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Evidence of a relation between proton-pump inhibitors (PPIs) and risk for an initial episode of Clostridium difficile infection (CDI) is somewhat mixed but sufficient for the FDA to issue a warning. In this meta-analysis of 16 observational studies, researchers examined whether risk for recurrent CDI was higher in patients who took gastric acid suppressants (PPIs, histamine-2–receptor antagonists [H2RAs], or both) between initial and recurrent CDI episodes. Recurrent CDI was defined variably across studies as occurring within 30, 60, or 90 days after resolution of initial infection.
A remarkable 52% of 7700 patients with initial CDI were taking acid suppressants. Risk for recurrent CDI was significantly higher among those who used acid suppressants than among those who did not (22% vs. 17%; adjusted odds ratio, 1.52). In subgroup analyses, the association between acid suppressants and recurrent CDI was significant in studies in which only PPIs were used (OR, 1.66) but not in those that involved both PPIs and H2RAs (OR, 1.37).
Tariq R et al. Association of gastric acid suppression with recurrent Clostridium difficile infection: A systematic review and meta-analysis. JAMA Intern Med 2017 Mar 27; [e-pub]. (http://dx.doi.org/10.1001/jamainternmed.2017.0212)
Comment
Because some identified studies were not adjusted for clinical and demographic factors associated with CDI, risks attributed to PPIs could be overestimated due to confounding. Even so, the association between PPIs and recurrent CDI is strong enough that clinicians should avoid prescribing these drugs to patients with CDI (unless the patient has a strong indication for PPI therapy). Preferential use of H2RAs also might be considered for C. difficile–infected patients who have a strong indication for acid-suppressive therapy.