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

Treatment of Clostridium difficile Diarrhea

For initial episodes of C. difficile infection, oral vancomycin 125 mg four times daily for 10 days is the first-line treatment for both non-severe and severe disease. 1, 2

Disease Severity Assessment

Before initiating treatment, classify the infection as non-severe, severe, or fulminant based on specific clinical and laboratory criteria:

Non-severe CDI is characterized by: 1, 3

• Stool frequency <4 times daily
• White blood cell count ≤15,000 cells/mL
• Serum creatinine <1.5 mg/dL
• No signs of severe colitis

Severe CDI is defined by one or more of: 1, 2

• Temperature >38.5°C
• White blood cell count ≥15,000 cells/mL
• Serum creatinine rise >50% above baseline or >1.5 mg/dL
• Hemodynamic instability
• Elevated serum lactate
• Pseudomembranous colitis on endoscopy
• Colonic wall thickening or pericolonic fat stranding on imaging

Fulminant CDI includes: 1

• Hypotension or shock
• Ileus or toxic megacolon
• Signs of peritonitis

Treatment Algorithm for Initial Episode

Non-Severe Disease (Oral Therapy Possible)

First-line: Oral vancomycin 125 mg four times daily for 10 days 1, 2, 4

Alternative options: 1, 3

• Fidaxomicin 200 mg twice daily for 10 days (particularly useful for patients at high risk of recurrence) 5
• Metronidazole 500 mg three times daily for 10 days (less preferred, only in settings where vancomycin/fidaxomicin access is limited) 3

Severe Disease (Oral Therapy Possible)

First-line: 1, 2

• Fidaxomicin 200 mg twice daily for 10 days, OR
• Vancomycin 125 mg four times daily for 10 days

Fulminant Disease

Medical management: 1, 2

• High-dose oral vancomycin 500 mg four times daily PLUS
• IV metronidazole 500 mg every 8 hours

If ileus is present, add: 1

• Rectal vancomycin 500 mg in 100 mL normal saline every 6 hours as retention enema, AND/OR
• Vancomycin 500 mg four times daily via nasogastric tube 6

Treatment of Recurrent CDI

First Recurrence

Treat the same as the initial episode based on severity: 1, 2

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

Second and Subsequent Recurrences

Recommended approach: 6, 1, 2

• Vancomycin 125 mg four times daily for at least 10 days, followed by a tapered/pulsed regimen
• Example taper: decrease daily dose by 125 mg every 3 days 6
• Example pulse: 125 mg every 3 days for 3 weeks 6

For multiple recurrences after appropriate antibiotic therapy: 1, 2

• Consider fecal microbiota transplantation (FMT)

Surgical Management

Obtain surgical consultation early and perform colectomy for: 6, 1, 2

• Perforation of the colon
• Toxic megacolon or severe ileus
• Systemic inflammation with deteriorating clinical condition not responding to antibiotic therapy
• Serum lactate >5.0 mmol/L (operate before this threshold is exceeded)

Surgery should be performed before colitis becomes very severe to optimize outcomes. 6

Critical Management Principles

Discontinue inciting antibiotics: 1, 2, 3

• Stop the causative antibiotic as soon as possible
• If continued antibiotic therapy is required, switch to agents less associated with CDI

Avoid harmful agents: 6, 1, 2

• Never use antiperistaltic agents (loperamide) or opiates - these worsen outcomes and can precipitate toxic megacolon

Discontinue unnecessary medications: 1

• Stop proton pump inhibitors in patients at high risk for CDI

Monitor treatment response: 6, 1

• Expect improvement within 3 days (decreased stool frequency or improved consistency)
• If no improvement or clinical deterioration occurs, consider surgical consultation early

Common Pitfalls and Caveats

Metronidazole limitations: 1, 3

• Higher failure rates compared to vancomycin, especially in severe disease
• Factors associated with metronidazole failure: age >60 years, fever, hypoalbuminemia, peripheral leukocytosis, ICU stay, abnormal abdominal CT
• Avoid repeated or prolonged courses due to risk of cumulative and potentially irreversible neurotoxicity

Infection control: 1

• Use soap and water for hand hygiene - alcohol-based sanitizers are ineffective against C. difficile spores

Mild antibiotic-induced CDI: 6

• In clearly antibiotic-induced mild cases (stool frequency <4 times daily, no severe colitis signs), may consider stopping the inciting antibiotic and observing closely
• Place on therapy immediately if any clinical deterioration occurs