What is the treatment for Clostridioides (C.) difficile colitis?

Treatment of Clostridioides difficile Colitis

For initial C. difficile infection, oral vancomycin 125 mg four times daily for 10 days is the first-line treatment regardless of disease severity, with fidaxomicin 200 mg twice daily for 10 days as an effective alternative that reduces recurrence rates. 1, 2

Disease Severity Assessment

Before initiating treatment, assess disease severity using these criteria:

Non-severe CDI is characterized by: 1

• Stool frequency < 4 times daily
• WBC < 15 × 10^9/L
• Normal serum albumin and creatinine
• No signs of severe colitis

Severe CDI is defined by one or more of: 1

• Fever > 38.5°C
• Marked leukocytosis (WBC > 15 × 10^9/L)
• Serum albumin < 30 g/L
• Rise in serum creatinine (≥1.5 times baseline)
• Hemodynamic instability
• Signs of peritonitis or ileus
• Pseudomembranous colitis on endoscopy

Initial Episode Treatment

Non-Severe CDI

Preferred regimen: Vancomycin 125 mg orally four times daily for 10 days 1, 2, 3

Alternative options: 1, 2

• Fidaxomicin 200 mg orally twice daily for 10 days (lower recurrence rates but higher cost) 4
• Metronidazole 500 mg orally three times daily for 10 days (acceptable for first episode only, but increasing treatment failures limit its use) 1, 2

Severe CDI

First-line: Vancomycin 125 mg orally four times daily for 10 days 1, 2

Alternative: Fidaxomicin 200 mg orally twice daily for 10 days (particularly valuable due to lower recurrence rates in severe disease) 1, 2, 4

Fulminant CDI

For patients with hypotension, shock, ileus, toxic megacolon, or peritonitis: 2

Medical regimen: 2

• Vancomycin 500 mg orally four times daily PLUS
• Intravenous metronidazole 500 mg three times daily

If oral administration not possible: 2

• Vancomycin 500 mg in 100 mL normal saline four times daily via nasogastric tube or retention enema PLUS
• Intravenous metronidazole 500 mg three times daily

Surgical consultation: Obtain early for patients with perforation, systemic inflammation not responding to antibiotics, toxic megacolon, or severe ileus 1. Surgery should be performed before colitis becomes very severe, ideally before serum lactate exceeds critical thresholds 1. Subtotal colectomy with end ileostomy is the established procedure, though loop ileostomy with colonic lavage is emerging as a colon-salvage alternative 2.

Recurrent CDI Management

First Recurrence

Treat based on severity: 1, 5

• Vancomycin 125 mg four times daily for 10 days (especially if metronidazole was used initially) 2, 5
• Fidaxomicin 200 mg twice daily for 10 days (preferred when vancomycin was used for first episode due to lower recurrence rates) 2, 5
• Avoid metronidazole for recurrent episodes due to lower sustained response rates and risk of cumulative neurotoxicity 2

Second and Subsequent Recurrences

Vancomycin tapered and pulsed regimen: 1, 2

• 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

Alternative: Fecal microbiota transplantation (FMT) for multiple recurrences 2, 5

Adjunctive therapy: Consider bezlotoxumab (monoclonal antibody against C. difficile toxin B) to prevent recurrences in high-risk patients 5, 6

Critical Adjunctive Measures

Discontinue inciting antibiotics as soon as clinically possible to reduce recurrence risk 1, 2, 5

Avoid: 1, 5

• Antiperistaltic agents and opiates
• Repeated or prolonged metronidazole courses (risk of irreversible neurotoxicity) 2

Infection control: 1, 5

• Hand hygiene with soap and water (alcohol-based sanitizers are ineffective against C. difficile spores)
• Contact precautions

Monitoring Response

Assess clinical response within 3 days of treatment initiation 1, 5

Treatment failure is defined as absence of improvement after 3-5 days 1, 5

No follow-up stool testing is needed if symptoms resolve 5

Pediatric Considerations (≥6 months old)

Non-severe or first recurrence: 2

• Vancomycin 10 mg/kg/dose (max 125 mg) four times daily for 10 days, or
• Metronidazole 7.5 mg/kg/dose (max 500 mg) four times daily for 10 days

Severe or fulminant: 2

• Vancomycin 10 mg/kg/dose (max 500 mg) every 8 hours for 10 days, with or without IV metronidazole

Multiple recurrences: 2

• Vancomycin extended regimen (weight-adjusted) or
• Consider FMT

Key Clinical Pitfalls to Avoid

Do not treat asymptomatic carriers with antibiotics 7

Do not use oral vancomycin for systemic infections - it is not absorbed and only effective for intraluminal C. difficile 3

Do not delay surgical consultation in fulminant cases - early intervention improves outcomes despite high overall mortality 6, 8

Fidaxomicin advantages: Lower recurrence rates compared to vancomycin, particularly valuable in high-risk patients, though cost may be higher 2, 9