Background: Clostridioides difficile infection (CDI) is a major cause of healthcare-associated diarrhoea with significant morbidity and mortality worldwide. In Germany, CDI incidence has declined in recent years. However, prospective multicentre data on all-cause in-hospital mortality among CDI patients and on risk factors for death remain scarce.

Methods: We conducted a prospective multicentre surveillance study in six German university hospitals between 2016 and 2020 to assess all-cause in-hospital mortality among CDI patients. Additionally, multivariable logistic regression was used to identify risk factors for death.

Results: A total of 3,592 CDI cases were recorded, of whom 46.7% were female. Overall all-cause in-hospital mortality was 11.7%, whereas CDI-attributable mortality was 0.4% (n = 16). Independent risk factors for death in CDI patients included increasing age (3% per year, aOR 1.03, 95% CI 1.02-1.04), longer hospital stay (1% per day, aOR 1.01, 95% CI 1.00-1.01), admission to internal medicine (aOR 1.60, 95% CI 1.32-1.94) or haematology-oncology (aOR 2.38, 95% CI 1.75-3.24) as proxies for patient complexity, and elevated creatinine levels within +/- 2 days of sampling (6% per mg/dl, aOR 1.06, 95% CI 0.99-1.13). In contrast, diagnosis on a general ward (versus ICU or intermediate care, irrespective of speciality) was associated with a lower risk of death (aOR 0.34, 95% CI 0.28-0.42).

Conclusions: Our study provides a comprehensive assessment of all-cause in-hospital mortality among CDI patients in Germany. By identifying robust and easily accessible risk factors for death, our findings support improved risk stratification and may inform targeted management strategies for high-risk patient populations.

Keywords: C. difficile; CDI; death; multicentre study; risk analysis.