Twenty-Five-Year Trends in Mortality Associated with Clostridioides difficile Infection Among Patients with Inflammatory Bowel Disease in the United States: A Population-Based Analysis of Demographic and Geographic Disparities

Background: Individuals with inflammatory bowel disease (IBD) are at substantially increased risk for Clostridioides difficile infection (CDI), which leads to significantly higher morbidity and mortality compared to the general population. However, comprehensive national-level analyses of long-term mortality trends in this population remain limited. This study examines mortality trends associated with IBD and CDI in the United States from 1999 to 2023. Methods: This descriptive study utilized the CDC WONDER Multiple Cause-of-Death database. Deaths involving IBD (ICD-10: K50, K51) and CDI (A04.7) were identified among adults aged 25 years and older. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated with 95% confidence intervals and stratified by sex, race/ethnicity, urbanization, and census region. Joinpoint regression was applied to estimate the annual percent change (APC) in mortality. Results: Between 1999 and 2023, 76,084 deaths were recorded. Medical facilities accounted for 46% of deaths, followed by decedents’ homes (28.3%) and nursing home/long-term care facilities (16.5%). Overall mortality declined gradually from 1999 to 2018 (APC: −0.23, p < 0.05), increased sharply through 2021 (APC: +12.75, p < 0.05), and was then followed by a non-significant change through 2023 (APC: −2.69; 95% CI: −8.24 to 3.19), consistent with a plateau. Men consistently exhibited higher AAMRs than women. Non-Hispanic White individuals had the highest AAMRs (1.844 in 2023), while Non-Hispanic Black individuals experienced a sustained increase from 2016 onward (APC: +7.11, p < 0.05). Hispanic mortality increased steadily throughout the study period (APC: +1.31, p < 0.05). Rural populations had higher overall AAMRs than urban populations. The Midwest recorded the highest regional AAMRs by 2023 (1.867). Conclusions: Mortality increased significantly between 2018 and 2021, coinciding with the COVID-19 pandemic, though our study design cannot prove causation. Disparities by race/ethnicity, urbanization, and region persisted. These findings underscore the need for ongoing antibiotic stewardship, equitable healthcare access, and targeted public health interventions for this vulnerable population.