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

Abstract

Background & Aims Proton pump inhibitors (PPIs) have been associated with increased risk of infection, likely due to 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 hrs 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 to 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% CI, 0.91–1.29). Comorbidities, antibiotic use, and mechanical ventilation were all independently associated with increased risk for BSIs. Conclusion 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.

The impacts of acid suppression on duodenal microbiota during the early phase of severe acute pancreatitis

“…Pneumonia was the most common infections in this study, which might due to the higher incidence of acute lung injury or acute respiratory distress syndrome (75-82%) in the study and the treatment of mechanical ventilation. Similar results also showed that PPI inhibitors were not associated with an increased risk of bloodstream infections in the intensive care unit 23 . Although the actual clinical problems were not serious, the theoretical risk of SIBO/DBO or SAP aggravation due to duodenal dysbiosis remains not to be ignored.…”

Role for diet in normal gut barrier function: developing guidance within the framework of food-labeling regulations

“…Animal studies indicate that both TGR5 and FXR contribute to the integrity of the intestinal barrier (32, 48, 69, 94). Alternatively, some bile acids exert direct, receptor-independent toxicity toward intestinal epithelial cells (34), based on the detergent properties of bile acids (149), induction of apoptosis (3), and induction of changes in tight junction proteins (171). Finally, some unconjugated bile acids may provoke colonic mucus secretion, probably through a direct action on mucus-secreting cells.…”

“…However, capsule endoscopy revealed exacerbation of NSAID-induced small bowel injury by a PPI (rabeprazole) in 57 healthy subjects (226). In contrast, use of a PPI was not associated with incidence of bloodstream infections in the intensive care unit (data from 24,774 patients), suggesting that PPIs do not meaningfully alter permeability (34).…”

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

“…Since their release in the late 1980s, PPIs have become some of the most widely prescribed agents both in outpatient and inpatient settings throughout the world[ 44 - 53 ], with sales totalling billions dollars worldwide[ 54 , 55 ]. These drugs have proven effective in the treatment of ulcer disease (including bleeding peptic ulcer), gastroesophageal reflux disease, Helicobacter pylori (in combination with antibiotics), Zollinger-Ellison syndrome, in the prophylaxis of upper gastrointestinal complications with nonsteroidal anti-inflammatory drugs (NSAIDs) therapy, stress ulcer prophylaxis in ICU patients, and functional dyspepsia[ 50 , 53 , 56 - 60 ]. The widespread use of PPIs during the last 25 years in clinical practice is the result not only of their high efficacy but also of their excellent safety profile, proving to be one of the safest class of medication used in gastroenterology[ 57 , 61 - 64 ].…”