What is the recommended treatment for pseudomembranous colitis?

Treatment of Pseudomembranous Colitis

For pseudomembranous colitis (Clostridioides difficile infection), oral vancomycin 125 mg four times daily for 10 days is the preferred treatment for severe disease, while oral metronidazole 500 mg three times daily for 10 days is recommended for mild-to-moderate disease. 1, 2

Disease Severity Classification

Before initiating treatment, classify disease severity to guide antibiotic selection 1:

Severe CDI is defined by one or more of the following:

• Marked leukocytosis (WBC >15 × 10⁹/L) 1
• Decreased serum albumin (<30 g/L) 1
• Rise in serum creatinine (≥133 μM or ≥1.5 times baseline) 1
• Fever >38.5°C, hemodynamic instability, or signs of peritonitis 1
• Pseudomembranous colitis on endoscopy 1
• Colonic distension or wall thickening on imaging 1

Initial Treatment Algorithm

Mild-to-Moderate Disease (Oral Therapy Possible)

• Metronidazole 500 mg orally three times daily for 10 days 1
• This remains first-line despite emerging data suggesting potential inferiority to vancomycin, primarily due to cost considerations 1

Severe Disease (Oral Therapy Possible)

• Vancomycin 125 mg orally four times daily for 10-14 days 1, 2
• The 125 mg dose is as effective as higher doses (500 mg) with equivalent cure rates of approximately 80-81% 2
• Higher doses (up to 500 mg four times daily) may be considered but offer no proven additional benefit 1

Severe Disease When Oral Therapy Impossible

This represents a critical clinical scenario requiring aggressive multimodal therapy:

• Metronidazole 500 mg IV every 8 hours 1
• PLUS vancomycin 500 mg in 100 mL normal saline per rectum (retention enema) every 4-12 hours 1
• AND/OR vancomycin 500 mg four times daily via nasogastric tube 1

The combination approach is essential because parenteral vancomycin does not achieve adequate colonic concentrations 2, while oral/rectal vancomycin achieves fecal concentrations >3100 mg/kg 2.

Critical Supportive Measures

Immediately discontinue the precipitating antibiotic if clinically feasible 1

Avoid antiperistaltic agents and opiates as they may precipitate toxic megacolon 1

For mild CDI clearly induced by antibiotics, consider stopping the offending agent and observing closely before initiating specific therapy 1, though this approach requires vigilant monitoring for clinical deterioration 1.

Recurrent Disease Management

First recurrence:

• Treat identically to initial episode based on severity (metronidazole for mild-moderate, vancomycin for severe) 1

Second or subsequent recurrences:

• Vancomycin 125 mg orally four times daily is preferred over metronidazole 1
• Fidaxomicin 200 mg orally twice daily for 10 days may be considered when recurrence risk is high, though cost is prohibitive for many patients 1
• Fecal microbiota transplantation (FMT) is associated with symptom resolution in recurrent CDI and should be strongly considered 1

Recurrence rates range from 18-25% even with appropriate initial therapy 2, and are more common in elderly patients, those with concomitant antibiotic use, comorbidities, proton pump inhibitor use, and severe initial disease 1.

Surgical Intervention Criteria

Colectomy should be performed urgently for: 1

• Perforation of the colon 1
• Toxic megacolon with systemic deterioration despite medical therapy 1
• Signs of peritonitis with hemodynamic instability 1

Subtotal colectomy is the procedure of choice with mortality rates of 14% compared to 100% for left hemicolectomy 3. The external appearance of the colon is often deceptively normal and should not influence the decision to perform subtotal rather than segmental resection 3.

Monitoring and Special Considerations

In patients >65 years of age, monitor renal function during and after treatment as nephrotoxicity risk is increased even with oral vancomycin 2

Monitor serum vancomycin concentrations in select patients: 2

• Those with renal insufficiency and/or active colitis
• Patients receiving concomitant aminoglycoside therapy
• Patients with inflammatory intestinal mucosa who may have significant systemic absorption 2

Assess treatment response by day 3 - expect decreased stool frequency or improved consistency without new signs of severe colitis 1. Metronidazole may require 3-5 days for clinical response 1.

Common Pitfalls to Avoid

Do not perform "test of cure" after CDI treatment as this is not recommended and may lead to unnecessary additional therapy 1

Do not use oral vancomycin for systemic infections - it is not absorbed and only effective for intestinal C. difficile 2

Do not delay surgical consultation in deteriorating patients - mortality increases dramatically when surgery is delayed in toxic megacolon 3

Do not assume normal external colonic appearance at laparotomy indicates limited disease - proceed with subtotal colectomy as planned 3