GutCommonly Prescribed Drugs as Risk Factors for Clostridioides difficile Infections: A Swedish Population-Based Case-Control Study

ℹ️ Observational Association-Only Evidence

A Swedish case-control study of 42,921 CDI cases and 355,159 controls identified multiple non-antibiotic drug classes as independent CDI risk factors, including PPIs, corticosteroids, antidepressants, and beta blockers. Lincosamides carried the highest antibiotic risk at aOR 31.4.

Clinical Considerations

• Lincosamides showed a 31-fold CDI risk and penicillin combinations a 20-fold risk, while tetracyclines showed no significant association.
• PPIs nearly doubled CDI risk (aOR 1.8), confirming a prior signal in a population-based design with concomitant drug adjustment.
• Corticosteroids (aOR 2.4) and antidiarrhoeals (aOR 7.3) emerged as substantial non-antibiotic contributors.
• Lipid-modifiers and aspirin showed modestly reduced CDI risk (aOR 0.8 each), an association that warrants mechanistic follow-up.

Practice Applications

• Consider CDI risk when prescribing lincosamides or broad-spectrum penicillin combinations, and reassess duration regularly.
• Review PPI continuation in patients without a current evidence-based indication.
• Recognize corticosteroids, antidepressants, and beta blockers as potential contributors when evaluating recurrent or unexplained CDI.
• Integrate medication review into CDI prevention, not only antimicrobial stewardship.

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