Assessing the Risk of Hospital-Acquired Clostridium Difficile Infection With Proton Pump Inhibitor Use: A Meta-Analysis

Abstract

BACKGROUND Clostridium difficile is the principal infectious cause of antibiotic-associated diarrhea and accounts for 12% of hospital-acquired infections. Recent literature has shown an increased risk of C. difficile infection (CDI) with proton pump inhibitor (PPI) use. OBJECTIVE To conduct a systematic assessment of the risk of hospital-acquired CDI following exposure to PPI. METHODS We searched multiple databases for studies examining the relationship between PPI and hospital-acquired CDI. Pooled odds ratios were generated and assessment for heterogeneity performed. RESULTS We found 23 observational studies involving 186,033 cases that met eligibility criteria. Across studies, 10,307 cases of hospital-acquired CDI were reported. Significant heterogeneity was present; therefore, a random effects model was used. The pooled odds ratio was 1.81 (95% CI, 1.52-2.14), favoring higher risk of CDI with PPI use. Significant heterogeneity was present, likely due to differences in assessment of exposure, study population, and definition of CDI. DISCUSSION This meta-analysis suggests PPIs significantly increase the risk of hospital-acquired CDI. Given the significant health and economic burden of CDI and the risks of PPI, optimization of PPI use should be included in a multifaceted approach to CDI prevention. Infect Control Hosp Epidemiol 2016;1408-1417.

Figure 1

PRISMA flow diagram of study selection criteria

Figure 2

Funnel plot to assess the potential impact of publication bias. Effect Size

Figure 3

Forest plot of the association between proton pump inhibitor and C. difficile infection. The vertical line corresponds to the no difference point between two groups. Horizontal lines represent the 95% CIs.

Figure 4

Forest plot of the association between proton pump inhibitor and C. difficile infection in those studies defining CDI cases in the presence of symptoms.

Figure 5

Forest plot of the association between proton pump inhibitor and C. difficile infection in those studies not requiring symptoms for CDI case definition.