S2057 Changing Trends in Clostridioides difficile Infection Mortality Among U.S. Adults: A CDC Analysis (1999–2023)

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Introduction: Clostridioides difficile infection (CDI) is a major cause of healthcare-associated diarrhea and colitis, particularly in hospitalized and elderly patients. The emergence of hypervirulent strains and rising antimicrobial resistance continue to drive high CDI-related mortality, particularly among older and medically complex individuals. This study evaluates national mortality trends and demographic disparities in CDI-related deaths in the U.S. from 1999 to 2023. Methods: Mortality data from 1999–2023 were obtained from the CDC WONDER database using International Classification of Diseases, Tenth Revision (ICD-10) codes for CDI. Age-adjusted mortality rates (AAMRs) per million were calculated using the 2000 U.S. standard population. Joinpoint regression identified trends and calculated Annual Percent Change (APC) and Average Annual Percent Change (AAPC). Analyses were stratified by sex, age, race/ethnicity, census region, urban-rural status, and state. Statistical significance was set at P < 0.05. Results: A total of 129,001 CDI-related deaths occurred in the U.S. over the 25-year period, with 78% occurring in inpatient settings. The overall AAMR rose 202% from 4.7 in 1999 to 14.2 in 2023 (AAPC: 5.1; 95% confidence interval [CI]: 4.4–6.1; P < 0.000001). Women had slightly higher AAMRs than men (23.3 vs 22.9) and a steeper increase (AAPC: 5.4 vs 5.1; both P < 0.000001). Adults aged ≥65 had a 3,863% higher AAMR than those aged 25–64 (107.0 vs 2.7), but the younger age group had a more rapid increase (AAPC: 8.4% vs 4.9%). Among racial groups, non-Hispanic Whites had the highest AAMR (24.4), while Hispanics had the steepest rise (AAPC: 6.3%; 95% CI: 5.1–7.9; P < 0.000001). Regionally, the Northeast had the highest mortality (AAMR: 26.1), but the South experienced the fastest growth (AAPC: 6.3%). Urban areas had a higher AAMR than rural areas (24.7 vs 22.0), yet rural areas showed a steeper rise (AAPC: 7.8% vs 5.7%). States in the top 90th percentile included Rhode Island, Maryland, Missouri, Ohio, and Kentucky. Conclusion: CDI-related mortality has more than tripled since 1999, disproportionately affecting older adults and those in inpatient settings. While urban areas had higher absolute rates, rural areas experienced sharper increases, suggesting disparities in healthcare access, antibiotic stewardship, and infection control. Notably, the rise among younger adults and Hispanic populations signals evolving epidemiologic patterns that warrant targeted surveillance, prevention, and early treatment strategies.

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