What is the treatment algorithm for Clostridioides difficile (C. diff) 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: May 12, 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

The treatment algorithm for Clostridioides difficile (C. diff) infection should prioritize fidaxomicin 200 mg twice daily for 10 days as the first-line therapy for initial mild to moderate cases, as recommended by the most recent guidelines 1. The choice of treatment depends on the severity and recurrence status of the infection.

  • For initial mild to moderate cases, fidaxomicin 200 mg twice daily for 10 days is the preferred treatment, with vancomycin 125 mg four times daily for 10 days as an alternative 1.
  • For severe or fulminant infections, vancomycin 500 mg four times daily by mouth or by nasogastric tube, plus intravenous metronidazole 500 mg every 8 hours, is recommended, with consideration for vancomycin enemas if ileus is present 1.
  • For first recurrence, fidaxomicin 200 mg twice daily for 10 days or a vancomycin taper and pulse regimen is recommended, with bezlotoxumab as an adjunctive treatment for patients at high risk of recurrence 1.
  • For multiple recurrences, fidaxomicin or fecal microbiota transplantation should be considered after a course of vancomycin 1. Supportive care includes fluid resuscitation, avoiding antimotility agents, and discontinuing the inciting antibiotic if possible, as recommended by previous guidelines 1. The most recent guidelines 1 provide the best evidence for the treatment of C. diff infection, and should be prioritized in clinical practice.

From the FDA Drug Label

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. 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 treatment algorithm for C. difficile is to use DIFICID (fidaxomicin) for the treatment of C. difficile-associated diarrhea in adult and pediatric patients 6 months of age and older. The dosage is:

  • Adults: One 200 mg tablet orally twice daily for 10 days.
  • Pediatrics (6 Months to Less than 18 Years of Age):
    • Pediatric patients weighing at least 12.5 kg and able to swallow tablets: One 200 mg tablet orally twice daily for 10 days.
    • Pediatric patients weighing at least 4 kg: Weight-based dosing of the oral suspension twice daily for 10 days using an oral dosing syringe, as specified in Table 1 in the full prescribing information 2.

From the Research

Treatment Algorithm for C. difficile

The treatment algorithm for C. difficile infection (CDI) involves various therapeutic approaches, including antibiotics, fecal microbiota transplantation, and novel therapies.

  • The first-line treatment for CDI is oral vancomycin or fidaxomicin, as recommended by the 2017 Infectious Diseases Society of America (IDSA) guidelines 3.
  • Metronidazole is no longer considered a first-line treatment due to its lower efficacy and higher recurrence rate compared to vancomycin and fidaxomicin 4, 5.
  • Fidaxomicin is a good alternative to vancomycin, especially in patients at risk of relapse, and has been shown to be superior to metronidazole and vancomycin in preventing recurrent CDI 5.
  • For multiple recurrent CDI, vancomycin combined with fecal microbiota transplantation is the primary therapy 4, 6.
  • Novel therapies, such as surotomycin, cadazolid, and ridinilazole, are being developed and have shown promise in phase 1 and 2 trials 3, 7.
  • Monoclonal antibodies and vaccines are also being investigated as potential therapeutic options for CDI 4, 7.

Treatment Options

The following treatment options are available for CDI:

  • Oral vancomycin: first-line treatment for initial episode and first recurrence 4, 3
  • Fidaxomicin: alternative to vancomycin, especially in patients at risk of relapse 5
  • Metronidazole: no longer considered a first-line treatment due to lower efficacy and higher recurrence rate 4, 5
  • Fecal microbiota transplantation: primary therapy for multiple recurrent CDI 4, 6
  • Novel therapies: surotomycin, cadazolid, and ridinilazole, currently in phase 1 and 2 trials 3, 7

Special Considerations

  • Severe CDI: requires early surgical intervention in combination with drug treatment 6
  • Critically ill patients: requires treatment by an interdisciplinary team and consists of early surgical intervention in combination with drug treatment 6
  • Recurrent CDI: requires specifically adapted treatment modalities, including fecal microbiota transplantation 4, 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Navigating changes in Clostridioides difficile prevention and treatment.

Journal of managed care & specialty pharmacy, 2020

Research

Update of treatment algorithms for Clostridium difficile infection.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2018

Research

Fidaxomicin versus metronidazole, vancomycin and their combination for initial episode, first recurrence and severe Clostridioides difficile infection - An observational cohort study.

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, 2021

Research

Emerging drugs for the treatment of clostridium difficile.

Expert opinion on emerging drugs, 2019

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.