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

Treatment of Clostridioides difficile Infection

First-Line Therapy for Initial 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 1, 3
• Fidaxomicin 200 mg orally twice daily for 10 days is equally effective and associated with lower recurrence rates, making it preferred when accessible 1, 4
• Metronidazole is no longer recommended for initial treatment due to inferior cure rates 1, 2

Severity Does Not Change Initial Antibiotic Choice

• Both non-severe CDI (WBC ≤15,000 cells/mL and creatinine <1.5 mg/dL) and severe CDI (WBC ≥15,000 cells/mL or creatinine >1.5 mg/dL) receive the same first-line antibiotics 1
• Higher vancomycin doses (500 mg four times daily) do not improve outcomes in severe disease 1, 5

Critical Adjunctive Measure

• Discontinue the inciting antibiotic immediately to reduce recurrence risk 1, 2

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Recurrent CDI Treatment

First Recurrence

• Vancomycin 125 mg orally four times daily for 10 days if metronidazole was used initially 1, 2
• Prolonged tapered and pulsed vancomycin regimen as an alternative 1
• Fidaxomicin 200 mg twice daily for 10 days if vancomycin was used for the initial episode 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 failed antibiotic treatments 1, 2

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NPO Patients or 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

Key Points for NPO Management

• Intravenous vancomycin alone is completely ineffective for CDI as it is not excreted into the colon 2, 3
• Vancomycin enema dosing ranges from 250-500 mg in 100-500 mL saline 2-4 times daily 2
• For severe or fulminant disease, consider higher enema doses up to 1 gram 2-4 times daily 2
• Transition to oral vancomycin or fidaxomicin once oral intake is possible 1, 2
• Trans-stoma vancomycin may be effective in surgical patients with ileostomy or colon diversion 2

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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
• Clinical improvement typically occurs within 3-5 days of starting therapy 2
• Do NOT perform a "test of cure" after treatment completion 1, 2

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Critical Pitfalls to Avoid

Medication Errors

• Never use intravenous vancomycin alone for CDI treatment—it does not reach the colon 1, 2, 3
• Avoid metronidazole for severe or recurrent CDI due to lower cure rates 1
• Do not use repeated or prolonged metronidazole courses due to cumulative neurotoxicity risk 1, 2

Management Errors

• Failing to discontinue the inciting antibiotic significantly increases recurrence risk 1, 2
• Underestimating recurrence risk—approximately 20% of patients will have recurrence, with higher rates in elderly patients 2
• Ordering unnecessary "test of cure" stool tests after treatment 1, 2

Special Monitoring Considerations

• In patients >65 years of age, monitor renal function during and after treatment as nephrotoxicity risk is increased 3
• Monitor serum vancomycin concentrations in patients with renal insufficiency, inflammatory bowel disease, or those receiving concomitant aminoglycosides, as systemic absorption can occur with oral vancomycin 3