H2 antagonists linked to lower C. difficile risk than PPIs in intensive care

In a retrospective analysis of 15,462 critically ill patients, the use of histamine H2 receptor antagonists was associated with a lower risk of hospital-acquired Clostridioides difficile infection than the use of proton pump inhibitors. Among patients treated with H2 receptor antagonists, 2.6% developed C. difficile infection, compared with 3.4% among those treated with proton pump inhibitors. The matched odds ratio was 0.77, with a 95% confidence interval of 0.64–0.93 and a p-value of 0.006.

The investigators extracted data from the eICU Collaborative Research Database and MIMIC-IV for the study, which was published in BMC Infectious Diseases on 10 September 2026. Proton pump inhibitors and H2 receptor antagonists are commonly used in critically ill patients to prevent stress ulcers, but the relative risk of C. difficile infection associated with the two classes has been debated. The analysis specifically compared hospital-acquired C. difficile infection among intensive-care patients receiving the two treatments.

To improve comparability between the treatment groups, the researchers used propensity score matching to balance covariates. They compared clinical outcomes in the matched groups with chi-square tests and used multivariable logistic regression to identify factors associated with C. difficile infection, reporting odds ratios and 95% confidence intervals. Because this was an observational analysis, the results show an association rather than demonstrating that H2 receptor antagonists caused the lower infection risk.

Matching can also leave potential confounding from factors that were not adequately measured, recorded or represented in the matching process. The association between H2 receptor antagonist use and lower C. difficile infection risk was consistent across every subgroup evaluated: men and women; patients younger than 65 years and those aged 65 years or older; and patients with a body-mass index below 28 kg/m² and those with a body-mass index of at least 28 kg/m². The analysis also found that obesity, defined in the study by a body-mass index of at least 28 kg/m², was associated with a higher risk of infection.

Diabetes mellitus, kidney disease and the use of high-risk antibiotics were likewise associated with increased C. difficile infection risk. The findings provide additional evidence that the two classes of stress-ulcer treatments may have different associations with hospital-acquired C. difficile infection in critically ill patients. The analysis was limited to the population and data represented in the two databases and to the infection outcome examined.

Within those bounds, H2 receptor antagonist use was associated with a modestly lower risk of hospital-acquired C. difficile infection than proton pump inhibitor use among critically ill patients.

Subject of Research: Comparative observational risk of hospital-acquired C. difficile infection with H2 receptor antagonists and proton pump inhibitors in critically ill patients

Article Title: A comparison of the risk of hospital-acquired clostridioides difficile infection among critically ill patients treated with proton pump inhibitors and histamine H2 receptor antagonists

Article References: Guan, C., Chen, J., & Fang, L. (2026). A comparison of the risk of hospital-acquired clostridioides difficile infection among critically ill patients treated with proton pump inhibitors and histamine H2 receptor antagonists. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14387-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14387-z

Keywords: C. difficile infection, histamine H2 antagonists, proton pump inhibitors, intensive care, hospital-acquired infection, retrospective cohort study, propensity score matching, antibiotic exposure, odds ratio, critical illness, comparison, risk