Treatment of Fulminant vs Non-Fulminant C. difficile Colitis
For fulminant C. difficile infection, use high-dose oral vancomycin 500 mg four times daily PLUS intravenous metronidazole 500 mg every 8 hours, with rectal vancomycin added if ileus is present; for non-fulminant disease, use either fidaxomicin 200 mg twice daily or vancomycin 125 mg four times daily for 10 days. 1
Defining Fulminant vs Non-Fulminant Disease
Fulminant CDI is characterized by:
- Hypotension or shock 1
- Ileus 1
- Megacolon 1
- Hemodynamic instability 1
- Signs of peritonitis (decreased bowel sounds, abdominal tenderness, rebound, guarding) 1
Non-severe CDI is defined by:
- White blood cell count ≤15,000 cells/μL 1
- Serum creatinine <1.5 mg/dL 1
- Stool frequency <4 times daily 1
Treatment Algorithm for Fulminant CDI
The critical distinction is that fulminant disease requires aggressive multi-route therapy because oral antibiotics may not reach the colon effectively due to ileus. 1
Primary Regimen:
- Vancomycin 500 mg four times daily (note the quadrupled dose compared to non-fulminant) by mouth or nasogastric tube 1
- PLUS intravenous metronidazole 500 mg every 8 hours 1
- If ileus is present, ADD rectal vancomycin instillation (500 mg in 100 mL normal saline every 4-12 hours) 1
Rationale for Combination Therapy:
The combination approach addresses the pharmacokinetic challenge that oral vancomycin may not reach the colon in patients with ileus, while IV metronidazole achieves some colonic penetration through inflamed mucosa. 1 Rectal vancomycin directly delivers high concentrations to the distal colon when oral delivery is compromised. 1
Surgical Considerations:
Colectomy should be performed urgently for:
- Colonic perforation 1
- Systemic inflammation not responding to antibiotics 1
- Toxic megacolon 1
- Severe ileus 1
- Serum lactate >5.0 mmol/L (operate before this threshold is exceeded) 1
Critical pitfall: Delaying surgery until the patient is moribund significantly worsens outcomes—surgery should be performed early in deteriorating patients. 1
Treatment Algorithm for Non-Fulminant CDI
Initial Episode (Non-Severe):
Preferred options:
Alternative if above unavailable:
- Metronidazole 500 mg three times daily for 10-14 days 1
The 2021 IDSA/SHEA guidelines represent a significant shift from older recommendations: Metronidazole is now relegated to alternative status because vancomycin demonstrates superior efficacy even in non-severe disease. 1 The 2009 ESCMID guidelines recommended metronidazole for non-severe cases 1, but this has been superseded by more recent evidence showing vancomycin's superiority. 1
First Recurrence:
Preferred:
- Fidaxomicin 200 mg twice daily for 10 days OR extended regimen (twice daily for 5 days, then every other day for 20 days) 1
Alternatives:
- Vancomycin tapered/pulsed 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
- Standard vancomycin 125 mg four times daily for 10 days (especially if metronidazole was used initially) 1
Adjunctive therapy:
- Bezlotoxumab 10 mg/kg IV once during antibiotic treatment for patients at high risk of recurrence (age >65, immunocompromised, severe CDI) 1
- Use caution in congestive heart failure 1
Second or Subsequent Recurrence:
- Same options as first recurrence 1
- Vancomycin 125 mg four times daily for 10 days PLUS rifaximin 400 mg three times daily for 20 days 1
- Fecal microbiota transplantation after at least 2 recurrences (3 total episodes) 1
Critical Management Principles
Avoid these medications:
These worsen outcomes by promoting toxin retention and increasing risk of toxic megacolon. 1
Discontinue inciting antibiotics when possible, though mild CDI induced by antibiotics may resolve with antibiotic cessation alone if closely monitored. 1
If oral therapy is impossible (severe dysphagia, complete ileus):