Do the types and routes of proton pump inhibitor treatments affect clostridium difficile in ICU patients? A retrospective cohort study.

Background: : Proton pump inhibitors (PPI) are associated with Clostridium difficile infection (CDI). Impact of the route of administration is unknown.Research Design and Methods: Patients in Multiparameter Intelligent Monitoring in Intensive Care II database (MIMIC-II) from 2001 to 2008, >18 years old, admitted to medical, surgical, or cardiac ICUs were included. PPI exposures were omeprazole, esomeprazole, lansoprazole, and pantoprazole. PPI administration routes were oral or intravenous. Patients who received histamine receptor antagonists (H2RA) were the control arm. CDI was identified using ICD-9 diagnostic code 008.45. Multiple logistic regression analysis was performed to calculate odds ratios (OR).Results: The study included 16,820 patients (57% male) with a mean age of 63 (SD±17) years and hospitalization duration of 10.2 days (SD±11). Pantoprazole was the most common PPI (94%). CDI occurred in 2.4% and more in patients receiving PPIs than H2RAs (3.0% vs. 0.8%, p < 0.001). CDI prevalence increased with intravenous (95%CI = 1.69-3.39, OR 2.4) and oral (95%CI = 1.59-3.27, OR 2.3) PPI use compared to H2RAs. CDI prevalence was not associated with PPI route in the multivariable model (OR 1.07, 95%CI 0.86-1.34).Conclusions: Both intravenous and oral PPI use in the ICU were independently associated with CDI.