Common Drugs—Including Non-Antibiotics—Linked to Increased Risk of C. difficile Infection: Study
Sweden: A Swedish population-based case-control study found that both antibiotics and several commonly prescribed non-antibiotic medications are associated with a significantly increased risk of Clostridioides difficile infection.
Among non-antibiotic drugs, the highest risks were observed with antidiarrheals, analgesics, and corticosteroids. While antibiotics and acid-suppressing drugs are already well-known risk factors, this study highlights that other widely used medications may also contribute to infection risk.
The study, published in Gut by Annelies Boven and colleagues from the Karolinska Institutet, aimed to explore how a broad range of medications—particularly those that may influence the gut microbiome—affect the risk of developing C. difficile infection (CDI). Although antibiotics have long been recognized as a major driver of CDI, evidence regarding other drug classes has remained limited.
For this purpose, the researchers conducted a large population-based case–control analysis using linked Swedish national registries from 2006 to 2019. The study included 42,921 individuals diagnosed with CDI and 355,159 matched controls based on age and sex. Medication exposure within 30 days before diagnosis was assessed, and associations with CDI risk were evaluated using multivariable statistical models that accounted for comorbidities and concurrent drug use.
Key Findings:
- A strong association was observed between certain antibiotic classes and increased risk of Clostridioides difficile infection.
- Lincosamides were linked to the highest risk, followed by combinations of penicillins, sulfonamides with trimethoprim, and cephalosporins.
- Tetracyclines did not show a significant association with increased CDI risk, indicating variability across antibiotic classes.
- Several non-antibiotic medications were also associated with increased CDI risk.
- Antidiarrheal drugs showed the highest risk among non-antibiotic medications.
- Corticosteroids and proton pump inhibitors were also significantly associated with higher CDI risk.
- Other drug classes linked to increased risk included nervous system medications, constipation treatments, histamine H2-receptor antagonists, antidepressants, and beta blockers.
- Non-steroidal anti-inflammatory drugs did not demonstrate a significant association with CDI risk.
- Lipid-lowering medications and aspirin were associated with a modest reduction in CDI risk.
- The potential protective effects of these drugs require further investigation.
The study highlights the complex relationship between commonly prescribed medications and gut microbiome health. While antibiotics remain the primary contributors to CDI, the results suggest that other drugs frequently used in routine clinical practice may also play a meaningful role.
The authors emphasized that these findings support the need for careful and judicious prescribing practices. Recognizing the potential risks associated with both antibiotic and non-antibiotic medications could help clinicians make more informed decisions, particularly in patients at higher risk for CDI.
Overall, the study provides valuable insights for clinicians and policymakers, highlighting the importance of considering a wider range of medications when evaluating CDI risk and reinforcing ongoing efforts toward antimicrobial stewardship and safer prescribing strategies.
Reference:
Boven A, Vranken H, Vlieghe E, et alCommonly prescribed drugs as risk factors for Clostridioides difficile infections: a Swedish population-based case–control studyGut Published Online First: 31 March 2026. doi: 10.1136/gutjnl-2025-337629
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