Treatment of Clostridioides difficile Infection
First-Line Treatment for Initial CDI Episode
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 for C. difficile infection, regardless of severity. 1, 2
Treatment Selection
- Vancomycin 125 mg orally four times daily for 10 days is the standard first-line option and is FDA-approved for C. difficile-associated diarrhea 3
- Fidaxomicin 200 mg orally twice daily for 10 days is equally effective for initial cure and has lower recurrence rates, making it preferred when accessible 1, 4
- Disease severity (defined as WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL) does not change the choice between vancomycin and fidaxomicin—both are appropriate for severe and non-severe CDI 1
- Higher vancomycin doses (500 mg four times daily) provide no additional benefit for severe CDI and should not be used routinely 1, 5
Critical Action: Discontinue Inciting Antibiotics
- Stop the causative antibiotic immediately whenever possible, as this significantly reduces recurrence risk 1, 2
Important Pitfall to Avoid
- Metronidazole is no longer recommended for initial or severe CDI due to inferior cure rates compared to vancomycin 1, 2
- Intravenous vancomycin alone is completely ineffective for CDI as it is not excreted into the colon 2, 3
Treatment of Recurrent CDI
First Recurrence
- Vancomycin 125 mg orally four times daily for 10 days if metronidazole was used initially 1, 2
- Fidaxomicin 200 mg twice daily for 10 days is preferred if vancomycin was used for the initial episode, as it reduces subsequent recurrence 1
- Prolonged tapered and pulsed vancomycin regimen is an alternative approach 1
Second or Subsequent Recurrence
- Vancomycin in a tapered and pulsed regimen 1, 2
- Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1
- Fidaxomicin 200 mg twice daily for 10 days 1
- Fecal microbiota transplantation (FMT) is particularly effective after multiple recurrences and should be considered after at least 2 recurrences have failed appropriate antibiotic treatment 2, 6
Extended-Pulsed Fidaxomicin for Older Patients
- Extended-pulsed fidaxomicin (200 mg twice daily on days 1-5, then once daily on alternate days on days 7-25) achieved 70% sustained cure versus 59% with standard vancomycin in patients ≥60 years old, representing the lowest recurrence rates observed in randomized trials 7
NPO Patients or Severe Ileus
For patients unable to take oral medications, use intravenous metronidazole 500 mg every 8 hours PLUS vancomycin retention enema 500 mg in 100 mL normal saline four times daily. 1, 2
Enema Administration Details
- Vancomycin enema dosing: 250-500 mg in 100-500 mL saline administered 2-4 times daily via rectal tube 2
- For severe/fulminant CDI: Consider higher enema doses up to 1 gram 2-4 times daily 2, 8
- Transition to oral therapy (vancomycin or fidaxomicin) as soon as the patient can tolerate oral intake 2
- Trans-stoma vancomycin may be effective in surgical patients with ileostomy or colon diversion 2
Treatment Duration and Monitoring
- Standard duration is 10 days for all regimens 1, 3, 4
- Extend to 14 days if clinical response is delayed 1, 2
- Do NOT perform "test of cure" after treatment completion—this is not recommended 1, 2
- Monitor for systemic absorption in patients with inflammatory bowel disease or renal insufficiency, as clinically significant serum vancomycin levels can occur with oral administration 3
Special Monitoring for Older Patients
- Nephrotoxicity risk increases in patients >65 years old receiving oral vancomycin 3
- Monitor renal function during and after treatment in elderly patients, even those with normal baseline renal function 3
Critical Pitfalls to Avoid
- Never use metronidazole for severe or recurrent CDI—it has lower cure rates and carries neurotoxicity risk with repeated courses 1, 2
- Never rely on IV vancomycin alone—it does not reach therapeutic levels in the colon 2, 3
- Never continue the inciting antibiotic if clinically feasible to stop—this dramatically increases recurrence risk 1, 2
- Do not underestimate recurrence risk—approximately 20% of patients will experience recurrence, with higher rates in elderly patients and those requiring continued antibiotics 2, 6