Association between Proton Pump Inhibitor and Clostridioides Difficile risk in ICU patients: A Systematic review and meta-analysis of clinical outcomes
In brief
Proton pump inhibitors cut gastrointestinal bleeding risk by about 40% in ICU patients
A meta-analysis of eight studies involving roughly 58,000 critically ill adults found that stress-ulcer prophylaxis with PPIs lowered bleeding events by 40% compared with H2 blockers or placebo, while not changing Clostridioides difficile infection rates or overall mortality. The benefit came with high study heterogeneity and very low certainty, so further research is needed to confirm safety and impact on ICU stay.
- Journal
- Digestive diseases (Basel, Switzerland) (Q2)
- Published
- 16 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Abdul Rafeh Awan, Muniba Ijaz, Meher Ayyazuddin, Anoosh Farooqui, Puneet Kaur Bansal, Mudasar Nisar, et al.
- PMID
- 42461873
- DOI
- 10.1159/000553518
Why clinicians should know about it
- Picked for Critical Care and Intensive Care Medicine (top studies of the week, 19 July 2026): Recent Critical Care and Intensive Care Medicine research from a high-quartile journal.
- Picked for Gastroenterology (top studies of the week, 19 July 2026): SR of RCTs on PPI use and C. difficile risk
- Picked for Infectious Diseases (top studies of the week, 19 July 2026).
Abstract
BACKGROUND: Clostridioides difficile infection (CDI) is a leading cause of antibiotic-associated diarrhea in critically ill patients. This meta-analysis evaluated whether proton pump inhibitor-based stress ulcer prophylaxis increases CDI risk and examined associated outcomes, including mortality, gastrointestinal bleeding, and other clinical effects in ICU patients. METHODS: The study was prospectively registered on PROSPERO (CRD420251176540). Following PRISMA guidelines, PubMed, Scopus, Cochrane, and Google Scholar were searched (2007-March 2025) for randomized controlled trials (RCTs) and observational studies comparing PPIs with H2 receptor antagonists (H2RAs) or placebo in ICU patients. Data were pooled using a random-effects model, and heterogeneity was assessed using the I2 statistic. RESULTS: Eight studies (~58,000 patients) met inclusion criteria. PPI use did not significantly increase CDI risk (OR 1.12; p = 0.49, I2 = 73%) or mortality (RR 1.01; p = 0.70) but significantly reduced gastrointestinal bleeding risk (RR 0.60; p = 0.02), particularly versus H2RAs (RR 0.72; p = 0.0008). No significant differences were found in ICU or hospital length of stay as well as for mechanical ventilation duration. CONCLUSION: In ICU patients, PPI prophylaxis was associated with reduced gastrointestinal bleeding but showed no clear benefit for mortality, ICU or hospital length of stay, or duration of mechanical ventilation. The available evidence does not allow firm conclusions regarding CDI risk because of substantial heterogeneity and very low certainty of evidence. Compared with H2RAs, PPIs provide greater bleeding protection, although possible signals of longer ICU stay and slightly higher mortality require further investigation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.