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Abstract

BackgroundClostridioides difficile infections (CDI) continue to cause substantial morbidity and mortality, with increasing incidence in some countries post-COVID-19. Recurrence affects 10-20% of CDI patients: whether risk factors have changed over time is unclear, particularly post-COVID-19. MethodsUsing electronic health records from hospitals in Oxfordshire, UK, including results from community samples, we estimated the incidence of CDI recurrence across different calendar periods between 2000-2025. To investigate whether risk factors had changed over time, we used interaction tests within multivariable Fine-Gray regression models (modelling death as a competing risk), using backwards elimination, starting from 39 risk factors identified from the literature. ResultsRecurrence occurred within 1-year in 12.6%, 12.5%, 10.8% and 13.1% of CDI cases in "high virulence" 2003-2008 (n=527), "post-high virulence" 2008-2012 (n=252), "pre-pandemic" 2012-2020 (n=143) and "post-pandemic" 2020-2025 (n=110) periods respectively. The only factor with evidence of variation in its association with recurrence over time was surveillance classification (heterogeneity p=0.019; others p>0.05). Compared with hospital-onset cases, community-onset community-associated cases had increasing recurrence risks over time (subdistribution hazard ratios (SHRs)=2.05 (95% CI 1.27-3.31) in "post-pandemic" and 1.86 (1.16-2.98) in "pre-pandemic"), especially compared to the "high virulence" era of the early 2000s (SHR=0.81 (0.56-1.16)). This heterogeneity persisted after adjusting for baseline blood tests as a marker of severity (heterogeneity p=0.022). ConclusionsCompared with hospital-onset hospital-associated cases, recurrence risks increased for community-onset community-associated CDI cases over time. Recurrence is a key contributor to overall CDI incidence and the underlying causes of increasing risks with community-onset community-associated cases should be explored further. Short summaryOver 2000-2025, risk of recurrence following Clostridioides difficile infection increased significantly for community-onset community-associated cases, compared to hospital-onset hospital-associated cases. Older age, hospital exposure, immunosuppression, chronic kidney disease, diverticular disease, enteral feeding and recent sepsis/bacteraemia were significantly associated with recurrence.

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