Nonantibiotic Medications Contribute to CDI Risk

Clostridioides difficile infection (CDI) risk extends beyond antibiotic exposure to include several commonly prescribed nonantibiotic medications, according to a large Swedish population-based case–control study. The findings highlight the need for broader medication review when assessing CDI risk in clinical practice.

Investigators analyzed 42,921 CDI cases matched with more than 355,000 controls using national registry data from 2006 to 2019. Medication exposure within 30 days prior to infection was evaluated using multivariable models adjusted for comorbidities and concomitant drug use.

As expected, antibiotics carried the highest risk. Lincosamides were associated with the greatest CDI risk (adjusted odds ratio [aOR], 31.4), followed by combinations of penicillins (aOR, 19.8), sulfonamides with trimethoprim, and cephalosporins. No significant association was observed with tetracyclines.

Among non-antibiotic drugs, several classes were associated with increased CDI risk. Antidiarrheal agents showed a strong association (aOR, 7.3), followed by corticosteroids (aOR, 2.4) and proton pump inhibitors (PPIs) (aOR, 1.8). Additional associations were observed with nervous system medications, constipation therapies, histamine H2-receptor antagonists, antidepressants, and beta blockers. In contrast, lipid-modifying agents and aspirin were associated with reduced CDI risk.

The authors noted that “we found varying effects of antibiotics on CDI,” reinforcing the importance of antimicrobial stewardship. They also emphasized that the study “confirmed PPI as a main risk factor for CDI” and identified “other non-antibiotic drugs as potentially important risk factors considering their high prescription prevalence.”

Reference
Boven A, Vranken H, Vlieghe E, et al. Commonly prescribed drugs as risk factors for Clostridioides difficile infections: a Swedish population-based case–control study. Gut. Published Online March 31, 2026. doi: 10.1136/gutjnl-2025-337629