What is the recommended antibiotic regimen for Clostridioides difficile (C. diff) infection?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Article Review Status
Submitted
Under Review
Approved

Last updated: March 9, 2025 • View editorial policy

From the Guidelines

For Clostridioides difficile (C. diff) infection, the recommended antibiotic regimen is fidaxomicin 200 mg given twice daily for 10 days as the preferred treatment for initial episodes, with vancomycin 125 mg given 4 times daily for 10 days as an acceptable alternative, 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.

Key Considerations

  • The choice of antibiotic regimen depends on the severity of the infection and whether it's a first occurrence or recurrence.
  • For initial episodes, fidaxomicin and vancomycin are the preferred treatments, with metronidazole considered for non-severe cases when other options are unavailable.
  • For recurrent cases, options include vancomycin in a tapered and pulsed regimen, fidaxomicin extended regimen, or consideration of fecal microbiota transplantation.

Treatment Regimens

  • Initial episode, non-severe: fidaxomicin 200 mg twice daily for 10 days or vancomycin 125 mg 4 times daily for 10 days.
  • Initial episode, severe: vancomycin 125 mg 4 times daily for 10 days.
  • Initial episode, fulminant: vancomycin 500 mg 4 times daily by mouth or by nasogastric tube, with intravenous metronidazole 500 mg every 8 hours added if ileus is present.
  • First recurrence: fidaxomicin 200 mg twice daily for 10 days or vancomycin in a tapered and pulsed regimen.
  • Second or subsequent recurrence: vancomycin in a tapered and pulsed regimen, vancomycin followed by rifaximin, fidaxomicin, or fecal microbiota transplantation.

Rationale

The recommended regimens are based on the most recent guidelines from the IDSA and SHEA, which prioritize fidaxomicin and vancomycin as the primary treatments for C. diff infection due to their efficacy and safety profiles, as well as their ability to reduce recurrence rates 1. Metronidazole is considered a second-line agent due to increasing resistance and is only recommended for mild cases when other options are not available. The guidelines also emphasize the importance of considering the severity of the infection and the patient's risk factors for recurrence when selecting a treatment regimen.

From the FDA Drug Label

Vancomycin Hydrochloride Capsules are indicated for the treatment of C. difficile-associated diarrhea. The recommended dose is 125 mg administered orally 4 times daily for 10 days. DIFICID is a macrolide antibacterial indicated in adult and pediatric patients 6 months of age and older for the treatment of C. difficile-associated diarrhea. Adults: One 200 mg tablet orally twice daily for 10 days.

The recommended antibiotic regimens for C. diff infection are:

  • Vancomycin: 125 mg orally 4 times daily for 10 days 2
  • Fidaxomicin: 200 mg orally twice daily for 10 days 3

From the Research

The recommended antibiotic regimen for Clostridioides difficile (C. diff) infection varies depending on the severity of the disease and the patient's medical history.

  • For non-severe and severe disease, fidaxomicin is now promoted to first-line therapy, along with vancomycin, due to its increased efficacy in preventing recurrence 4, 5, 6.
  • Metronidazole is not preferred for the treatment of C. diff infection, except in cases of severe-complicated infection, where it may be used in combination with high-dose oral and rectal vancomycin 4.
  • Bezlotoxumab is endorsed for the prevention of recurrent infection 4, 6, 7.
  • Faecal microbiota transplantation (FMT) is recommended for the treatment of multiple recurrent C. diff infections, particularly in cases where antibiotic treatment has failed 4, 5, 8, 7.

Severe-Complicated C. diff Infection

For severe-complicated C. diff infection, the IDSA/SHEA recommends high-dose oral and rectal vancomycin, along with IV metronidazole 4.

  • The ESCMID has endorsed fidaxomicin and tigecycline as part of combination anti-C. diff therapy for severe-complicated infection 4.
  • FMT may also be considered as a treatment option for severe-complicated refractory disease, although further study is needed to determine the optimal timing and mode of FMT in these cases 4, 8.

Emerging Therapies

Several emerging therapies are being developed for the treatment of C. diff infection, including:

  • New antibiotics, such as teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571 5, 6.
  • Preventive medications against recurrence, such as Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2 6.
  • Primary prevention strategies, such as vaccines, ribaxamase, and DAV132 6.
  • Alternative binding proteins and immunomodulation therapies, such as monoclonal antibodies and small-molecule agents 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.