Proton Pump Inhibitors and the Risk for Hospital-Acquired Clostridium difficile Infection

Abstract

Objective: To examine the relationship between proton pump inhibitor (PPI) usage and nosocomial Clostridium difficile infection (CDI) and determine the duration of therapy at which CDI risk increases.

Patients and methods: This retrospective case-control study included consecutive adult patients in whom nosocomial CDI developed after hospitalization for 3 or more days at one of 2 affiliated hospitals between June 1, 2010, and October 31, 2011. These patients were matched to patients hospitalized within 6 months who did not have CDI development in a 1:2 ratio using age, sex, and antibiotic usage. Potential risk factors for CDI, including PPI use and duration, were evaluated. Multivariate analysis was performed to control for confounding variables and identify risk factors.

Results: A total of 201 patients were evaluated, 67 with CDI and 134 matched controls. Patients in whom CDI developed were more likely to have received a PPI (76% vs 39%; P<.001) and had a longer duration of PPI therapy (median [range], 5 [0-20] days vs 0 [0-11] days; P<.001) than those who did not have CDI development. After controlling for prior hospital admission, intensive care unit admission, admission from a skilled nursing facility, immunosuppression, number of antibiotics received, PPI duration, and time to event via multivariate analysis, PPI duration was found to be a risk factor for CDI (odds ratio, 1.14; 95% CI, 1.02-1.27; P=.018). The probability for CDI was higher when PPI use exceeded 2 days in patients without a prior hospital admission and 1 day in patients with a prior admission.

Conclusion: The duration of PPI therapy is significantly associated with CDI. Clinicians should strongly consider restricting PPI use given the short exposure time associated with this increased risk.

Keywords: CDI; Clostridium difficile infection; H2RA; ICU; OR; PPI; SUP; histamine 2 receptor antagonist; intensive care unit; odds ratio; proton pump inhibitor; stress ulcer prophylaxis.