LAUSR

Clostridium difficile causes almost half a million infections annually among hospitalized and community-dwelling patients in the United States, and approximately 1 in 5 patients will develop arecurrentCdifficile infection.1 Therefore, identificationofmodifiable risk factors for incident and recurrent C difficile infection is a public health priority. In this issue of JAMA Internal Medicine, Tariq et al2 conducted a high-quality meta-analysis of 16 observational studies examining the association between gastric acid suppressants, such as proton-pump inhibitors (PPIs) or histamine H2-receptor blockers (H2Bs), and recurrent C difficile infection. They observed a 50% increase in odds of recurrent C difficile infection among patients receiving PPIs or H2Bs compared with patients not taking gastric acid suppressants. Because patients who take gastric acid suppressants are different from, and most likely sicker than, those who do not take gastric acid suppressants (eg, higher rates of diabetes, peptic ulcer disease, and antibiotic use; longer hospitalizations; and more intensive care unit days), it is reassuring that the observed association was relatively robust when restricted to cohort studies and studies that adjusted for confounders. However, an unbiased assessment without the risk of unmeasured confounding would require randomized clinical trials of gastric acid suppressant continuation vs withdrawal among patients with C difficile colitis who are also using chronic gastric acid suppressants. In the meantime, these findings support a strategy of withholding gastric acid suppression therapy in the setting of active or recent C difficile infection.