What is the recommended outpatient treatment for Clostridioides (C.) difficile?

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Last updated: October 23, 2025View editorial policy

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Outpatient Treatment for Clostridioides difficile Infection

For initial episodes of C. difficile infection (CDI), oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the recommended first-line treatments. 1, 2, 3

Disease Severity Assessment

  • Non-severe CDI is characterized by stool frequency <4 times daily, no signs of severe colitis, and white blood cell count <15 × 10^9/L 2, 3
  • Severe CDI is characterized by one or more of: fever, hemodynamic instability, leukocytosis (white blood cell count ≥15 × 10^9/L), serum creatinine ≥1.5 mg/dL, or pseudomembranous colitis on endoscopy 1, 3

Initial Treatment Recommendations

Non-Severe CDI

  • First-line treatment: Oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days 1, 2
  • Alternative treatment (if access to vancomycin or fidaxomicin is limited): Oral metronidazole 500 mg three times daily for 10 days 2, 3

Severe CDI

  • First-line treatment: Oral vancomycin 125 mg four times daily for 10 days 1, 2, 3
  • Fidaxomicin 200 mg twice daily for 10 days is also effective for severe cases 4

Treatment of Recurrent CDI

First Recurrence

  • Recommended treatment: Oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days 1, 2
  • Fidaxomicin may be preferred due to lower rates of secondary recurrences compared to vancomycin 5, 6

Second or Subsequent Recurrences

  • Treatment options include:
    • Oral vancomycin with a tapered and pulsed regimen (e.g., 125 mg four times daily for 10-14 days, then twice daily for 7 days, then once daily for 7 days, then every 2-3 days for 2-8 weeks) 5, 3
    • Oral vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 5
    • Fidaxomicin 200 mg twice daily for 10 days 5, 3
    • Fecal microbiota transplantation (FMT) after completion of a standard course of antibiotics 5

Fecal Microbiota Transplantation (FMT)

  • FMT is strongly recommended for multiple recurrent CDI unresponsive to repeated antibiotic treatment 5, 3
  • FMT should be offered to patients who have had at least two recurrences, or those who have had one recurrence and have risk factors for further episodes 5
  • FMT should be given upon completion of a course of standard antibiotics for recurrent CDI 5
  • Antibiotics for CDI should ideally be stopped 1-3 days before conventional FMT 5
  • Prevention of CDI recurrence following FMT ranges from 70% to 90% 5

Special Considerations

  • Discontinue the inciting antibiotic if possible to reduce risk of recurrence 1, 2
  • Avoid antiperistaltic agents and opiates in patients with CDI 2, 3
  • For pediatric patients older than 12 months, oral vancomycin can be used at a dose of 10 mg/kg/dose four times daily (maximum 125 mg per dose) 1
  • For pediatric patients 6 months to less than 18 years of age, fidaxomicin is FDA-approved with weight-based dosing 4
  • In mildly or moderately immunocompromised adults with recurrent CDI, conventional FMT is suggested 5
  • In severely immunocompromised adults with recurrent CDI, fecal microbiota-based therapies are not recommended 5

Monitoring and Follow-up

  • Clinical response should be the primary measure of treatment success rather than repeat stool testing 5, 7
  • In patients with IBD and CDI, symptoms may overlap, making assessment of treatment response challenging 5
  • Patients >65 years of age should have renal function monitored during and following treatment with oral vancomycin to detect potential nephrotoxicity 8

Prevention Strategies

  • Good antibiotic stewardship is a key strategy to decrease rates of CDI 7
  • Hand hygiene with soap and water is superior to alcohol-based products during outbreaks 7

References

Guideline

Treatment of Outpatient Clostridioides difficile Infection

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Empiric Antibiotic Treatment for Infectious Colitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Antibiotic Treatment for Clostridium difficile Colitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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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