What is the treatment for the first episode of Clostridioides difficile (C. difficile) infection?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 24, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

For the first episode of Clostridioides difficile infection (CDI), fidaxomicin 200 mg given twice daily for 10 days is the preferred treatment, as it has been associated with lower recurrence rates compared to vancomycin, according to the 2021 clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) 1.

Key Points to Consider

  • Fidaxomicin is a narrow-spectrum macrocyclic antibiotic that is FDA-approved for the initial treatment of C. difficile infections.
  • Oral vancomycin (125 mg four times daily for 10 days) is also a first-line option, particularly for severe cases, but fidaxomicin is preferred due to its lower recurrence rates.
  • The 2021 guideline suggests using fidaxomicin rather than a standard course of vancomycin for patients with an initial CDI episode, with a conditional recommendation and moderate certainty of evidence 1.
  • The choice of treatment depends on the severity of the disease, with vancomycin being an acceptable alternative for severe cases.

Treatment Options

  • Fidaxomicin 200 mg given twice daily for 10 days
  • Vancomycin 125 mg given 4 times daily for 10 days
  • Metronidazole 500 mg 3 times daily for 10-14 days (for non-severe CDI, if fidaxomicin and vancomycin are unavailable)

Important Considerations

  • IV vancomycin is not effective for C. difficile infections because it does not achieve adequate concentrations in the gut.
  • Fidaxomicin has the advantage of causing less disruption to the normal gut microbiota.
  • The 2021 guideline provides recommendations for the treatment of CDI, including the use of fidaxomicin, vancomycin, and metronidazole, as well as adjunctive treatments such as bezlotoxumab 1.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Clostridioides difficile-Associated Diarrhea DIFICID® is indicated in adult and pediatric patients aged 6 months and older for the treatment of C. difficile-associated diarrhea (CDAD).

1 INDICATIONS AND USAGE

Vancomycin Hydrochloride Capsules are indicated in pediatric patients less than 18 years of age for the treatment of C. difficile associated diarrhea

The treatment for the first episode of Clostridioides difficile (C. difficile) infection is:

  • Fidaxomycin (PO), as indicated in the drug label 2
  • Vancomycin (PO), as indicated in the drug label 3

From the Research

Treatment Options for First Episode of C. difficile Infection

  • The primary treatment options for the first episode of Clostridioides difficile (C. difficile) infection are fidaxomicin and vancomycin 4, 5, 6, 7, 8.
  • Fidaxomicin and vancomycin have been compared in several studies, with fidaxomicin showing a lower rate of recurrence in some cases 4, 5, 6, 7.

Efficacy of Fidaxomicin and Vancomycin

  • A phase 3 clinical trial found that fidaxomicin was noninferior to vancomycin in achieving clinical cure, with a lower rate of recurrence 4.
  • Another study found that fidaxomicin was similar to vancomycin in achieving a clinical response at the end of therapy, but superior in preventing a second recurrence within 28 days 5.
  • A systematic review and meta-analysis found that fidaxomicin was associated with a 31% reduction in the risk of recurrence compared to vancomycin 7.

Use of Concomitant Antibiotics

  • The use of concomitant antibiotics during treatment for C. difficile infection can compromise the initial response to therapy and durability of response 6, 8.
  • Fidaxomicin has been shown to be more effective than vancomycin in achieving clinical cure in the presence of concomitant antibiotic therapy 6.
  • A randomized, controlled trial found that fidaxomicin and vancomycin had similar rates of clinical cure and recurrence in patients receiving concomitant antibiotics, although the study had a small sample size and low recurrence rate 8.

Comparison of Fidaxomicin and Vancomycin

  • Fidaxomicin and vancomycin have been compared in various studies, with fidaxomicin showing a lower rate of recurrence in some cases 4, 5, 6, 7.
  • The choice between fidaxomicin and vancomycin may depend on various factors, including the presence of concomitant antibiotics and the severity of the infection 6, 7, 8.

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.