Risk Factors for Healthcare-Associated Clostridioides difficile Infection: A Systematic Review

Objectives: This systematic review sought to identify and synthesize the key patient-related, clinical and healthcare-associated risk factors for Clostridioides difficile infection (CDI), with a special interest in recurrent CDI. Methods: A systematic literature search identified studies investigating risk factors for CDI and recurrent CDI. The study consisted of twenty studies published from 2012 to 2025. Study characteristics, demographic factors, comorbidities, underlying diseases, healthcare exposures and CDI recurrence/recurrence were extracted and compared between different studies. Results: The study revealed that CDI is associated with several interdependent risk factors like older age, prior CDI, other hospitalization and intensive care unit admission (ICU), severe underlying disease and immunosuppression were the factors most commonly associated with an increased risk. Notable associations were also seen with malignancy, hematological malignancy, inflammatory bowel disease, chronic kidney disease, gastrointestinal disease, diabetes mellitus, cardiovascular disease, chronic pulmonary disease and chronic liver diseases. Recent surgery, chemotherapy, haematopoietic stem-cell transplantation, corticosteroid therapy, immunomodulatory treatment and renal replacement therapy were also identified as potential contributors. Previous CDI was most closely linked to recurrence, underscoring need for post-infection monitoring and preventive measures. Conclusions: The multifactorial etiology of CDI demonstrated in this systematic review reinforces the importance of patient susceptibility, disease, healthcare exposure, and prior infection. Advanced age, previous CDI, prolonged hospitalization, severe illness by the APACHE II score, immunosuppressive states malignancy and inflammatory bowel disease are relevant candidates for stratification of risk.