Proton pump inhibitors and risk for recurrent Clostridium difficile infection

Proton pump inhibitors (PPIs) are widely used gastric acid suppressants, but they are often prescribed without clear indications and may increase risk of Clostridium difficile infection (CDI). We sought to determine the association between PPI use and the risk of recurrent CDI.

Retrospective, cohort study using administrative databases of the New England Veterans Healthcare System from October 1, 2003, through September 30, 2008. We identified 1166 inpatients and outpatients with metronidazole- or vancomycin hydrochloride-treated incident CDI, of whom 527 (45.2%) received oral PPIs within 14 days of diagnosis and 639 (54.8%) did not. We determined the hazard ratio (HR) for recurrent CDI, defined by a positive toxin finding in the 15 to 90 days after incident CDI.

Recurrent CDI was more common in those exposed to PPIs than in those not exposed (25.2% vs 18.5%). Using Cox proportional survival methods, we determined that the adjusted HR of recurrent CDI was greater in those exposed to PPIs during treatment (1.42; 95% confidence interval [CI], 1.11-1.82). Risks among exposed patients were highest among those older than 80 years (HR, 1.86; 95% CI, 1.15-3.01) and those receiving antibiotics not targeted to C difficile during follow-up (HR, 1.71; 95% CI, 1.11-2.64). [corrected]

Proton pump inhibitor use during incident CDI treatment was associated with a 42% increased risk of recurrence. Our findings warrant further studies to examine this association and careful consideration of the indications for prescribing PPIs during treatment of CDI.