Classical Risk Factors for Clostridioides difficile Infection in Hospitalized Patients: Frequency and Outcome Associations in a Tertiary Hospital in Madrid

Introduction. Clostridioides difficile infection (CDI) remains the leading cause of healthcare-associated diarrhea in developed countries and poses a major public health challenge due to its associated morbidity and mortality. This study aimed to describe the frequency of classical CDI risk factors and to characterize the clinical and epidemiological features of hospitalized CDI patients in a tertiary hospital in Madrid. A secondary exploratory objective was to examine associations between these factors and clinical outcomes. Methods. A retrospective observational cohort study was conducted, including all adults admitted to Alcorcón Foundation University Hospital between May 2020 and January 2024 with a first microbiologically confirmed CDI episode. Demographic, epidemiological, and clinical variables were analyzed. Associations between potential risk factors and outcomes (severe disease, intensive care unit [ICU] admission, prolonged length of stay, recurrence, and all-cause one-year mortality) were assessed using multivariable logistic regression models. Results. A total of 237 patients were included (45.1% female, median age 80.1 years). Prior hospitalization (70.0%), antibiotic exposure (73.4%), and proton pump inhibitor (PPI) therapy (69.6%) were frequent. Severe episodes occurred in 16.0% of patients, recurrence in 17.3%, and one-year mortality reached 33.3%. In multivariable analysis, antibiotic exposure, prior hospitalization, and PPI use were not independently associated with the studied outcomes. Age ≥ 80 years was associated with lower odds of ICU admission (adjusted odds ratio [aOR] 0.09, 95% confidence interval [CI] 0.02–0.42). Institutionalization was associated with increased one-year mortality (aOR 2.59, 95% CI 1.18–5.65), and a Charlson Comorbidity Index ≥ 3 was associated with prolonged length of stay (aOR 1.94, 95% CI 1.02–3.66) and higher one-year mortality (aOR 3.10, 95% CI 1.67–5.73). Conclusions. Classical CDI risk factors were highly prevalent, but most were not independently associated with adverse clinical outcomes after adjustment. Institutionalization and higher comorbidity burden were associated with worse prognosis, likely reflecting underlying frailty and multimorbidity rather than direct causal effects. These findings support further evaluation of measures of clinical vulnerability in CDI prognostic assessment.