What is the treatment for colitis due to Clostridioides (C.) difficile toxin A/B detection?

Treatment of Clostridioides difficile Colitis

For C. difficile colitis, treatment depends on disease severity: oral vancomycin 125 mg four times daily for 10 days is the first-line therapy for severe disease, while oral metronidazole 500 mg three times daily for 10 days is appropriate for non-severe disease. 1, 2

Disease Severity Assessment

Before initiating treatment, you must classify the infection as non-severe or severe based on specific clinical and laboratory criteria 2:

Non-severe CDI:

• Stool frequency less than 4 times daily 1
• White blood cell count less than 15 × 10⁹/L 2, 3
• No signs of systemic toxicity 3

Severe CDI includes any of the following:

• Fever greater than 38.5°C with rigors 1
• Hemodynamic instability or signs of septic shock 1
• Signs of peritonitis (abdominal tenderness, rebound, guarding) 1
• Ileus with vomiting or absent stool passage 1
• Marked leukocytosis (WBC greater than 15 × 10⁹/L) 1
• Marked left shift (band neutrophils greater than 20%) 1
• Serum creatinine rise greater than 50% above baseline 1
• Elevated serum lactate 1
• Pseudomembranous colitis on endoscopy 1
• Colonic distension or wall thickening on imaging 1, 3

Initial Episode Treatment Algorithm

For non-severe disease with oral therapy possible:

• Metronidazole 500 mg orally three times daily for 10 days 1, 3
• This is a strong recommendation (A-I evidence) 1, 3
• If the infection was clearly induced by antibiotics, consider stopping the inciting antibiotic and observing closely; initiate therapy immediately if deterioration occurs 1

For severe disease with oral therapy possible:

• Vancomycin 125 mg orally four times daily for 10 days 1, 4
• This is a strong recommendation (A-I evidence) 1, 3
• Fidaxomicin 200 mg twice daily for 10 days is an alternative, particularly for patients at high risk for recurrence 5, 6

For patients unable to take oral therapy (non-severe):

• Metronidazole 500 mg intravenously three times daily for 10 days 1

For patients unable to take oral therapy (severe):

• Metronidazole 500 mg intravenously three times daily for 10 days PLUS 1
• Intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours and/or 1
• Vancomycin 500 mg four times daily by nasogastric tube 1

Recurrent Infection Treatment

First recurrence:

• Treat the same as the initial episode based on severity (metronidazole for non-severe, vancomycin for severe) 1, 3

Second and subsequent recurrences:

• Vancomycin 125 mg orally four times daily for at least 10 days 1, 2
• Consider a taper/pulse strategy: decrease daily dose by 125 mg every 3 days, or pulse dosing of 125 mg every 3 days for 3 weeks 1
• Fidaxomicin 200 mg twice daily for 10 days is an alternative 2, 5
• Fecal microbiota transplantation (FMT) is strongly recommended for multiple recurrences unresponsive to antibiotics, with 70-90% success rates 3, 7

Surgical Intervention Criteria

Colectomy should be performed urgently for: 1, 3

• Perforation of the colon 1, 3
• Toxic megacolon 1, 3
• Severe ileus 1, 3
• Systemic inflammation with deteriorating clinical condition not responding to antibiotic therapy 1
• Serum lactate exceeding 5.0 mmol/L (operate before this threshold is reached) 1, 3

Surgery should be performed early, before colitis becomes very severe, as this improves outcomes 1, 3.

Critical Management Principles

Avoid the following medications:

• Antiperistaltic agents (loperamide, diphenoxylate) and opiates must be avoided as they can precipitate toxic megacolon 1, 2
• Discontinue proton pump inhibitors if not medically necessary 2

Antibiotic stewardship:

• Discontinue the inciting antibiotic immediately if possible 1, 3
• Use antibiotics with the narrowest spectrum necessary 1

Monitoring considerations:

• Monitor serum vancomycin concentrations in patients with renal insufficiency, inflammatory bowel disorders, or those receiving concomitant aminoglycosides, as systemic absorption can occur 4
• In patients over 65 years of age, monitor renal function during and after treatment due to increased nephrotoxicity risk 4

Common Pitfalls to Avoid

• Do not use intravenous vancomycin for C. difficile colitis—it is not excreted into the colon and is ineffective 3, 4
• Do not repeat stool testing after treatment to assess response; clinical improvement (decreased stool frequency or improved consistency after 3 days) is the primary measure of success 1, 3
• Do not delay surgery in severe cases waiting for antibiotic response; early colectomy before severe deterioration improves outcomes 1, 3
• Teicoplanin 100 mg twice daily can replace oral vancomycin if available in your region 1, 3