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Am J Gastroenterol. 2016 Nov;111(11):1641-1648. doi: 10.1038/ajg.2016.343. Epub 2016 Aug 30.

Proton Pump Inhibitors Do Not Increase Risk for Clostridium difficile Infection in the Intensive Care Unit.

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Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Biomedical Informatics, Columbia University Medical Center, New York, New York, USA.
Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
Hospital Epidemiology and Infection Control, NewYork-Presbyterian Hospital, New York, NY, USA.
Department of Epidemiology, Mailman School of Public Health, New York, New York, USA.
Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York, USA.



Patients in the intensive care unit (ICU) frequently receive proton pump inhibitors (PPIs) and have high rates of Clostridium difficile infection (CDI). PPIs have been associated with CDI in hospitalized patients, but ICU patients differ fundamentally from non-ICU patients and few studies have focused on PPI use exclusively in the critical care setting. We performed a retrospective cohort study to determine the associations between PPIs and health-care facility-onset CDI in the ICU.


We analyzed data from all adult ICU patients at three affiliated hospitals (14 ICUs) between 2010 and 2013. Patients were excluded if they had recent CDI or an ICU stay of <3 days. We parsed electronic medical records for ICU exposures, focusing on PPIs and other potentially modifiable exposures that occurred during ICU stays. Health-care facility-onset CDI in the ICU was defined as a newly positive PCR for the C. difficile toxin B gene from an unformed stool, with subsequent receipt of anti-CDI therapy. We analyzed PPIs and other exposures as time-varying covariates and used Cox proportional hazards models to adjust for demographics, comorbidities, and other clinical factors.


Of 18,134 patients who met the criteria for inclusion, 271 (1.5%) developed health-care facility-onset CDI in the ICU. Receipt of antibiotics was the strongest risk factor for CDI (adjusted HR (aHR) 2.79; 95% confidence interval (CI), 1.50-5.19). There was no significant increase in risk for CDI associated with PPIs in those who did not receive antibiotics (aHR 1.56; 95% CI, 0.72-3.35), and PPIs were actually associated with a decreased risk for CDI in those who received antibiotics (aHR 0.64; 95% CI, 0.48-0.83). There was also no evidence of increased risk for CDI in those who received higher doses of PPIs.


Exposure to antibiotics was the most important risk factor for health-care facility-onset CDI in the ICU. PPIs did not increase risk for CDI in the ICU regardless of use of antibiotics.

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Conflict of interest statement

Guarantor of the article: David M. Faleck, MD Specific author contributions: Conception and design: DMF, EYF, JAA, DEF. Data collection: DMF, HS, ELL, DEF. Analysis and interpretation: DMF, HS, JAA, DEF. Drafting the manuscript for important intellectual content: DMF, HS, EYF, ELL, JAA, DEF. All authors have approved the final manuscript. Potential competing interests: None.

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