S2131 Nationwide Analysis of Mortality Trends in Enterocolitis Due to Clostridioides difficile From CDC WONDER Database and ARIMA Analysis (1999-2040)

Introduction: Clostridioides difficile infection (CDI) remains a leading cause of healthcare-associated gastrointestinal illness in the United States, particularly among older adults. This study aims to assess mortality patterns for CDI-related enterocolitis in U.S. adults aged ≥45 years from 1999 to 2023. Methods: We conducted a retrospective analysis using CDC WONDER single cause-of-death data from 1999 to 2023, in individuals aged ≥45 years with enterocolitis due to C. difficile (International Classification of Diseases, Tenth Revision code A04.7) as the underlying cause of death. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 population in gender, race, Hispanic origin, states, and 2013 urbanization framework. Joinpoint regression (JPR) was used to estimate trends through annual percent change (APC) with 95% confidence intervals. Autoregressive Integrated Moving Average (ARIMA: 4,0,0) approach was applied to predict annual AAMRs till 2024, followed by the Ljung-box test for validation of model. Results: Enterocolitis claimed 127,813 lives from 1999 to 2023, with the overall AAMR of 6.55 which is estimated to rise to 7.15 (95% confidence interval [CI]: 1.91-12.39; Ljung-box test P-value = 0.358) till 2040. The highest APCs were observed between 1999–2005, with men showing an APC of 35.57 (95% CI: 31.29–43.74, P = 0.00) and women 36.70 (95% CI: 32.60–42.19, P = 0.00). From 2016 to 2023, both Hispanic and Non-Hispanic populations exhibited significant declines in mortality trends, with APCs of –15.45 (95% CI: –19.73 to –12.83, P = 0.00) and –16.06 (95% CI: –30.87 to –8.11, P = 0.007), respectively. Among U.S. Census regions, Region 3 South exhibited the highest increase in mortality from 1999–2002 (APC: 63.35, 95% CI: 45.13–123.89, P = 0.00), followed by the steepest decline in later years (APC: –17.00, 95% CI: –19.72 to –14.94, P = 0.000). Among racial groups, American Indians showed the most significant decline from 2016–2023 (APC: –17.14, 95% CI: –31.21 to –10.55, P = 0.00). Across all 2013 urbanization categories, mortality rates increased from 1999–2005 with APCs ranging from 31.44 to 40.92, followed by a consistent decline in subsequent years, with APCs ranging from –0.58 to –7.58. Conclusion: Mortality from C. difficile enterocolitis has significantly fluctuated over the past 25 years. Despite improvements, disparities persist across race, sex, and region. Sustaining current control measures and strengthening targeted prevention efforts are essential to maintain progress and close existing gaps.