Clostridium difficile infection (CDI) has become a significant healthcare issue with increasing morbidity and mortality in the US and Europe. Frailty, characterized by reduced physical reserves and resistance to stressors, is linked to poor outcomes but its impact on CDI patients remains underexplored. This study seeks to address this gap through a nationwide analysis.

Using the National Readmission Database from 2016 to 2020, we employed the International Classification of Diseases, 10th revision, Clinical Modifications codes to identify adult patients admitted with CDI. We further stratified CDI hospitalizations based on frailty. Utilizing a regression model, we assessed the impact of frailty on CDI outcomes.

We included 144,611 CDI patients of whom 98,167 (67.88 %) were frail. Multivariate analysis showed that frail CDI patients had significantly higher mortality (adjusted odds ratio (aOR) 4.87), acute kidney injury requiring dialysis (aOR 9.50), septic shock (aOR 14.23), and intensive care unit admission (aOR 6.80). CDI-specific complications were more likely in frail patients, including toxic megacolon (aOR 10.22), intestinal perforation (aOR 2.30), need for colectomy (aOR 3.90) and CDI recurrence (aOR 3.65). Resource utilization, indicated by hospitalization charges, length of stay, and 30-day readmission rates, was greater among frail patients.

Our study underscores the significant association between frailty and various critical endpoints of CDI, including its incidence, mortality, and recurrence. Additionally, frailty independently predicts higher resource utilization and elevated 30-day readmission. Recognizing frailty as a determinant of CDI outcomes can aid clinicians in risk stratification and guide tailored interventions for this population.