Original article
Alimentary tract
Prophylaxis for Stress Ulcers With Proton Pump Inhibitors Is Not Associated With Increased Risk of Bloodstream Infections in the Intensive Care Unit

https://doi.org/10.1016/j.cgh.2016.12.035Get rights and content

Background & Aims

Proton pump inhibitors (PPIs) have been associated with increased risk of infection, likely because of changes in intestinal epithelial permeability and the gastrointestinal microbiome. PPIs are frequently given to patients in the intensive care unit (ICU) to prevent stress ulcers. These patients are at risk for bloodstream infections (BSIs), so we investigated the relationship between PPI use and BSIs among patients in the ICU.

Methods

We performed a retrospective cohort study of adults (≥18 years) admitted to 1 of 14 ICUs within a hospital network of 3 large hospitals from 2008 through 2014. The primary exposure was PPI use for stress ulcer prophylaxis in the ICU. The primary outcome was BSI, confirmed by culture analysis, arising 48 hours or more after admission to the ICU. Subjects were followed for 30 days after ICU admission or until death, discharge, or BSI. Multivariable Cox proportional hazards modeling was used to test the association between PPIs and BSI after controlling for patient comorbidities and other clinical factors.

Results

We analyzed data from 24,774 patients in the ICU, including 756 patients (3.1%) who developed BSIs while in the ICU. The cumulative incidence of BSI was 3.7% in patients with PPI exposure compared with 2.2% in patients without PPI exposure (log-rank test, P < .01). After adjusting for potential confounders, PPI exposure was not associated with increased risk of BSI while in the ICU (adjusted hazard ratio, 1.08; 95% confidence interval, 0.91–1.29). Comorbidities, antibiotic use, and mechanical ventilation were all independently associated with increased risk for BSIs.

Conclusions

In a retrospective study of patients in the ICU, administration of PPIs to prevent bleeding was not associated with increased risk of BSI. These findings indicate that concern for BSI should not affect decisions regarding use of PPIs in the ICU.

Section snippets

Methods

The institutional review board of Columbia University approved this study.

Study Population

From 60,764 patients initially evaluated for the study, 24,774 patients met eligibility criteria and were included in the analysis. A total of 756 patients (3.1%) developed BSI between days 3 and 30 of ICU stay. The mortality rate during the index ICU admission was 19% among patients who developed BSIs compared with 7.7% among patients who did not develop BSIs (P < .01). The incidence rate of BSIs was similar throughout the 7 years of the study (P for trend = .26).

Characteristics at Baseline and During Treatment in the Intensive Care Unit

Patients who received

Discussion

Use of PPIs for stress ulcer prophylaxis in the ICU was not associated with increased risk for BSI, and this null finding was robust through multiple sensitivity analyses. If the relationship between PPIs and BSI was mediated by PPI-induced changes in intestinal permeability, one might expect that PPIs would increase risk for BSI from enteric but not from non-enteric bacteria. However, there was also no association between PPIs and risk for BSI with predominantly enteric organisms.

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    Conflicts of interest The authors disclose no conflicts.

    Funding Dr Freedberg was supported by a Research Scholar Award from the American Gastroenterological Association (AGA) and by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH) (KL2 TR000081, formerly KL2 RR024157). The views expressed in this article represent those of the authors and do not necessarily represent the views of the AGA or the NIH. This project was also funded in part by the grant Health Information Technology to Reduce Healthcare-Associated Infections (R01-NR010822, Elaine Larson).

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