Most studies report such an association but its strength has varied among studies.
Many earlier reviews and meta-analyses had significant limitations, including use of unadjusted data from observational studies, and not assessing heterogeneity (variation in study outcomes) and the effect of publication bias1. A more recent meta-analysis of over 40 citations found an association between PPI use and CDI (O.R. 1.51, 95% CI, 1.26–1.83) adjusting for publication bias, but the association was weakened by the presence of significant heterogeneity in the published studies1. For the general population, the strength of the association was relatively weak (number needed to harm [NNTH] 3925 at 1 year), while for hospitalized patients it was much stronger (NNTH 50 at 2 weeks).
It is unclear how PPIs might increase risk of CDI as C. difficile spores are not killed by gastric acid2. They may interfere with the killing of the vegetative form of C. difficile by inhibiting gastric acid secretion or may delay gastric emptying with associated high intragastric bile salts which may trigger spore germination in the stomach; neither hypothesis has been proven, however2. Although a causal relationship has not been proven, judicious use of PPIs in high risk patients for CDI is advised.
- Tleyjeh IM, Bin Abdulhak AA, Riaz M, et al. (2012) Association between proton pump inhibitor therapy and Clostridium difficile infection: A contemporary systematic review and meta-analysis. PLoS ONE 2012; 7: e50836.
- Nerandzic MM, Pultz MJ, Donskey CJ. Examination of potential mechanisms to explain the association between proton pump Inhibitors and Clostridium difficile infection. Antimicrob Agents Chemother 2009;53(10): 4133–4137.