From the Guidelines
For first recurrent Clostridioides difficile infections, fidaxomicin (Dificid) is recommended over extended-dose vancomycin regimens due to its higher sustained clinical cure rates and lower rates of second recurrences, as suggested by the most recent guidelines from the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1.
Treatment Outcomes
The treatment outcomes of first recurrent Clostridioides difficile infections treated with Dificid (fidaxomicin) vs extended dosing of vancomycin can be compared based on several studies.
- Fidaxomicin typically results in higher sustained clinical cure rates (approximately 70-80% versus 50-60% with vancomycin) and lower rates of second recurrences.
- The standard fidaxomicin regimen is 200 mg twice daily for 10 days, while extended vancomycin regimens often involve 125 mg four times daily for 10-14 days, followed by a tapered and/or pulsed schedule over several weeks.
- Fidaxomicin's superior outcomes are likely due to its narrow spectrum of activity that preserves gut microbiota, its ability to kill C. difficile spores, and its prolonged presence in the gut, as noted in the guidelines 1.
Comparison of Studies
- A study from 2021 provides a conditional recommendation for using fidaxomicin over vancomycin for patients with recurrent CDI episodes, with low certainty of evidence 1.
- Another study from 2020 provides a weak recommendation for using fidaxomicin when treating patients with first recurrent CDI, based on limited evidence 1.
- Earlier studies from 2014 also compare the treatment outcomes of fidaxomicin and vancomycin, but the most recent guidelines from 2021 should be prioritized 1.
Clinical Considerations
- Both medications are generally well-tolerated, with similar safety profiles.
- However, fidaxomicin is significantly more expensive than vancomycin, which may influence treatment decisions.
- For patients with multiple recurrences or severe disease, consultation with infectious disease specialists is recommended to consider additional options such as fecal microbiota transplantation or bezlotoxumab.
From the FDA Drug Label
The results for clinical response at the end of treatment in both trials, shown in Table 6, indicate that DIFICID is non-inferior to vancomycin based on the 95% confidence interval (CI) lower limit being greater than the non-inferiority margin of -10% The results for sustained clinical response at the end of the follow-up period, also shown in Table 6, indicate that DIFICID is superior to vancomycin on this endpoint Since clinical success at the end of treatment and mortality rates were similar across treatment arms (approximately 6% in each group), differences in sustained clinical response were due to lower rates of proven or suspected CDAD during the follow-up period in DIFICID patients Table 6: Clinical Response Rates at End-of-Treatment and Sustained Response at 25 days Post-Treatment in Adult Patients Clinical Response at End of TreatmentSustained Response at 25 days Post-Treatment DIFICID % (N)Vancomycin % (N)Difference (95% CI)DIFICID % (N)Vancomycin % (N)Difference (95% CI)
- Confidence interval (CI) was derived using Wilson's score method Approximately 5%-9% of the data in each trial and treatment arm were missing sustained response information and were imputed using multiple imputation method. Trial 188% (N=289)86% (N=307)2.6% (-2.9%, 8.0%)70% (N=289)57% (N=307)12.7% (4.4%, 20.9%) Trial 288% (N=253)87% (N=256)1.0% (-4.8%, 6.8%)72% (N=253)57% (N=256)14.6% (5.8%, 23.
The studies that compare treatment outcomes of first recurrent C. difficile infections treated with Dificid vs extended dosing of vancomycin are Trial 1 and Trial 2 2.
- Key findings:
- DIFICID is non-inferior to vancomycin in clinical response at the end of treatment
- DIFICID is superior to vancomycin in sustained clinical response at 25 days post-treatment
- Clinical response rates:
- Trial 1: DIFICID (88%), Vancomycin (86%)
- Trial 2: DIFICID (88%), Vancomycin (87%)
- Sustained response rates:
- Trial 1: DIFICID (70%), Vancomycin (57%)
- Trial 2: DIFICID (72%), Vancomycin (57%)
From the Research
Treatment Outcomes of First Recurrent C. difficile Infections
- The treatment outcomes of first recurrent Clostridioides (C.) difficile infections treated with Dificid (fidaxomicin) vs extended dosing of vancomycin have been studied in several research papers 3, 4, 5, 6, 7.
Comparison of Fidaxomicin and Vancomycin
- A study published in 2024 compared the efficacy of fidaxomicin with oral vancomycin for the treatment of Clostridioides difficile infection in hospitalized patients receiving concomitant antibiotics for concurrent infections, and found that the rates of clinical cure and recurrent CDI were similar for fidaxomicin and vancomycin 6.
- Another study published in 2019 found that fecal microbiota transplantation was superior to fidaxomicin for treatment of recurrent Clostridium difficile infection, with a higher rate of combined clinical resolution and negative results from a polymerase chain reaction test for Clostridium difficile toxin 5.
Extended Dosing of Vancomycin
- A case report published in 2025 described the use of extended-pulsed fidaxomicin therapy for recurrent Clostridioides difficile infection after standard vancomycin and fidaxomicin failure, and found that the patient had no further recurrences for over four months 3.
- A review of treatment algorithms for Clostridium difficile infection published in 2018 suggested that vancomycin combined with fecal microbiota transplantation remains the primary therapy for multiple recurrent CDI, and that fidaxomicin is a good alternative, especially in patients at risk of relapse 4.
Limitations of Current Evidence
- A literature review published in 2013 found that the evidence to guide treatment of recurrent C. difficile infection is limited, and that there is insufficient evidence to recommend probiotics as an adjunct to conventional treatment for recurrent infection 7.