What is the treatment for Clostridium difficile (C. diff) colitis?

Treatment of Clostridium difficile Colitis

For initial C. difficile infection, oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days are the first-line treatments, with metronidazole relegated to situations where access to these agents is limited and only for non-severe disease. 1, 2, 3

Disease Severity Classification

Before initiating treatment, classify disease severity using objective criteria:

• Non-severe CDI: White blood cell count ≤15,000 cells/mL AND serum creatinine <1.5 mg/dL 2, 3
• Severe CDI: White blood cell count ≥15,000 cells/mL OR serum creatinine ≥1.5 mg/dL 1, 2
• Fulminant CDI: Hypotension, shock, ileus, toxic megacolon, or acute abdomen 2, 3

Additional markers of severe disease include marked left shift (>20% band neutrophils), elevated serum lactate, pseudomembranous colitis on endoscopy, colonic wall thickening on imaging, or pericolonic fat stranding 1

Initial Episode Treatment by Severity

Non-Severe Disease

First-line options (choose one):

• Oral vancomycin 125 mg four times daily for 10 days 1, 2
• Fidaxomicin 200 mg twice daily for 10 days 1, 4
• Metronidazole 500 mg three times daily for 10 days only if vancomycin and fidaxomicin are unavailable 1, 2

Fidaxomicin offers lower recurrence rates compared to vancomycin (particularly for non-027 ribotypes), making it preferable when available despite higher cost 1, 3, 5

Severe Disease

First-line options (choose one):

• Oral vancomycin 125 mg four times daily for 10 days 1, 2
• Fidaxomicin 200 mg twice daily for 10 days 1

Critical point: Vancomycin demonstrated 97% cure rate versus 76% for metronidazole in severe disease 3. Metronidazole use in severe CDI is strongly discouraged 1. Consider increasing vancomycin to 500 mg four times daily for 10 days in severe cases 1

Fulminant Disease

• High-dose oral vancomycin 500 mg four times daily 2, 3
• PLUS IV metronidazole 500 mg every 8 hours 2, 3
• If ileus present, add vancomycin 500 mg via nasogastric tube every 6 hours AND/OR vancomycin retention enema 500 mg in 100 mL normal saline every 4-12 hours 1

There is no evidence supporting fidaxomicin use in life-threatening CDI 1

Recurrent CDI Treatment

First Recurrence

Treat as initial episode unless disease has progressed from non-severe to severe 1. Fidaxomicin 200 mg twice daily for 10 days is preferred due to significantly lower rates of second recurrence (19.7% vs 35.5% with vancomycin) 3, 5

Second and Subsequent Recurrences

Preferred approach:

• Vancomycin tapered and pulsed regimen: 125 mg four times daily for 10-14 days, then 125 mg twice daily for 7 days, then 125 mg once daily for 7 days, then 125 mg every 2-3 days for 2-8 weeks 1, 3
• Alternative: Fidaxomicin 200 mg twice daily for 10 days 1

For multiple recurrences unresponsive to antibiotics: Fecal microbiota transplantation in combination with oral antibiotic treatment is strongly recommended after at least 2 recurrences 1, 3

Critical Management Principles

Immediate actions:

• Discontinue the inciting antibiotic immediately if clinically feasible 2, 3
• Avoid antiperistaltic agents and opiates as they worsen outcomes and increase complications 1, 3

Monitoring treatment response:

• Assess clinical response by 72 hours; escalate therapy if no improvement 2
• Treatment response typically requires 3-5 days 2, 3
• Do not perform "test of cure" after treatment completion 2, 3

Metronidazole safety concerns:

• Avoid repeated or prolonged courses due to cumulative and potentially irreversible neurotoxicity risk 2, 3
• If metronidazole is used and patient shows no improvement by day 3-5, escalate to vancomycin immediately rather than completing the full 10-day course 2

Surgical Intervention

Indications for total abdominal colectomy with ileostomy:

• Perforation of the colon 1
• Systemic inflammation with deteriorating clinical condition not responding to antibiotic therapy 1
• Toxic megacolon, acute abdomen, or severe ileus 1

Timing: Operate before disease becomes very severe; serum lactate >5.0 mmol/L is a marker suggesting surgery should be performed urgently 1

Special Considerations

When oral therapy is impossible (severe ileus):

• Non-severe: IV metronidazole 500 mg three times daily for 10 days 1
• Severe: IV metronidazole 500 mg three times daily PLUS vancomycin 500 mg via nasogastric tube every 6 hours AND/OR vancomycin retention enema 500 mg in 100 mL normal saline every 4-12 hours 1

Mild CDI (stool frequency <4 times daily, no signs of severe colitis) clearly induced by antibiotics may be managed by stopping the inducing antibiotic and observing closely for 48 hours, but patients must be placed on therapy immediately if deterioration occurs 1