Treatment of Severe Clostridioides difficile Infection
For severe C. difficile infection, oral vancomycin 125 mg four times daily for 10 days is the recommended first-line treatment, with fidaxomicin 200 mg twice daily for 10 days as an alternative option. 1
Defining Severe CDI
Before initiating treatment, confirm the patient meets criteria for severe disease:
- Leukocytosis with WBC >15 × 10^9/L 1
- Serum albumin <30 g/L (or <3 g/dL) 1
- Rise in serum creatinine ≥133 μM or ≥1.5 times premorbid level 1
- Advanced age and significant comorbidities may also indicate severe disease 1
First-Line Antibiotic Therapy
Vancomycin (Preferred)
- Dose: 125 mg orally four times daily for 10 days 1, 2
- Vancomycin is superior to metronidazole in severe CDI 3
- Can be administered with or without food 4
Fidaxomicin (Alternative)
- Dose: 200 mg orally twice daily for 10 days 1, 4
- Associated with fewer recurrences compared to vancomycin 1
- FDA-approved for C. difficile-associated diarrhea 4
- More expensive but may be preferred in patients at high risk for recurrence (elderly, multiple comorbidities, concurrent antibiotics) 3
Critical Point: Avoid Metronidazole
Metronidazole should be limited to mild-moderate CDI only and is NOT recommended for severe disease. 3 Repeated or prolonged courses carry risk of cumulative and potentially irreversible neurotoxicity. 3, 2
Fulminant CDI (Life-Threatening Disease)
If the patient progresses to fulminant colitis with any of the following:
- Hypotension or shock
- Ileus or toxic megacolon
- Perforation
- Severe abdominal tenderness with systemic toxicity 3
Treatment escalation required:
- High-dose oral vancomycin 500 mg four times daily PLUS intravenous metronidazole 500 mg every 8 hours 2
- Early surgical consultation is mandatory 3, 1
- Consider vancomycin enemas (500 mg in 100-500 mL saline per rectum every 6 hours) if ileus prevents oral medication from reaching the colon 3
Essential Supportive Measures
Discontinue Inciting Factors
- Stop the causative antibiotic immediately if possible 3, 1
- Continued antibiotic use significantly increases recurrence risk 3
- If antibiotics must be continued for another infection, use agents less associated with CDI: parenteral aminoglycosides, sulfonamides, macrolides, vancomycin, or tetracycline/tigecycline 3
Aggressive Resuscitation
- Intravenous fluid resuscitation for volume depletion from diarrhea 3
- Electrolyte replacement 3
- Albumin supplementation if serum albumin <2 g/dL 3
- Early ICU monitoring for fulminant cases 3
Avoid Harmful Medications
Adjunctive Therapy for High-Risk Patients
Bezlotoxumab (monoclonal antibody against C. difficile toxin B) may prevent recurrences, particularly in:
- Patients with CDI due to 027 epidemic strain 3
- Immunocompromised patients 3
- Patients with severe CDI 3
Surgical Management
Indications for surgery include: 3, 1
- Perforation of the colon
- Systemic inflammation with deteriorating clinical condition despite medical therapy
- Toxic megacolon
- Severe ileus
- Peritonitis
Surgical options:
- Total colectomy (traditional approach) 3
- Diverting loop ileostomy with colonic lavage (emerging alternative with potentially lower mortality) 3
- Loop ileostomy with antegrade vancomycin flushes via ileostomy has shown 93% colon preservation rate 3
Infection Control
Hand hygiene with soap and water is essential - alcohol-based sanitizers do not kill C. difficile spores. 1
Common Pitfalls to Avoid
- Do not use metronidazole for severe CDI - it has lower cure rates and should be reserved for mild-moderate disease only 3, 1
- Do not delay surgical consultation - early involvement improves outcomes in fulminant cases 3, 1
- Do not continue the inciting antibiotic unless absolutely necessary for life-threatening infection 3, 1
- Do not use antidiarrheals - they can precipitate toxic megacolon 1
- Do not assume clinical improvement means treatment failure - response may take 3-5 days 2