What are the current guidelines for Clostridioides difficile (C. diff) treatment?

From the Guidelines

The current guidelines for Clostridioides difficile (C. diff) infection treatment recommend a stratified approach based on disease severity and recurrence status, with oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days as the preferred treatment for initial non-severe episodes, 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. For initial non-severe episodes, the treatment options include:

• Oral vancomycin 125 mg four times daily for 10 days
• Fidaxomicin 200 mg twice daily for 10 days For severe infections, the same regimens are used, with the addition of intravenous metronidazole 500 mg every 8 hours for fulminant cases. Fulminant C. diff requires oral vancomycin 500 mg four times daily, often combined with intravenous metronidazole 500 mg every 8 hours, and surgical consultation for possible colectomy. For first recurrences, treatment should match the initial episode regimen, while subsequent recurrences may require extended vancomycin pulse-taper regimens or fidaxomicin. Fecal microbiota transplantation is recommended for patients with multiple recurrences who have failed appropriate antibiotic treatments, as suggested by the AGA clinical practice guideline on fecal microbiota-based therapies for select gastrointestinal diseases 1. Metronidazole (500 mg three times daily for 10 days) is now considered a second-line agent due to increasing treatment failures and should only be used for non-severe initial episodes when other agents are unavailable, as stated in the 2017 update by the IDSA and SHEA 1. These guidelines prioritize clinical cure and prevention of recurrence, as C. diff has a high recurrence rate due to persistent spores and disrupted gut microbiota. Key considerations in the treatment of C. diff infection include:
• Disease severity and recurrence status
• Treatment options, including vancomycin, fidaxomicin, and metronidazole
• Fecal microbiota transplantation for patients with multiple recurrences
• Prevention of recurrence and clinical cure.

From the FDA Drug Label

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 recommended dosage for adults is one 200 mg DIFICID tablet orally twice daily for 10 days. The recommended dosage for pediatric patients weighing at least 12.5 kg and able to swallow tablets is one 200 mg DIFICID tablet administered orally twice daily for 10 days.

The current guidelines for C. difficile treatment with fidaxomicin are to use it only for infections proven or strongly suspected to be caused by C. difficile. The recommended dosage is:

• Adults: 200 mg orally twice daily for 10 days
• Pediatric patients (6 months to less than 18 years of age):
  • Weighing at least 12.5 kg and able to swallow tablets: 200 mg orally twice daily for 10 days
  • Unable to swallow tablets: dosed with DIFICID oral suspension based on weight, as shown in Table 1, administered orally twice daily for 10 days 2

From the Research

Current Guidelines for CDI Treatment

• The cornerstones for the treatment of CDI are vancomycin and fidaxomicin 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.
• In recurrent CDI, 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.
• Faecal microbiota transplantation (FMT) should be offered to patients with frequently recurring CDI 3, 4, 5.

Treatment Options

• Orally administered vancomycin and fidaxomicin are the therapeutic options of choice for initial C. difficile infection 4, 5.
• Fidaxomicin is recommended as first-line therapy for all patients with Clostridioides difficile infection (CDI) 6.
• Fecal microbiota transplant is performed in gastroenterological centers that have experience with this form of treatment after multiple failures of drug treatment for recurrent infection 4.
• Novel antibiotics with narrow-spectrum activity and low intestinal resorption, including surotomycin, cadazolid, and ridinilazol, are being developed 5.
• Novel toxoid vaccines are expected to be efficacious in the prevention of C. difficile infection 5.

Special Considerations

• Critically ill patients require treatment administered by an interdisciplinary team and consists of early surgical intervention in combination with drug treatment 4.
• Concomitant antibiotic use during the initial CDI episode is a major risk factor for recurrent CDI, and the comparative efficacy of fidaxomicin versus vancomycin in this setting is being studied 7.