Clinical and treatment-related factors associated with poorer outcomes in Clostridioides difficile infection (CDI) have been identified, particularly among critically ill and immunocompromised patients.

Published in the Journal of Hospital Infection, the analysis sought to address limitations of existing CDI prognostic models, which often under-represent critically ill patients and fail to incorporate intensive care-specific risk factors.

A team at University Hospital Bochum retrospectively analysed 87 adults hospitalised with CDI at a tertiary academic care centre between 2012 and 2014. The mean age was 60.7 years, 48.3% of the cohort were aged 65 years or older, and 52.9% were immunosuppressed.

Nearly 70% acquired infection nosocomially, and 42.5% needed admission to the intensive care unit (ICU) or intermediate care (IMC).

The primary endpoint was major adverse clinical events in CDI (MACE-CDI), defined as surgery, in-hospital mortality, or a severe, complicated disease course. Secondary outcomes included recurrence, disease severity and length of stay.

Predictors of mortality and CDI recurrence

Overall, MACE-CDI occurred in 16.1% of patients, and in-hospital mortality was 13.8%. ICU/IMC admission was strongly associated with poorer outcomes, increasing the odds of MACE-CDI more than fourfold (odds ratio [OR] 4.26; 95% CI 1.29–16.76; P=0.017).

ICU/IMC admission was also associated with an almost ninefold increase in mortality (OR 8.89; 95% CI 2.15–60.65; P=0.0017).

Age was also an independent predictor of mortality, with significantly worse outcomes in patients older than 55 years. Within the ICU/IMC subgroup, an age of 65 years or older increased the likelihood of severe CDI by more than fivefold (OR 5.30; 95% CI 1.24–28.71; P=0.023).

CDI reoccurred in 21.8% of patients. Colonisation with vancomycin-resistant Enterococci (VRE) substantially increased the overall risk of recurrence (OR 6.09; P=0.048).

ICU/IMC patients colonised with VRE had a more than 16-fold increased likelihood of recurrence (OR 16.20; P=0.015).

Immunosuppression was also associated with recurrence in critically ill patients (OR 6.39; P=0.027).

Impact of antibiotic exposure and nutritional factors

Several antibiotic classes were associated with severe or nosocomial CDI. Cephalosporin exposure increased the risk of severe CDI more than fourfold, while carbapenem use was associated with nosocomial acquisition.

Piperacillin/tazobactam exposure was linked to both severe disease and nosocomial CDI, although paradoxically, it was associated with a lower risk of recurrence.

By contrast, trimethoprim/sulphamethoxazole appeared to be associated with lower CDI severity, which the authors suggested may reflect reduced disruption of the gut microbiota compared with broader-spectrum antibiotics.

Parenteral nutrition was associated with severe CDI and prolonged hospitalisation, extending admission by approximately 33 days.

Microbiome disruption and recurrent CDI risk

The authors noted the retrospective single-centre design, relatively small sample size and potential residual confounding as limitations. The dataset also predated newer CDI management approaches, including wider use of fidaxomicin and microbiota-directed therapies, they said.

Nevertheless, the authors concluded that the findings reinforce growing evidence linking microbiome disruption and colonisation by multidrug-resistant organisms to recurrent CDI risk, while also highlighting the multifactorial drivers of CDI severity in critically ill and immunocompromised patients.

The findings also support the need for more refined risk stratification, antimicrobial stewardship and preventive strategies in high-risk populations. However, prospective multicentre studies are still needed to validate the findings and inform future prognostic models, they added.

Reference
Nashtar MA et al. From ward to intensive care unit: clinical drivers of adverse outcomes in Clostridioides difficile infection – A retrospective cohort study. J Hosp Infect 2026;170:209–17.