C diff Treatment: Fidaxomicin's Rise as The Preferred Therapy Post-IDSA Guidelines

The 2021 update to the Infectious Diseases Society of America (IDSA) guidelines recommended fidaxomicin as the preferred treatment for Clostridioides difficile infection (CDI). In a study published in Open Forum Infectious Diseases, 45,049 hospitalized CDI patients from 779 US hospitals showed that fidaxomicin was associated with a lower recurrence rate (6.1% vs. 10.2%) and a higher sustained clinical response (91.7% vs. 87.8%) compared to vancomycin (P < .001 for both).

“In the propensity-matched results, we observed a more favorable sustained response (OR, 1.48; 95% CI, 1.11–1.97) and a lower CDI recurrence rate associated with fidaxomicin (OR, .61; 95% CI, .44–.85),” according to the investigators.¹

In 2021, the IDSA and SHEA introduced three new evidence-based guidelines for treating adult CDI. Developed by a multidisciplinary panel, these recommendations focused on treatments for initial and recurrent CDI episodes, incorporating new data on fidaxomicin and bezlotoxumab. The guidelines were based on a systematic review of evidence and assessed the benefits and harms of various treatment options using the GRADE approach.²

This retrospective observational study utilized the PINC AI Healthcare Database to analyze adult patients who received CDI treatment from January 2020 to June 2021 (pre-guideline update) and October 2021 to September 2022 (post-guideline update). The study investigated treatment patterns involving fidaxomicin, vancomycin, and metronidazole, along with clinical outcomes and healthcare resource utilization for patients treated exclusively with fidaxomicin versus those treated with vancomycin.

“Notably, fidaxomicin use significantly varied by census region and other hospital characteristics like number of beds,” according to investigators. “After controlling for hospital and patient characteristics, about a third of the variance in fidaxomicin use not explained by these factors was attributable to differences between hospitals.”¹

Comparing the pre- and post-guideline update periods, the proportion of patients treated with fidaxomicin increased from 5.9% to 13.7% (P < .001), while vancomycin use decreased from 87.9% to 82.9% (P < .001) and metronidazole use declined from 21.6% to 17.2% (P < .001). There was no significant difference in 90-day post-discharge costs between the two groups. The sensitivity analysis yielded similar results.

“Moreover, our findings consistently show that postindex costs were not statistically different between fidaxomicin and vancomycin either in the hospital or postdischarge within the first 90 days, and among patients with recurrent CDI fidaxomicin was associated with lower costs,” according to investigators.¹

The PINC AI Healthcare Database primarily includes hospitals from the US South, raising questions about the generalizability of the findings, despite covering about 25% of US hospitals. Additionally, unmeasured confounding factors may influence the results, although they align with findings from other studies, including randomized controlled trials. The research focuses on hospitalized patients with CDI, and comparing fidaxomicin to vancomycin or metronidazole in specific subgroups, such as those over 65, immunocompromised, or intensive care, was beyond the study's scope. Limited research suggests that fidaxomicin's benefits continue in these subgroups, though cost and treatment outcomes may vary.

Nearest-neighbor propensity matching and hierarchical regression methods were employed for the analysis. A sensitivity analysis was conducted to reassess the fidaxomicin versus vancomycin comparisons in patients with recurrent and non-recurrent index infections.

This 2021 update was prompted by the 2017 IDSA guideline update, which led to increased vancomycin use and a decrease in metronidazole use for treating CDI, while fidaxomicin usage remained low. Despite the guideline changes recommending vancomycin or fidaxomicin as first-line treatments, a study analyzing Medicare claims data from 2016 to 2018 found no improvement in clinical outcomes. Specifically, sustained response rates decreased, and recurrence rates increased after the guideline update. The authors suggest that while vancomycin was prescribed more frequently, it did not lead to better outcomes compared to metronidazole, and they highlight the potential benefits of increasing fidaxomicin use, given its improved efficacy in previous studies.³

These findings emphasize the importance of adopting fidaxomicin as a first-line treatment for CDI in hospitalized patients. Healthcare providers should consider fidaxomicin’s advantages over traditional therapies, particularly its association with lower recurrence rates and no increase in post-discharge costs.

References

1. Erik R Dubberke, Qinghua Li, Engels N Obi, Vladimir Turzhitsky, Fakhar Siddiqui, Brian H Nathanson, A Retrospective Assessment of Guideline Adherence and Treatment Outcomes From Clostridioides difficile Infection Following the IDSA 2021 Clinical Guideline Update: Clostridioides difficile Infection, Open Forum Infectious Diseases, Volume 11, Issue 10, October 2024, ofae524, https://doi.org/10.1093/ofid/ofae524 

2. Stuart Johnson, Valéry Lavergne, Andrew M Skinner, Anne J Gonzales-Luna, Kevin W Garey, Ciaran P Kelly, Mark H Wilcox, Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults, Clinical Infectious Diseases, Volume 73, Issue 5, 1 September 2021, Pages e1029–e1044, https://doi.org/10.1093/cid/ciab549

3. Parkinson, J. Updated CDI Treatment Guidelines Change Prescribing Therapy. Contagion. September 30, 2021. Accessed October 2, 2024.https://www.contagionlive.com/view/updated-cdi-treatment-guidelines-change-prescribing-therapy