What is the treatment for Clostridioides difficile (C. diff) infection?

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Last updated: April 29, 2025View editorial policy

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From the Guidelines

For the treatment of Clostridioides difficile infection (CDI) in adults, fidaxomicin 200 mg given twice daily for 10 days is the preferred initial treatment, as recommended by the 2021 focused update guidelines by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) 1.

Initial CDI Episode Treatment

The treatment for an initial CDI episode depends on the severity of the infection.

  • For initial episodes, fidaxomicin 200 mg twice daily for 10 days is preferred due to its effectiveness in reducing recurrence rates 1.
  • An alternative treatment is vancomycin 125 mg given four times daily by mouth for 10 days, which remains an acceptable option 1.
  • For non-severe CDI, when the preferred and alternative treatments are unavailable, metronidazole 500 mg three times daily by mouth for 10–14 days can be considered, with non-severe CDI defined by a white blood cell count of 15,000 cells/μL or lower and a serum creatinine level <1.5 mg/dL 1.

Recurrent CDI Treatment

For the first recurrence of CDI,

  • fidaxomicin 200 mg given twice daily for 10 days or a regimen of twice daily for 5 days followed by once every other day for 20 days is preferred 1.
  • Alternatively, a tapered and pulsed vancomycin regimen or vancomycin 125 mg given four times daily by mouth for 10 days can be used, especially if metronidazole was used for the initial episode 1.
  • Bezlotoxumab 10 mg/kg given intravenously once during the administration of standard of care antibiotics can be considered as an adjunctive treatment, although its use with fidaxomicin has limited data and caution is advised in patients with congestive heart failure 1.

Fulminant CDI Treatment

For fulminant CDI, characterized by hypotension, shock, ileus, or megacolon,

  • vancomycin 500 mg four times daily by mouth or by nasogastric tube is recommended, with the addition of rectal instillation of vancomycin if ileus is present 1.
  • Intravenously administered metronidazole 500 mg every 8 hours should be given together with oral or rectal vancomycin, particularly if ileus is present 1.

Additional Considerations

  • Fecal microbiota transplantation is considered for second or subsequent recurrences after appropriate antibiotic treatments have been tried 1.
  • Patients with risk factors for CDI recurrence, such as age >65 years, immunocompromised status, or severe initial CDI, may benefit from bezlotoxumab, but its implementation depends on available resources and logistics 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).

Treatment for C. difficile-associated diarrhea (CDAD): Fidaxomicin (DIFICID) is indicated for the treatment of CDAD in adult and pediatric patients aged 6 months and older.

  • The recommended dosage for adults is one 200 mg DIFICID tablet orally twice daily for 10 days.
  • For pediatric patients, the dosage is based on weight, with tablets or oral suspension administered twice daily for 10 days 2. Key points:
  • Fidaxomicin should be used only to treat infections proven or strongly suspected to be caused by C. difficile.
  • The medication should be taken exactly as directed, and the full course of therapy should be completed to decrease the effectiveness of the immediate treatment and increase the likelihood that bacteria will develop resistance 2.

From the Research

Treatment Options for C. diff Infection

  • Oral vancomycin is recommended as a first-line treatment for initial episodes of non-severe C. difficile infection 3, 4, 5.
  • Fidaxomicin is a good alternative, especially in patients at risk of relapse, and has been shown to have a lower rate of recurrence compared to vancomycin 3, 4, 5.
  • Metronidazole is no longer recommended as first-line therapy for adults due to its lower efficacy and higher risk of side effects 5.

Treatment of Recurrent C. diff Infection

  • Fecal microbiota transplantation (FMT) is a reasonable treatment option with high cure rates in patients who have had multiple recurrent episodes and have received appropriate antibiotic therapy for at least three of the episodes 6, 5, 7.
  • FMT has been shown to be superior to fidaxomicin and vancomycin in achieving clinical and microbiological resolution in patients with recurrent C. difficile infection 6.
  • Bezlotoxumab, a monoclonal antibody, has been shown to be effective in preventing recurrent C. difficile infection and is a potential treatment option for patients with recurrent disease 4, 7.

Prevention and Management

  • Good antibiotic stewardship is a key strategy to decrease rates of C. difficile infection 5, 7.
  • Discontinuation of chronic acid suppressive therapy and appropriate infection control measures, such as hand hygiene with soap and water, are also important for preventing C. difficile infection 5, 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Fidaxomicin versus vancomycin for Clostridium difficile infection.

The New England journal of medicine, 2011

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

Clostridioides difficile Infection: Update on Management.

American family physician, 2020

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.

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