data abstraction were performed by two authors. Study quality was assessing using PRISMA guidelines. The primary analysis assessed recurrence rate of CDI in 60-90 days post-treatment of initial episode of CDI in presence of continued PPI use. Pooled subgroup analyses were done to evaluate other plausible risk factors. Statistical analyses were performed using RStudio with Hartung-Knapp correction for random effects modeling. Dichotomous outcomes were addressed with pooled risk ratios (RR) and 95% confidence intervals (CI). Results: A total of 1157 citations were identified. Of these 18 articles met inclusion criteria and were analyzed. A total of 13525 patients were in the pooled cohort with 4847(36 %) taking PPI. Recurrent CDI occurred in 2305 patients with 48 % of events (1098 patients) occurring in the PPI group. There was a significant association of PPI use with recurrent CDI (RR 1.70, 95% CI:1.27-2.28, I2: 76%, Chi2: 72). On pooled subgroup analyses, there was no statistical significant association of recurrent CDI with gender, renal disease, diabetes mellitus or steroid use.Figure 1Conclusion: Our study shows that an unusually large number of patients continue to take PPIs after initial CDI treatment. There is a strong association between continued PPI use and risk of CDI recurrence in the subsequent 90 days. The possible mechanism is the increased gut pH with PPI use facilitates growth of gastrointestinal flora and impairment of leukocytes by PPI. The data presented herein emphasizes the importance of re-assessment of the need for PPI therapy in all patients.