The Impact of Hospital-Based Fidaxomicin Use Criteria on Clostridioides difficile Recurrence: A Retrospective Matched Cohort Study

Background/Objectives: Clostridioides difficile infection (CDI) is associated with substantial morbidity and high recurrence rates. Current guidelines recommend fidaxomicin over oral vancomycin due to reduced recurrence; however, its high acquisition cost limits widespread adoption. Our health system implemented criteria restricting fidaxomicin to patients with the highest risk for recurrence. This study evaluated the impact of this strategy on CDI recurrence and antimicrobial expenditures. Methods: We conducted a multicenter, retrospective matched cohort study across a rural health system from January 2023 through March 2026. The fidaxomicin criteria for use (intervention) went into effect on 1 January 2025. Adult hospitalized patients with an initial CDI episode treated with oral vancomycin and/or fidaxomicin were included. Patients with severe CDI or prior CDI episodes were excluded. A 2:1 matching algorithm based on key recurrence risk factors was used to compare pre-implementation (before criteria for use) and post-implementation (after criteria for use) cohorts. The primary outcomes were 28-day and 90-day CDI recurrences. Secondary outcomes included antimicrobial utilization and annualized expenditures. Results: A total of 144 matched patients were analyzed (96 control and 48 intervention). Fidaxomicin use decreased from 40.6% to 8.3% following implementation (p < 0.001). Annualized fidaxomicin expenditures declined by 54.7%. CDI recurrence rates were similar between groups: 28-day recurrence was 5.2% in the control group versus 6.2% in the intervention group, and 90-day recurrence was 7.3% versus 10.4%, respectively, with statistical non-inferiority at 28 days (p = 0.014). Conclusions: Implementation of risk-based fidaxomicin use criteria significantly reduced utilization and costs without a statistically significant increase in CDI recurrence. These findings support a targeted stewardship approach to optimize resource use while maintaining comparable clinical outcomes.