From the Guidelines
For a patient with Clostridioides difficile infection (C. diff) not responding to metronidazole, the recommended approach is to switch to oral vancomycin 125 mg four times daily for 10 days, as an alternative fidaxomicin 200 mg twice daily for 10 days can be used, which may be preferred in patients at high risk for recurrence, as stated in the 2021 focused update guidelines by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1. The treatment of C. diff infection is based on the severity of the disease and the patient's response to initial treatment.
- For an initial episode of C. diff infection, the preferred treatment is fidaxomicin 200 mg twice daily for 10 days, or vancomycin 125 mg four times daily for 10 days, as recommended by the IDSA and SHEA guidelines 1.
- If the patient has not improved with metronidazole, it is essential to switch to one of the recommended treatments, such as vancomycin or fidaxomicin, to achieve a higher clinical cure rate and reduce the risk of recurrence.
- The 2021 guidelines also recommend considering the use of bezlotoxumab 10 mg/kg given intravenously once during the administration of standard of care antibiotics for patients at high risk for recurrence, such as those with a history of congestive heart failure, immunocompromised hosts, or severe C. diff infection on presentation 1. The choice of treatment should be based on the patient's individual risk factors, disease severity, and the availability of resources.
- It is crucial to discontinue the inciting antibiotic if possible, avoid antimotility agents, and implement strict contact precautions to prevent transmission.
- The treatment approach should be guided by the most recent and highest-quality evidence, such as the 2021 focused update guidelines by the IDSA and SHEA 1, which provides recommendations for the treatment of C. diff infection in adults.
From the FDA Drug Label
In two trials, Vancomycin Hydrochloride Capsules 125 mg orally four times daily for 10 days was evaluated in 266 adult subjects with C. difficile-associated diarrhea (CDAD) Enrolled subjects were 18 years of age or older and received no more than 48 hours of treatment with oral vancomycin hydrochloride or oral/intravenous metronidazole in the 5 days preceding enrollment.
The treatment for a patient with first episode of Clostridioides difficile (C. diff) infection that has not improved with metronidazole is vancomycin 125 mg orally four times daily for 10 days 2.
- Key points:
- Vancomycin dose: 125 mg orally four times daily
- Treatment duration: 10 days
- Patient population: adult subjects with C. difficile-associated diarrhea (CDAD) who received no more than 48 hours of treatment with oral vancomycin hydrochloride or oral/intravenous metronidazole in the 5 days preceding enrollment.
From the Research
Treatment Options for C. diff Infection
- For a patient with a first episode of Clostridioides difficile (C. diff) infection that has not improved with metronidazole, the treatment options include:
- Vancomycin: recommended by clinical guidelines as a first-line therapy for most cases of CDI 3
- Fidaxomicin: also recommended by clinical guidelines as a first-line therapy for most cases of CDI, and has been shown to be superior to metronidazole for a sustained clinical response and in the prevention of recurrent CDI (rCDI) in the initial episode, first recurrence, and non-severe cases 4, 3
- Fecal microbiota transplant (FMT): effective and safe for the treatment of recurrent CDI, but not typically used as a first-line treatment for initial episodes 3, 5
Comparison of Treatment Outcomes
- Studies have compared the treatment outcomes of fidaxomicin, vancomycin, and metronidazole for CDI:
- Fidaxomicin and vancomycin have been shown to have similar outcomes for sustained clinical response and prevention of rCDI in patients with multiple recurrences 4
- Fidaxomicin has been shown to be superior to metronidazole for a sustained clinical response and in the prevention of rCDI in the initial episode, first recurrence, and non-severe cases 4
- However, one study found that fidaxomicin was inferior to metronidazole for recurrent CDI (rCDI) 6
- A systematic review and meta-analysis found that fidaxomicin and vancomycin/metronidazole regimens did not have significant differences in terms of treatment outcomes, such as clinical cure, sustained cure, recurrence, and all-cause mortality 7
Clinical and Economic Outcomes
- A systematic literature review found that fidaxomicin was clinically effective compared to vancomycin, and was often reported as cost-effective, consistently within high-risk subpopulations 5
- The review also found that the higher acquisition cost of fidaxomicin was offset by reduced recurrence and hospital readmission costs 5