Trends and Disparities in Clostridioides difficile Infection Mortality in the United States From 1999 to 2020: A Nationwide Perspective

Background Clostridioides difficile infection (CDI) is one of the most prevalent infections in the United States, with rising mortality and disease severity in the early 2000s, followed by a steady decline after 2010. This study analyzes national trends in CDI mortality across different demographic and regional groups from 1999 to 2020. Methods We used CDC WONDER (Wide‐ranging Online Data for Epidemiologic Research) to analyze CDI‐related deaths among adults aged ≥ 35 years. Age‐adjusted mortality rates (AAMRs) per 100,000 individuals, along with annual percent change (APC) and average annual percent change (AAPC), were calculated and stratified by year, sex, race, and region. Statistical significance was assessed using Joinpoint regression analysis. Results During the study period, 191,653 CDI‐related deaths were reported. The AAMR for CDI‐related mortality increased from 1.1 in 1999 to 7.3 in 2011 (AAPC: 33.60). However, from 2011 to 2020, there was a notable decline in CDI mortality (AAPC: −10.48; 95% CI: −13.31 to −7.52). Mortality increased significantly with age, and females had a higher total number of deaths, while males maintained a higher AAMR throughout the study period. Among different racial groups, non‐Hispanic White individuals recorded the highest AAMR (6.1) in 2011, while Asian individuals had the lowest AAMR (2.3). Geographically, the Northeastern census region reported the highest AAMR (4.8) in 2008, while the Southern census region had the lowest AAMR (3.1). The majority of CDI‐related deaths (78%) occurred in hospitals, with nursing homes accounting for 17.7% of fatalities. Conclusions The sharp decline in CDI mortality starting in 2010 aligns with the implementation of strict guidelines and collaborative efforts between professional societies (IDSA/SHEA), the ACG, and government agencies (CDC). This underscores the success of coordinated public health initiatives in reducing healthcare‐associated infections and improving patient outcomes. However, disparities in mortality rates persist across different age, sex, ethnic, and geographic groups, emphasizing the need to further study disease trends and explore strategies to address these disparities in high‐risk populations.