# P-1005. Real-World Effectiveness of Fidaxomicin in Preventing Recurrence of Initial Community-Associated Clostridioides difficile Infection

## TL;DR

This study finds that fidaxomicin is more effective than vancomycin in preventing recurrence of initial community-associated Clostridioides difficile infection in real-world outpatient settings.

## Contribution

The study provides real-world evidence supporting the IDSA guidelines that fidaxomicin is superior to vancomycin for initial community-associated CDI.

## Key findings

- Fidaxomicin was associated with lower recurrence rates at both 8 weeks and 90 days compared to vancomycin.
- The risk of recurrence was statistically significantly lower with fidaxomicin at 90 days.
- Results support the use of fidaxomicin as first-line treatment for initial community-associated CDI.

## Abstract

In 2021, ISDA guidelines recommended fidaxomicin over vancomycin as first line treatment of Clostridioides difficile infection (CDI) based on clinical trials showing reduced recurrence. However, real-world effectiveness studies of fidaxomicin primarily in hospitalized and high-risk populations showed mixed results. Evidence of fidaxomicin effectiveness for community associated (CA) CDI in outpatient settings remains limited. The study aim is to evaluate the real-world effectiveness of fidaxomicin for initial CA-CDI.

We used data from population-based surveillance of CDI in Monroe County, NY (2020-2024), as part of the CDC Emerging Infections Program. CA CDI was defined as a first episode with no healthcare exposure in the prior 12 weeks. Adults (≥ 18 years) who completed an uninterrupted course of oral therapy were included. Clinical data, inpatient treatment and recurrence at 8 weeks and 90 days were abstracted from medical records. Recurrence rates were compared between fidaxomicin and vancomycin treated groups using bivariate and multivariable log-binomial regression models.

Among 1193 cases with initial CA-CDI,146 (12.2%) received fidaxomicin and 1047 (87.8%) vancomycin. Groups were similar in sex, comorbidities and prior PPI/H2 blocker use. Cases receiving fidaxomicin were more likely to be aged 40-59 (32% vs. 23.3%). In hospital treatment was comparable (20.5% vs. 18.8%). Recurrence at 8 weeks and 90 days was 8.2% and 8.9% for fidaxomicin, and 14.9% and 17.8% for vancomycin, respectively (p < 0.05). Crude models showed that vancomycin was associated with a higher risk of 8-week recurrence (RR: 1.81; 95% CI: 1.03–3.18) and 90-day recurrence (RR: 2.00; 95% CI: 1.17–3.41). After adjustment, the risk remained elevated for 8-week recurrence (RR: 1.72; 95% CI: 0.98–3.03) and 90-day recurrence (RR: 1.89; 95% CI: 1.10 – 3.23).

Fidaxomicin was associated with a lower recurrence rate than vancomycin in CA-CDI with a statistically significant benefit at 90 days. These findings support the current IDSA guidelines and highlight the real-world advantage of fidaxomicin for initial CA-CDI management.

All Authors: No reported disclosures