What is the treatment for recurrent Clostridioides difficile (C. diff) infection?

From the Guidelines

The treatment of recurrent Clostridioides difficile (C. diff) infection should prioritize fecal microbiota transplantation (FMT) for patients with multiple recurrences, as it has shown high success rates (80-90%) by restoring normal gut microbiota 1. For a first recurrence, oral vancomycin 125 mg four times daily for 10-14 days or fidaxomicin 200 mg twice daily for 10 days is recommended, as outlined in the 2021 focused update guidelines by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1. Some key points to consider when treating recurrent C. diff infection include:

• For a second recurrence, a tapered and pulsed regimen of vancomycin is preferred: 125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, followed by every 2-3 days for 2-8 weeks, as an alternative to fidaxomicin 200 mg twice daily for 10 days 1.
• Bezlotoxumab, a monoclonal antibody against C. diff toxin B, may be added to standard antibiotic therapy to prevent recurrence in high-risk patients, with caution in patients with congestive heart failure 1.
• Throughout treatment, patients should avoid unnecessary antibiotics, proton pump inhibitors, and maintain good hand hygiene to minimize the risk of recurrence and promote a healthy gut microbiome.
• Fecal microbiota transplantation (FMT) is recommended for patients with multiple recurrences of C. diff infection who have failed appropriate antibiotic treatments, with careful consideration of the patient's immunocompromised status and potential need for alternative therapies 1.

From the FDA Drug Label

ZINPLAVA is indicated to reduce recurrence of Clostridioides difficile infection (CDI) in adults and pediatric patients 1 year of age and older who are receiving antibacterial drug treatment for CDI and are at a high risk for CDI recurrence. Limitation of Use: ZINPLAVA is not indicated for the treatment of CDI. ZINPLAVA is not an antibacterial drug. ZINPLAVA should only be used in conjunction with antibacterial drug treatment of CDI.

The treatment of recurrent C. diff is not directly addressed by the use of bezlotoxumab (IV), as it is indicated to reduce recurrence of CDI, not to treat it.

• Bezlotoxumab (IV) is used in conjunction with antibacterial drug treatment of CDI.
• The FDA drug label does not provide information on the treatment of recurrent C. diff using bezlotoxumab (IV) as a standalone treatment 2, 2, 2.

From the Research

Treatment Options for Recurrent C. difficile Infection

• Fidaxomicin is a suggested treatment for initial and recurrent C. difficile infection, as stated in the study 3.
• Oral vancomycin is an acceptable alternative, followed by rifaximin and fecal microbiota transplantation, according to the study 3.
• Bezlotoxumab is suggested in recurrent cases within 6 months, as mentioned in the study 3.
• Extended-pulsed fidaxomicin (EPFX) has been proposed to reduce recurrence, especially in high-risk patients, as seen in the case report 4.
• Fecal microbiota transplantation remains available in limited settings for recurrent C. difficile infection, as noted in the study 5.

Patient Considerations

• Patients with multiple high-risk features, including advanced age, active malignancy, and prior treatment failures, may benefit from extended-pulsed fidaxomicin, as shown in the case report 4.
• Patients with inflammatory bowel disease may respond to treatment with fidaxomicin, with a response rate of 60.6% in one study 6.
• Patients who fail to respond to fidaxomicin may undergo fecal microbiota transplantation, which was effective in 76.9% of patients in one study 6.

Treatment Outcomes

• Fidaxomicin led to resolution of C. difficile infection in 60.6% of patients with inflammatory bowel disease, with a median time to recurrence of 55 days, as reported in the study 6.
• In a randomized trial, fidaxomicin and vancomycin had similar rates of clinical cure and recurrent C. difficile infection in hospitalized patients receiving concomitant antibiotics, as seen in the study 7.
• The use of extended-pulsed fidaxomicin resulted in no further recurrences for over four months in a patient with multiple prior relapses, as described in the case report 4.