S2064 Increased Risk of Clostridioides difficile Infection in Adults With Prior Appendectomy: A Propensity Score-Matched Analysis

Introduction: Historically considered vestigial, the vermiform appendix is now understood to play a role in maintaining gut microbiota homeostasis and mucosal immunity. Its removal may disrupt the intestinal microbial reservoir and immune surveillance, potentially predisposing individuals to gastrointestinal infections, including Clostridioides difficile infection. This study aimed to evaluate whether a history of appendectomy is associated with an increased risk of C. difficile infection in adults. Methods: Using the TriNetX global health research network, which aggregates electronic medical records from 95 healthcare organizations, we conducted a retrospective cohort study of adults aged 18–65 who underwent a general medical examination. Two cohorts were created: those with a history of appendectomy (Cohort 1, n = 106,712) and those without (Cohort 2, n = 3,272,219). Patients with underlying conditions known to increase C. difficile risk—including inflammatory bowel disease, immunosuppression, and recent antibiotic use—were excluded. Propensity score matching (1:1) was performed based on age, sex, and age at the index event, resulting in 2 well-balanced cohorts (n = 106,466 each). The primary outcome was the incidence of C. difficile infection as identified by International Classification of Diseases, Tenth Revision (ICD-10) codes A04.7 and B96.89. Analyses included risk comparison, Kaplan-Meier survival estimates, and count-based outcome frequency. Results: C. difficile infection occurred in 0.7% of the appendectomy group compared to 0.2% of the control group, corresponding to a risk difference of 0.5% (95% confidence interval [CI]: 0.4–0.5, P< 0.001). The appendectomy cohort exhibited a significantly increased risk of infection (risk ratio: 3.01; odds ratio: 3.02). Kaplan-Meier survival analysis revealed a lower C. difficile–free survival probability in the appendectomy group (97.86% vs 98.86%, log-rank P < 0.001), with a hazard ratio of 2.46 (95% CI: 2.12–2.85). Additionally, the mean number of C. difficile episodes was higher in the appendectomy cohort (0.012 vs 0.003, P < 0.001). Conclusion: Adults with prior appendectomy demonstrate a significantly higher risk of developing C. difficile infection compared to matched controls without appendectomy, even after controlling for major confounders. These findings highlight the immunological importance of the appendix in maintaining colonic microbial balance and suggest the need for heightened clinical awareness in this population, particularly in settings with elevated risk for nosocomial infections or antibiotic exposure.