What are the next steps for a patient with persistent diarrhea symptoms despite a course of vancomycin for Clostridioides difficile (C. diff) infection?

From the Guidelines

For a patient with persistent diarrhea despite vancomycin treatment for C. difficile infection, the next steps should include retesting stool for C. difficile toxin to confirm whether this represents treatment failure or recurrence. If C. difficile is confirmed, fidaxomicin 200 mg twice daily for 10 days is recommended as the first-line treatment due to its lower recurrence rates compared to vancomycin 1. Alternatively, extended vancomycin therapy with a tapered and pulsed regimen can be considered, typically starting with 125 mg four times daily for 10-14 days, followed by gradual tapering over several weeks 1. For multiple recurrences, bezlotoxumab (a monoclonal antibody) can be added as adjunctive therapy, or fecal microbiota transplantation may be considered 1. Key considerations in the management of recurrent C. difficile infection include:

• Retesting stool for C. difficile toxin to confirm recurrence
• Using fidaxomicin as the first-line treatment for recurrent C. difficile infection
• Considering alternative treatments such as vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab for patients who are not interested in fecal microbiota-based therapies
• Fecal microbiota transplantation as an option for patients with multiple recurrences or severe disease If C. difficile testing is negative, other causes of persistent diarrhea should be investigated, including post-infectious irritable bowel syndrome, inflammatory bowel disease, or other enteric infections. During treatment, patients should maintain good hydration, avoid antimotility agents, and continue probiotics which may help restore normal gut flora. These approaches address the disrupted gut microbiome that allows C. difficile to flourish and aim to prevent further recurrences by promoting restoration of healthy intestinal bacteria. The use of fecal microbiota-based therapies, including conventional FMT, fecal microbiota live-jslm, and fecal microbiota spores live-brpk, can be considered in select patients with recurrent C. difficile infection, particularly those who have failed standard antibiotic treatments or have significant comorbidities 1. However, the decision to use these therapies should be made on a case-by-case basis, taking into account the individual patient's risk factors, medical history, and potential benefits and risks of treatment.

From the FDA Drug Label

1.1 Clostridioides difficile-Associated Diarrhea DIFICID® is indicated in adult and pediatric patients aged 6 months and older for the treatment of C. difficile-associated diarrhea (CDAD).

The next steps for a patient with persistent diarrhea symptoms despite a course of vancomycin for Clostridioides difficile (C. diff) infection could be to consider treatment with fidaxomicin (DIFICID), as it is indicated for the treatment of C. difficile-associated diarrhea (CDAD) in adults and pediatric patients aged 6 months and older.

• The recommended dosage for adults is one 200 mg DIFICID tablet orally twice daily for 10 days.
• For pediatric patients, the dosage is based on weight, as shown in Table 1 of the drug label. The patient should be closely monitored for any signs of improvement or worsening of symptoms, and the treatment plan should be adjusted accordingly 2.

From the Research

Next Steps for Persistent Diarrhea Symptoms

Despite a course of vancomycin for Clostridioides difficile (C. diff) infection, the following steps can be considered:

• Re-evaluation of the patient's condition to determine the cause of persistent diarrhea symptoms 3, 4
• Consideration of alternative treatments for C. diff infection, such as:
  • Fecal bacteriotherapy 3, 5
  • Rifaximin chaser 3
  • Nitazoxanide 3
  • Probiotics 3
  • Intravenous immunoglobulin 3
  • Fidaxomicin 3, 6
• Assessment of the patient's response to the initial vancomycin treatment and consideration of a longer duration of vancomycin therapy, as studies have shown that long-duration oral vancomycin can be effective in reducing recurrence rates 6
• Evaluation for other potential causes of persistent diarrhea, such as other infectious agents or underlying conditions 4

Considerations for Treatment

• The choice of treatment should be based on the severity of the patient's symptoms, the presence of any underlying conditions, and the results of diagnostic testing 3, 4
• Treatment options should be guided by clinical guidelines and expert opinion, as the evidence base for some treatments may be limited 3
• Close monitoring of the patient's response to treatment and adjustment of the treatment plan as needed 7, 6

Diagnostic Considerations

• Diagnostic testing, such as stool tests and imaging studies, may be necessary to determine the cause of persistent diarrhea symptoms 7, 4
• Consideration of the patient's medical history, including any previous episodes of C. diff infection or other gastrointestinal conditions 3, 6