Fidaxomicin for initial episode of Clostridioides difficile Infection reduces recurrence in immunocompromised hosts – a large retrospective cohort study

Introduction Fidaxomicin is a narrow-spectrum, non-absorbable antibiotic recommended as first-line therapy for non-fulminant Clostridioides difficile infection (CDI). While some studies suggest a reduction of recurrence for immunocompromised hosts (ICHs), the findings remain inconsistent and limited. We aimed to evaluate the clinical outcomes of fidaxomicin for a first CDI episode in ICHs within a large healthcare system. Methods We conducted a retrospective cohort study of Clalit Health Services adults with a first laboratory-confirmed CDI between January 2013 and December 2023. Patients with prior CDI were excluded. The primary outcome was a composite of recurrence, 90-day mortality, and colectomy, which were compared between the fidaxomicin and vancomycin groups. Secondary outcomes included each component individually. Results The study included 11,204 patients with a first CDI episode, of whom 2,362 were immunocompromised. The fidaxomicin group had a significantly lower recurrence rate compared to vancomycin (8% vs. 17%, p=0.019), while it was not associated with reduced composite outcome (aOR=0.65, CI95% 0.39-1.07, p=0.09). Multivariable analysis also confirmed a reduction in recurrence risk (aOR 0.44, 95% CI 0.21–0.96). Older age, previous antibiotic use within 90 days, and hypoalbuminemia were independently associated with worse outcomes, while recurrence was linked to increased long-term mortality. Conclusion ICHs treated with fidaxomicin had significantly lower recurrence rates and fewer complications compared to vancomycin. Despite assumptions, ICHs had recurrence rates similar to immunocompetent patients, highlighting the role of comorbidities and treatment choices. Our findings support fidaxomicin as a preferred first-line option in select ICHs and underscore the need for individualized management strategies to improve outcomes in this high-risk population