Treatment of Clostridium difficile Diarrhea
Vancomycin 125 mg orally four times daily for 10 days is now the preferred first-line treatment for both non-severe and severe initial episodes of C. difficile infection, replacing metronidazole as the standard of care. 1, 2
Disease Severity Classification
Before initiating treatment, classify disease severity to guide therapy selection:
Non-severe CDI is characterized by:
Severe CDI is defined by one or more of:
- Temperature >38.5°C 1, 2
- Hemodynamic instability or signs of septic shock 1, 2
- Leukocyte count >15×10⁹/L 1, 2
- Serum creatinine rise >50% above baseline 1, 2
- Elevated serum lactate 1, 2
- Evidence of pseudomembranous colitis on endoscopy 1, 2
- Colonic wall thickening on imaging 1, 2
Initial Episode Treatment Algorithm
For Non-Severe CDI:
Primary recommendation: Vancomycin 125 mg orally four times daily for 10 days 1, 2, 4
Alternative option: Fidaxomicin 200 mg orally twice daily for 10 days 1, 5
Only if vancomycin/fidaxomicin unavailable: Metronidazole 500 mg orally three times daily for 10 days 1, 3
- This represents a major shift from older guidelines that recommended metronidazole first-line 1
- The 2018 IDSA/SHEA guidelines downgraded metronidazole based on randomized trials showing vancomycin's superiority (97% cure vs 84% with metronidazole, P<0.006) 1
For Severe CDI:
Primary recommendation: Vancomycin 125 mg orally four times daily for 10 days 1, 2, 4
Alternative option: Fidaxomicin 200 mg orally twice daily for 10 days, particularly for patients at high risk of recurrence 2, 5
For Fulminant CDI (hypotension, shock, ileus, or megacolon):
Combination therapy required:
- Vancomycin 500 mg orally four times daily for 10 days 2
- PLUS intravenous metronidazole 500 mg every 8 hours 2
- If ileus present, ADD rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema 2
- Consider vancomycin 500 mg four times daily via nasogastric tube if oral route compromised 1
Critical Management Principles
Discontinue the inciting antibiotic immediately whenever possible, as continued use decreases clinical response and increases recurrence rates 1, 2
Avoid antiperistaltic agents and opiates entirely as these worsen outcomes and can precipitate toxic megacolon 1, 6
Do not use metronidazole for repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity 1
Treatment of Recurrent CDI
First Recurrence:
Treat based on severity using the same algorithm as initial episodes 2
- Consider fidaxomicin 200 mg twice daily for 10 days as it reduces recurrence risk 1, 2
- Alternatively, vancomycin in a tapered and pulsed regimen 2
Second and Subsequent Recurrences:
Vancomycin 125 mg orally four times daily for at least 10 days, followed by a tapered and pulsed regimen 1, 2, 6
Example taper/pulse strategy:
Fecal microbiota transplantation should be considered for multiple recurrences that have failed appropriate antibiotic treatments 2
Surgical Management
Colectomy is indicated for:
- Perforation of the colon 1, 2, 6
- Toxic megacolon 1, 2, 6
- Severe ileus 1, 2, 6
- Systemic inflammation with deteriorating clinical condition not responding to antibiotic therapy 1, 2, 6
Timing is critical: Surgery should preferably be performed before serum lactate exceeds 5.0 mmol/L 1, 2
Common Pitfalls and How to Avoid Them
Do not delay empiric treatment in fulminant cases or when substantial laboratory delay is expected (>48 hours) 1
Hand hygiene requires soap and water, not alcohol-based sanitizers, as alcohol is ineffective against C. difficile spores 2
Discontinue unnecessary proton pump inhibitors in patients at high risk for CDI 2
Monitor treatment response by day 3: Expect decreased stool frequency or improved consistency; if no improvement occurs, reassess severity and consider escalating therapy 1
Avoid using metronidazole for severe disease as it has significantly higher failure rates compared to vancomycin 2