Common Drugs and Clostridioides difficile Infection: Gut | July 2026

Introduction:

Antibiotic exposure is the best-established risk factor for Clostridioides difficile infection (CDI). However, the contribution of many commonly prescribed non-antibiotic medications has remained uncertain. This large Swedish population-based study evaluated the association between a wide range of medications and the risk of developing CDI.

Why was this study needed?

As polypharmacy becomes increasingly common, especially among older adults, understanding which medications influence CDI risk is essential for preventing avoidable infections and promoting safer prescribing practices.

What did the study show?

• Lincosamides (particularly clindamycin) carried the highest risk of CDI, followed by broad-spectrum penicillins, cephalosporins, and trimethoprim-sulfamethoxazole.
• Tetracyclines were not associated with an increased CDI risk.
• Among non-antibiotic medications, antidiarrheals showed the strongest association with CDI.
• Corticosteroids and proton pump inhibitors (PPIs) were independently associated with increased CDI risk.
• Higher CDI risk was also observed with H2-receptor antagonists, antidepressants, nervous system drugs, constipation medications, and beta-blockers.
• Lipid-lowering agents (mainly statins) and aspirin were associated with a modest reduction in CDI risk.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) were not associated with an increased CDI risk.

Clinical Impact:

Beyond antibiotic stewardship, clinicians should regularly review non-antibiotic medications that may increase CDI risk, particularly in elderly patients, hospitalized individuals, and those receiving multiple medications. Judicious use of PPIs, corticosteroids, and antidiarrheals may help reduce preventable CDI.

Take-Home Message:

CDI risk extends beyond antibiotics. Careful medication review—including PPIs, corticosteroids, antidiarrheals, and other commonly prescribed drugs—should become an integral part of CDI prevention, especially in patients with multiple risk factors or polypharmacy.