Factors driving increases in Clostridioides difficile infection rates in England: A national case-control study, 2019 to 2024

Background: Numbers of Clostridioides difficile infections (CDI) in England have increased since 2021. The factors driving the increase are unknown. We aimed to understand the factors associated with CDI and what proportion of this recent increase could be explained by changes to these risk factors. Methods: Case-control study, with CDI case data linked to hospitalisation episodes. Control cases were non-CDI related hospitalisation episodes. A logistic regression model estimated odds ratios (ORs) for individual and regional demographic factors, comorbidities, testing rates and primary care antibiotic consumption. To assess temporal changes, the model was fitted to data from financial year 2019/20 and used to predict cases in 2020/21 onwards, compared to observed data. Results: Factors associated with testing positive for CDI were age, white ethnicity, comorbidities and primary care prescribing. The regions with the highest ORs were the North West and Yorkshire and Humber. Predicting cases using 2019/20 coefficients showed that demographic changes and antibiotic use explained 12.5% of the difference between observed cases and our baseline model in 2023/24. Including comorbidities and testing rates explained 63% of this increase. Conclusion: The strongest risk factors for CDI were age and antibiotic consumption. Increased hospitalisations, comorbidities and testing explained a large proportion of the rise in CDI cases whereas an ageing population, increases in antibiotic prescribing and demographic changes predicted smaller increases in CDI cases. However, the factors considered were not enough to fully explain the rise in cases and further investigation is needed into other factors that may be contributing.