An association between proton pump inhibitor (PPI) therapy and bacterial gastroenteritis has been suggested as well as contradicted. We hypothesize that previous case-control studies have suffered from selection or information bias. Therefore, we designed a nested case control study within The Rotterdam Cohort, a prospective cohort study, to examine the association between the use of PPIs and occurrence of bacterial gastroenteritis.
The Rotterdam Study is a population-based cohort study among 14 926 subjects aged 45 years and older with up to 24 years of follow-up. Analyses were performed with a generalized estimating equations method in participants who handed-in a diagnostic stool sample. The model was adjusted for age and sex and additionally for covariables changing the point estimate (β) of current PPI use by more than 10% or if considered clinically relevant. Furthermore, a nested case-control analysis was performed using the total cohort as a reference group.
A bacterial microorganism was isolated in 125 samples, whereas 1174 samples were culture negative. We included age, sex, cohort, calendar date, past use of proton pump inhibitors, past use of H2-receptor antagonists, and current use of chronic medication in the final model. In the generalized estimating equations analysis, we found that participants with a bacterial gastroenteritis were more likely than controls to be current users of PPIs (adjusted OR, 1.94; 95% CI 1.15-3.25). Different sensitivity analyses did not change this result. A considerably higher effect was observed (adjusted OR 6.14; 95% CI 3.81-9.91), using the total cohort as a reference in a nested case-control analysis.
Current PPI therapy is associated with an increased risk of bacterial gastroenteritis. However, by reducing the risk of selection and information bias in our study design, we demonstrated that the effect is lower than previously assumed.
R. J. Hassing,
A. Hofman, None
B. H. C. Stricker, None