What is the recommended treatment for Clostridium (C. difficile) infection?

Treatment of Clostridioides difficile Infection

First-Line Treatment for Initial Episodes

For any initial episode of C. difficile infection, use oral vancomycin 125 mg four times daily for 10 days OR fidaxomicin 200 mg twice daily for 10 days, regardless of disease severity. 1

Treatment Selection Algorithm

• Vancomycin 125 mg orally four times daily for 10 days is the standard first-line option with strong evidence 1, 2
• Fidaxomicin 200 mg orally twice daily for 10 days is equally effective for initial treatment and associated with significantly lower recurrence rates (15% vs 25-31% with vancomycin) 3, 4, 5
• Metronidazole should be avoided for initial episodes; it is only acceptable in resource-limited settings where vancomycin or fidaxomicin are unavailable, and only for non-severe disease 1

The traditional severity classification (WBC ≥15,000 cells/mL or serum creatinine >1.5 mg/dL) no longer changes initial antibiotic selection, as both vancomycin and fidaxomicin are recommended regardless of severity 1, 3. Higher doses of vancomycin (500 mg four times daily) provide no additional benefit for severe disease 3, 6, 7.

Fulminant C. difficile Infection

For fulminant CDI (hypotension/shock, ileus, or megacolon), use vancomycin 500 mg orally or via nasogastric tube four times daily PLUS intravenous metronidazole 500 mg every 8 hours. 1, 4

Fulminant Disease Management

• Add vancomycin retention enema 500 mg in 100 mL normal saline every 6 hours if ileus is present 1, 4
• Intravenous vancomycin alone is completely ineffective for CDI and should never be used 3, 4
• This is the only scenario where metronidazole has a role in modern CDI treatment 1

First Recurrence Treatment

For first recurrence, use fidaxomicin 200 mg twice daily for 10 days as the preferred option. 3, 4

Alternative Regimens for First Recurrence

• Prolonged tapered and pulsed vancomycin regimen: 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 1, 3
• Standard vancomycin 125 mg four times daily for 10 days if metronidazole was used for the initial episode 1, 3
• Never use metronidazole for recurrent disease due to lower cure rates and cumulative neurotoxicity risk 3, 4

Multiple Recurrences (≥2 Recurrences)

For second or subsequent recurrences, fecal microbiota transplantation (FMT) is the most effective option after at least 2 failed antibiotic courses. 1, 4

Treatment Options for Multiple Recurrences

• Vancomycin tapered and pulsed regimen as described above 1, 3
• Vancomycin 125 mg four times daily for 10 days followed by rifaximin 400 mg three times daily for 20 days 1, 3
• Fidaxomicin 200 mg twice daily for 10 days 1, 3
• FMT has strong evidence (moderate quality) and should be offered after appropriate antibiotic trials 1, 4

Special Populations and Situations

Pediatric Patients (≥6 months to <18 years)

• Vancomycin 10 mg/kg/dose orally four times daily (maximum 125 mg per dose) for 10 days 4, 2
• Fidaxomicin weight-based dosing for patients ≥6 months old 4, 5
• Either vancomycin or fidaxomicin is recommended for initial episodes and first recurrence 1

NPO Patients or Ileus

• Intravenous metronidazole 500 mg every 8 hours PLUS vancomycin retention enema 500 mg in 100 mL normal saline four times daily 3, 4
• Transition to oral vancomycin or fidaxomicin once oral intake is possible 3, 4

Critical Management Principles

Essential Actions

• Discontinue the inciting antibiotic immediately as this is the single most important factor in reducing recurrence risk 1, 3, 4
• Start empiric therapy when substantial laboratory confirmation delay is expected or for fulminant disease 1
• Standard treatment duration is 10 days, with consideration for extending to 14 days if response is delayed 1, 3
• Clinical response is expected within 3-5 days after starting therapy 4

Monitoring Considerations

• In patients >65 years old, monitor renal function during and after treatment due to increased nephrotoxicity risk 2
• Monitor serum vancomycin concentrations in patients with renal insufficiency, inflammatory bowel disease, or those receiving concomitant aminoglycosides, as systemic absorption can occur 2

Critical Pitfalls to Avoid

• Never use intravenous vancomycin alone for CDI—it is not excreted into the colon and is completely ineffective 3, 4, 2
• Avoid metronidazole for severe or recurrent CDI due to inferior cure rates compared to vancomycin 3, 4
• Do not use antiperistaltic agents or opiates in patients with active CDI 4
• Never perform a "test of cure" after treatment completion—this is not recommended 3, 4
• Avoid repeated or prolonged metronidazole courses due to cumulative and potentially irreversible neurotoxicity 1, 3
• Do not fail to discontinue the inciting antibiotic—this dramatically increases recurrence risk 3, 4
• Higher vancomycin doses (>500 mg/day) provide no benefit for non-fulminant disease and increase cost without improving outcomes 3, 6, 7