From the Guidelines
The management of recurrent Clostridioides difficile infection (CDI) should prioritize fidaxomicin (standard or extended-pulsed regimen) over a standard course of vancomycin for patients with recurrent CDI episodes, as suggested by the 2021 focused update guidelines by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1.
Treatment Options
- For a first recurrence, treatment typically involves a 10-14 day course of oral vancomycin (125 mg four times daily) or fidaxomicin (200 mg twice daily) 1.
- For a second recurrence, extended vancomycin regimens are recommended, such as a standard 10-14 day course followed by a taper and pulse strategy (e.g., 125 mg twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks) 1.
- Alternatively, a 10-day course of fidaxomicin may be used 1.
- For patients with multiple recurrences, fecal microbiota transplantation (FMT) has shown high success rates (80-90%) by restoring the normal gut microbiome 1.
Adjunctive Measures
- Discontinuing unnecessary antibiotics
- Avoiding antiperistaltic agents
- Using probiotics in some cases
Underlying Mechanism
- The underlying mechanism of recurrent CDI involves disruption of the normal gut microbiome, allowing C. difficile spores to germinate and produce toxins, so treatment strategies aim to both eradicate the pathogen and restore normal gut flora 1.
Key Considerations
- Fidaxomicin is preferred over vancomycin for recurrent CDI episodes due to its lower recurrence rates and higher efficacy 1.
- FMT is a viable option for patients with multiple recurrences who have failed antibiotic treatments 1.
- The choice of treatment should be individualized based on patient factors, such as the number of recurrences, underlying medical conditions, and previous treatment responses 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. The management of recurrent CDI involves the use of bezlotoxumab (IV), specifically ZINPLAVA™, in conjunction with antibacterial drug treatment for patients at high risk of recurrence, as it is indicated to reduce recurrence of CDI 2.
- ZINPLAVA™ is not used for the treatment of CDI, but rather to reduce the risk of recurrence.
- It should only be used with antibacterial drug treatment of CDI.
From the Research
Management of Recurrent C. difficile Infection
The management of recurrent C. difficile infection involves various therapeutic approaches, including:
- Antibiotic treatment: Oral vancomycin is proposed as the first choice when antibiotic treatment for CDI is necessary 3. Fidaxomicin is a good alternative, especially in patients at risk of relapse 3, 4.
- Faecal microbiota transplantation: This therapy has demonstrated higher success rates than vancomycin, fidaxomicin, or placebo in treating recurrent C. difficile infection 5. It is considered safe, with the most common adverse reactions being abdominal discomfort and diarrhea 5.
- Standardized microbiome-based therapies: Agents such as SER-109 and RBX2660 have shown significant reduction in recurrence rates and are now US Food and Drug Administration approved for recurrent C. difficile infection 5.
- Other therapeutic strategies: Antibiotic neutralization strategies, vaccines, passive monoclonal antibodies, and drug repurposing are being explored to treat C. difficile infection 5.
Treatment Options for Specific Patient Groups
- Patients with inflammatory bowel disease: Fidaxomicin has been shown to be effective in treating C. difficile infection in these patients, with a response rate of 60.6% 6.
- Hospitalized patients receiving concomitant antibiotics: Fidaxomicin and vancomycin have similar efficacy in treating C. difficile infection in these patients, with a numerically higher proportion of patients cured with fidaxomicin 7.
Key Considerations
- Recurrence rates: The recurrence rate of C. difficile infection remains high, up to 20% after a primary infection and 60% after three or more episodes 3, 5.
- Treatment choice: The choice of therapy for recurrent C. difficile infection is different from the antibiotic used in the primary episode 5.
- Restoration of gut flora: Microbiome restoration therapies, such as faecal microbiota transplantation, aim to restore a normal gut flora and eliminate C. difficile colonization and infection 5.