From the Guidelines
The current management approach for Clostridioides difficile infection (CDI) involves a stratified treatment strategy based on disease severity and recurrence status, with fidaxomicin (200 mg twice daily for 10 days) being the preferred treatment for initial non-severe CDI, as recommended by the 2021 focused update guidelines by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1. For initial non-severe CDI, oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) is recommended as first-line therapy.
- Key considerations for treatment include:
- Disease severity: severe or fulminant CDI requires oral vancomycin (125-500 mg four times daily) with the addition of intravenous metronidazole (500 mg every 8 hours) in fulminant cases.
- Recurrence status: recurrent CDI may be treated with extended vancomycin regimens (tapered and pulsed), fidaxomicin, or fecal microbiota transplantation (FMT).
- Supportive care includes:
- Fluid and electrolyte replacement
- Avoiding antimotility agents
- Discontinuing the inciting antibiotic if possible
- Prevention strategies focus on:
- Antimicrobial stewardship
- Contact precautions
- Environmental cleaning to reduce transmission The pathophysiology of CDI involves disruption of normal gut flora by antibiotics, allowing C. difficile to proliferate and produce toxins that cause colonic inflammation and damage, as described in the 2017 update by the IDSA and SHEA 1. FMT has shown high success rates (80-90%) for multiple recurrences by restoring gut microbiota diversity, and is recommended for patients with multiple recurrences of CDI who have failed appropriate antibiotic treatments, as suggested by the AGA clinical practice guideline on fecal microbiota-based therapies for select gastrointestinal diseases 1. Overall, the management of CDI requires a comprehensive approach that takes into account the severity and recurrence of the infection, as well as the need for supportive care and prevention strategies to reduce transmission and improve patient outcomes.
From the FDA Drug Label
DIFICID® is indicated in adult and pediatric patients aged 6 months and older for the treatment of C. difficile-associated diarrhea (CDAD). To reduce the development of drug-resistant bacteria and maintain the effectiveness of DIFICID and other antibacterial drugs, DIFICID should be used only to treat infections that are proven or strongly suspected to be caused by C. difficile. The current management approach for Clostridioides (C.) difficile infection involves the use of fidaxomicin (PO), which is indicated for the treatment of C. difficile-associated diarrhea (CDAD) in adult and pediatric patients aged 6 months and older. The recommended dosage for adults is one 200 mg tablet orally twice daily for 10 days, while pediatric patients may receive weight-based dosing of the oral suspension twice daily for 10 days 2. It is essential to use fidaxomicin only to treat infections proven or strongly suspected to be caused by C. difficile to reduce the development of drug-resistant bacteria 2.
- Key considerations:
- Use fidaxomicin only for the treatment of C. difficile-associated diarrhea
- Administer fidaxomicin orally with or without food
- Follow the recommended dosage and administration instructions
- Monitor for adverse reactions, such as nausea, vomiting, and abdominal pain 2
From the Research
Current Management Approach for Clostridioides (C.) difficile Infection
The current management approach for Clostridioides (C.) difficile infection involves several treatment options, including:
- Vancomycin and fidaxomicin as the cornerstones for the treatment of CDI 3
- Metronidazole should be used only in mild-to-moderate disease in younger patients who have no or only few risk factors for recurrence 3
- Bezlotoxumab infusion (a monoclonal antibody against C. difficile toxin B) may be considered as an adjunctive therapeutic strategy in addition to the standard care provided to patients with several risk factors for recurrence 3, 4, 5, 6
- Faecal microbiota transplantation (FMT) should be offered to patients with frequently recurring CDI 3, 4, 5, 6
Treatment Options
The treatment options for CDI have undergone major changes, with current recommendations speaking against using metronidazole for primary CDI 3. Fidaxomicin and bezlotoxumab have been added to the treatment armamentarium, and microbial replacement therapies have emerged 3, 4, 5, 6. Several other therapies are undergoing clinical trials 3, 4, 5, 6.
Prevention and Future Perspectives
Antibiotic stewardship and infection control measures will remain essential components for CDI management 5, 6. Future advancements in microbiota targeting treatments will emerge as promising alternatives to standard CDI treatments 5, 6. Validated risk prediction tools are needed to identify patients most likely to benefit from these treatments 5.
Comparison of Treatment Regimens
Fidaxomicin was found to be superior to metronidazole, vancomycin, or their combination for a sustained clinical response and in the prevention of recurrent CDI in the overall population 7. In subgroup analyses, fidaxomicin was superior to vancomycin or metronidazole for a sustained clinical response and in the prevention of recurrent CDI in the initial episode, first recurrence, and non-severe cases 7.