Which infection causes pseudomembranous colitis?

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Last updated: October 1, 2026 • View editorial policy

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Clostridioides difficile (C. difficile) causes pseudomembranous colitis

Clostridioides difficile infection (CDI) is the causative organism of pseudomembranous colitis, characterized by white or yellowish plaques covering the colonic mucosa. 1, 2

Key Diagnostic Features

The infection presents with:

  • Pseudomembranes: White or yellowish plaques on colonoscopy that are pathognomonic for CDI 3
  • Three or more episodes of unexplained, unformed stools in 24 hours (in patients not taking laxatives) 4
  • Risk factors include recent healthcare exposure, antibiotic use (especially clindamycin), and immunosuppression 4

Diagnostic Approach

Testing should utilize a 2-step algorithm 1:

  1. Enzyme immunoassays for glutamate dehydrogenase (GDH) and toxins A and B, OR
  2. Nucleic acid amplification testing (NAAT/PCR) for toxin genes

Important caveat: Do not test asymptomatic patients or perform "test of cure" after treatment, as >60% remain C. difficile positive even after successful treatment 1. Testing for recurrent symptoms should ideally include toxin detection 1.

Age-Specific Testing Considerations

  • Infants ≤12 months: Never routinely test due to >40% asymptomatic colonization rate 1
  • Children 1-2 years: Test only after excluding other causes 1
  • Children ≥2 years: Test those with prolonged diarrhea plus risk factors (IBD, immunocompromise, healthcare exposure, recent antibiotics) 1

Important Clinical Pitfall

While C. difficile causes the vast majority of pseudomembranous colitis cases, other etiologies exist 5. If endoscopy shows pseudomembranes but C. difficile testing is negative, or if presumed CDI doesn't respond to treatment, consider:

  • Cytomegalovirus (CMV) colitis (can occur concomitantly with CDI) 3
  • Other clostridial species (rare) 6
  • Ischemic colitis (can mimic or coexist with CDI) 3

Histologic review of colonic biopsy specimens can provide diagnostic clues when C. difficile testing is negative 5.

References

4
Research

Clostridioides difficile Infection: Update on Management.

American family physician, 2020

5
Research

Pseudomembranous colitis: Not always Clostridium difficile.

Cleveland Clinic journal of medicine, 2016

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.