Commonly prescribed drugs as risk factors for <i>Clostridioides difficile</i> infections: a Swedish population-based case–control study

BACKGROUND: infections (CDIs) are associated with antibiotic use, although the link with other drugs remains underexplored. OBJECTIVES: To investigate the association between antibiotic and non-antibiotic drugs with microbiome-modulating activity on new occurrences of CDI. DESIGN: We conducted a Swedish population-based case-control study from 2006 to 2019 including 42 921 cases matched with 355 159 population controls on age and sex, obtained from multiple linked Swedish registries. The effect of antibiotic and non-antibiotic use within 30 days from the index date on CDI occurrence was estimated using multivariable conditional logistic regression additionally with a lasso penalty. Models were adjusted for age and sex by design and for Charlson Comorbidity Index and concomitant drug use, providing adjusted ORs (aORs) with 95% CIs. RESULTS: Antibiotics with the greatest CDI risk were lincosamides (aOR=31.4, 95% CI 27.9 to 35.3), combinations of penicillins (aOR=19.8, 95% CI 15.9 to 24.5), sulfonamides and trimethoprim, and cephalosporins, though no association for tetracyclines. Among non-antibiotic drugs, we found decreased risks of CDI for lipid-modifiers (aOR=0.8, 95% CI 0.8 to 0.8) and aspirin (aOR=0.8, 95% CI 0.7 to 0.8) and increased risks for antidiarrhoeals (aOR=7.3, 95% CI 6.8 to 7.8), corticosteroids (aOR=2.4, 95% CI 2.3 to 2.5), proton-pump inhibitors (PPIs) (aOR=1.8, 95% CI 1.7 to 1.8), nervous system drugs, constipation drugs, histamine H2-receptor antagonists, antidepressants, and beta blockers, but no significant risk for non-steroidal anti-inflammatory drugs. CONCLUSIONS: We found varying effects of antibiotics on CDI, providing evidence for ongoing efforts in prudent prescribing decisions and antimicrobial stewardship. We confirmed PPI as a main risk factor for CDI and provided new evidence for other non-antibiotic drugs as potentially important risk factors considering their high prescription prevalence.