Proton-Pump Inhibitors Raise Risk for C. difficile Infections

Allan S. Brett, MD


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In This Article

Abstract and Introduction


In two meta-analyses, PPI use was associated with a 1.7-fold higher risk for Clostridium difficile infection.


In February 2012, the FDA issued a safety alert regarding an association between proton-pump inhibitors (PPIs) and Clostridium difficile infection. In new meta-analyses, two groups of researchers used slightly different criteria to select studies in which this association could be evaluated; all included studies (23 and 42, respectively) were observational (cohort or case-control). Each meta-analysis involved roughly 300,000 patients.

In both meta-analyses, risk for C. difficile infection was significantly higher in PPI users than in nonusers (risk ratio, about 1.7). Although results across individual studies were heterogeneous, nearly all trended toward higher risk. Most of the included studies were adjusted for confounding variables, including antibiotic use. Concomitant use of both PPIs and antibiotics — examined in one meta-analysis — was associated with greater risk for C. difficile infection than was use of PPIs alone or antibiotics alone. Risk for C. difficile infection was higher with histamine (H)2-receptor antagonists than with no acid-suppressive therapy, but lower with H2-receptor antagonists than with PPIs.