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

Faleck, David M MD1; Salmasian, Hojjat MD, MPH2; Furuya, Yoko E MD, MS3,4; Larson, Elaine L PhD, RN5; Abrams, Julian A MD, MS5,6; Freedberg, Daniel E MD, MS6

American Journal of Gastroenterology: November 2016 - Volume 111 - Issue 11 - p 1641–1648
doi: 10.1038/ajg.2016.343

Objectives: Patients in the intensive care unit (ICU) frequently receive proton pump inhibitors (PPIs) and have high rates ofClostridium difficileinfection (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.

Methods: 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 theC. difficiletoxin 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.

Results: 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.

Conclusions: 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.

1Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA

2Department of Biomedical Informatics, Columbia University Medical Center, New York, New York, USA

3Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA

4Hospital Epidemiology and Infection Control, NewYork-Presbyterian Hospital, New York, NY, USA

5Department of Epidemiology, Mailman School of Public Health, New York, New York, USA

6Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York, USA

Correspondence: David M. Faleck, MD, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, Box 1069, New York, New York 10029, USA. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received 10 March 2016; accepted 25 July 2016

Guarantor of the article: David M. Faleck, MD.

Specific author contributions: Conception and design: D.M.F., E.Y.F., J.A.A., and D.E.F.; data collection: D.M.F., H.S., E.L.L., and D.E.F.; analysis and interpretation: D.M.F., H.S., J.A.A., and D.E.F.; drafting the manuscript for important intellectual content: D.M.F., H.S., E.Y.F., E.L.L., J.A.A., and D.E.F. All authors have approved the final manuscript.

Financial support: Freedberg was supported by a Research Scholar Award from the American Gastroenterological Association and by the National Center for Advancing Translational Sciences, National Institutes of Health (KL2 TR000081, formerly KL2 RR024157). Data were obtained, in part, through the project Health Information Technology to Reduce Healthcare Associated Infections (NIH-R01NR010822 to Larson). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Potential competing interests: None.

© The American College of Gastroenterology 2016. All Rights Reserved.
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