What is pseudomembranous colitis?

Pseudomembranous Colitis: Definition, Diagnosis, and Management

Pseudomembranous colitis is an inflammatory condition of the colon characterized by the formation of elevated yellow-white plaques (pseudomembranes) on the colonic mucosa, most commonly caused by Clostridioides (Clostridium) difficile infection following antibiotic use. 1

Pathophysiology and Etiology

Pseudomembranous colitis occurs when:

• C. difficile proliferates in the colon after disruption of normal gut microbiota, typically due to antibiotic therapy
• The bacteria produce toxins (primarily toxin A and B) that:
  • Disrupt epithelial integrity via microtubules and cell-cell tight junctions
  • Trigger cytokine release (e.g., IL-8)
  • Promote inflammatory infiltrate in the colonic mucosa
  • Cause fluid shifts leading to diarrhea
  • Lead to epithelial necrosis 2

While C. difficile is responsible for the vast majority of cases, other less common causes include:

• Other infectious organisms (bacteria, parasites, viruses)
• Inflammatory bowel disease
• Ischemic colitis
• Behcet's disease
• Collagenous colitis
• Certain drugs and toxins 1

Risk Factors

The primary risk factors include:

• Recent antibiotic therapy (especially β-lactams, clindamycin, fluoroquinolones) 3
• Advanced age (≥65 years) 2
• Prolonged hospitalization 2
• Immunosuppression 2
• Proton pump inhibitor use 2
• Chronic kidney disease 2
• Use of feeding tubes 2
• Chemotherapy 2

Clinical Presentation

Typical symptoms include:

• Watery diarrhea (usually non-bloody)
• Abdominal pain and cramping
• Fever
• Leukocytosis
• Hypoalbuminemia 4, 1

Severe complications may include:

• Toxic megacolon
• Colonic perforation
• Acute peritonitis
• Septic shock 2, 5

Diagnostic Approach

The diagnosis of pseudomembranous colitis requires:

1. Clinical symptoms: Presence of diarrhea (≥3 unformed stools in 24 hours) 2

2. Laboratory testing:

   • Stool tests for toxigenic C. difficile or its toxins
   • Elevated WBC count (>15 × 10^9/L) may indicate severe disease
   • Elevated serum creatinine (>50% above baseline)
   • Hypoalbuminemia
   • Elevated serum lactate in severe cases 2

3. Endoscopic findings:

   • Visualization of pseudomembranes (yellow-white plaques) on colonoscopy or sigmoidoscopy
   • Flexible sigmoidoscopy should be considered when stool tests are negative but clinical suspicion remains high 2

4. Imaging findings (particularly in severe cases):

   • CT findings: colonic wall thickening, dilation, pericolonic stranding, "accordion sign," "double-halo sign," and ascites
   • Ultrasound may be useful in critically ill patients who cannot be transported for CT 2

Management

Treatment should be guided by disease severity:

1. Mild-to-moderate disease:

   • Discontinue the inciting antibiotic if possible 2
   • Oral metronidazole 500 mg three times daily for 10 days 2

2. Severe disease:

   • Oral vancomycin 125 mg four times daily for 10 days 2
   • If oral therapy is impossible: intravenous metronidazole 500 mg three times daily plus intracolonic vancomycin 500 mg in 100 mL normal saline every 4-12 hours 2

3. Fulminant disease/surgical indications:

   • Colectomy should be performed in cases of:
     • Colonic perforation
     • Systemic inflammation not responding to antibiotics
     • Toxic megacolon
     • Severe ileus 2

4. Recurrent disease:

   • For first recurrence: same treatment as initial episode
   • For second or subsequent recurrences: vancomycin with tapered/pulsed regimen 2

Prevention

Key preventive measures include:

• Judicious use of antibiotics
• Careful hand washing
• Environmental decontamination
• Enteric isolation precautions for infected patients 4, 6
• Discontinuation of unnecessary proton pump inhibitors 2

Clinical Pearls and Pitfalls

• A "test of cure" is not recommended as patients may asymptomatically shed C. difficile spores for up to six weeks after successful treatment 2
• Antiperistaltic agents and opiates should be avoided as they may worsen the condition 2
• Post-infectious irritable bowel syndrome may occur in approximately 4% of patients following CDI, which should not be confused with recurrent infection 2
• Empiric therapy should be initiated when clinical suspicion is high, even before laboratory confirmation 2
• Vancomycin use should be limited to severe cases to prevent development of vancomycin-resistant organisms 6