What is the recommended management for Clostridioides difficile (C diff) diarrhea?

Management of Clostridioides difficile Diarrhea

For C. difficile-associated diarrhea (CDAD), treatment should be stratified based on disease severity, with oral vancomycin 125 mg four times daily for 10 days as the preferred treatment for severe cases and fidaxomicin 200 mg twice daily for 10 days as an alternative, especially for patients at high risk of recurrence. 1, 2

Disease Severity Classification

Non-severe/Mild-to-moderate CDAD:

• Stool frequency < 4 times daily
• No signs of severe colitis
• WBC < 15 × 10⁹/L
• Serum creatinine < 1.5 times baseline

Severe CDAD (one or more of the following):

• WBC > 15 × 10⁹/L
• Serum albumin < 30 g/L
• Serum creatinine ≥ 1.5 times baseline
• Temperature > 38.5°C
• Signs of peritonitis
• Pseudomembranous colitis on endoscopy

Complicated/Fulminant CDAD:

• Hypotension or shock
• Ileus
• Toxic megacolon
• Perforation
• Need for ICU admission

First-Line Treatment Algorithm

1. Non-severe CDAD:

• First choice: Vancomycin 125 mg orally four times daily for 10 days 1, 2
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 2, 3
• If access to first-line agents is limited: Metronidazole 500 mg orally three times daily for 10 days 1, 2

2. Severe CDAD:

• First choice: Vancomycin 125 mg orally four times daily for 10 days 1, 4
• Alternative: Fidaxomicin 200 mg orally twice daily for 10 days 2, 3

3. Complicated/Fulminant CDAD with oral therapy possible:

• Vancomycin 500 mg orally four times daily plus
• Metronidazole 500 mg IV three times daily 1

4. Complicated/Fulminant CDAD with oral therapy impossible:

• Metronidazole 500 mg IV three times daily plus
• Vancomycin 500 mg via nasogastric tube four times daily and/or
• Vancomycin 500 mg in 100 mL normal saline as retention enema every 4-12 hours 1

Management of Recurrent CDAD

First Recurrence:

• Preferred: Fidaxomicin 200 mg twice daily for 10 days 2
• Alternative: Vancomycin 125 mg four times daily for 10 days 2

Second or Subsequent Recurrences:

• Vancomycin in a 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, 2
• OR Extended-pulsed fidaxomicin: 200 mg twice daily for 5 days, followed by once every other day for 20 days 2
• OR Fecal microbiota transplantation (FMT) after at least 2-3 recurrences with appropriate antibiotic treatment failures 2

Surgical Considerations

Consider colectomy for any of the following:

• Perforation of the colon
• Systemic inflammation not responding to antibiotic therapy
• Toxic megacolon or severe ileus
• Serum lactate > 5.0 mmol/L 1, 2

Critical Adjunctive Measures

1. Discontinue the inciting antibiotic if possible 1, 2, 5

   • All patients who had their offending antibiotics discontinued showed resolution of diarrhea by day 14, compared to only 59% of those who remained on antibiotics 5

2. Avoid antiperistaltic agents and opiates as they may mask symptoms and worsen disease 1, 2

3. Implement strict infection control measures:

   • Isolate patients
   • Hand hygiene with soap and water (alcohol-based sanitizers are less effective against C. difficile spores)
   • Environmental cleaning with sporicidal agents 2

4. Consider discontinuing proton pump inhibitors if not medically necessary 2

5. Do not perform repeat testing for cure if symptoms resolve 2

Special Populations

Elderly Patients (>65 years):

• Higher risk for recurrence and complications
• Monitor renal function during and after treatment with vancomycin 4
• Consider more aggressive therapy earlier in the treatment course 2

Immunocompromised Patients:

• Higher risk for recurrence
• Consider adjunctive bezlotoxumab 10 mg/kg IV once during antibiotic treatment 2

Pediatric Patients:

• Similar treatment options as adults with weight-based dosing
• Fidaxomicin 200 mg twice daily for children weighing ≥12.5 kg who can swallow tablets 2

Monitoring and Follow-up

• Monitor for symptom resolution
• Follow patients for at least 8 weeks after treatment to assess for recurrence
• If systemic antibiotics are required in the future, consider prophylactic low-dose vancomycin (125 mg daily) during and after the antibiotic course 2

The treatment landscape for C. difficile has evolved significantly, with recent guidelines moving away from metronidazole as first-line therapy due to increasing treatment failures and higher recurrence rates compared to vancomycin and fidaxomicin 2, 6.