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Clinician

Blog articles for clinicians and other medical professionals.

Understanding Pseudomembranous Colitis

March 26th, 2025

This article provides a comprehensive review of PMC, including its epidemiology, pathophysiology, risk factors, clinical presentation, diagnosis, treatment, and prevention strategies.

Epidemiology of Understanding Pseudomembranous Colitis

PMC incidence has risen dramatically over the past few decades due to the growing use of broad-spectrum antibiotics, the development of hypervirulent C. difficile strains, and the rise of healthcare-associated infections.

  • C. difficile infection (CDI) causes 15% to 25% of all cases of antibiotic-associated diarrhea.
  • This condition predominantly affects older adults, with individuals over age 65 years accounting for most severe cases.
  • Hospitalized patients and residents of long-term care facilities are at the highest risk.
  • Community-acquired PMC cases are increasing, particularly in younger patients without prior antibiotic exposure.
  • Hypervirulent strains, such as C. difficile ribotype 027 (NAP1/B1), have been associated with more severe disease, higher recurrence rates, and increased mortality.

Pathophysiology

The pathogenesis of PMC involves three main mechanisms:

Disruption of normal gut flora

  • Broad-spectrum antibiotics reduce microbial diversity, eliminating competing gut flora and allowing C. difficile spores to germinate and proliferate.
  • Antibiotics most commonly associated with PMC include clindamycin, cephalosporins, fluoroquinolones, and broad-spectrum penicillin.

Toxin production

  • C. difficile produces two main toxins:
    • Toxin A (enterotoxin): This causes fluid secretion, inflammation, and cell damage.
    • Toxin B (cytotoxin): This disrupts the cytoskeleton of colonic epithelial cells, leading to cell apoptosis and necrosis.
  • These toxins trigger an inflammatory cascade, leading to colonic wall damage and pseudomembrane formation.

Inflammatory response and pseudomembrane formation

  • The inflammatory response includes neutrophil infiltration and the release of pro-inflammatory cytokines.
  • Pseudomembranes are composed of fibrin, mucus, necrotic epithelial cells, and inflammatory debris, giving the characteristic appearance seen on colonoscopy.

Risk factors

Several factors increase the risk of developing PMC:

  • Antibiotic use: This is the most significant risk factor, particularly with clindamycin, cephalosporins, fluoroquinolones, and carbapenems.
  • Hospitalization: This increases exposure to C. difficile spores and antibiotic use.
  • Age: Patients over 65 years are at increased risk due to altered microbiota and immune function.
  • Comorbidities: Certain conditions such as chronic kidney disease, inflammatory bowel disease (IBD), cancer, and immunosuppression can increase this risk.
  • Gastric acid suppression: Proton pump inhibitors (PPIs) and H2 blockers have been associated with increased C. difficile infection risk.
  • Surgical and medical procedures: Recent gastrointestinal surgery or tube feeding may predispose patients to PMC.

Clinical presentation

PMC symptoms range from mild to severe and include:

  • Diarrhea: Watery, profuse, and sometimes containing mucus or blood may be present.
  • Abdominal pain: This typically involves cramping and is localized to the lower quadrants.
  • Fever: This is common in moderate to severe cases.
  • Leukocytosis: This occurs when there is marked elevation in white blood cell count.
  • Nausea and anorexia: This may be present but are less common.

Severe cases can progress to:

  • Toxic megacolon: This involves colonic dilation with a risk of perforation.
  • Perforation and peritonitis: This can lead to sepsis and multiorgan failure.
  • Septic shock: This occurs in severe fulminant colitis.

Diagnosis

PMC is diagnosed through clinical evaluation and stool testing.

Laboratory tests

  • Stool toxin testing:
  • Enzyme immunoassay (EIA): This detects toxins A and B but has lower sensitivity.
  • Nucleic acid amplification test (NAAT) (e.g., PCR): This is highly sensitive and specific for C. difficile toxin genes.
  • Glutamate dehydrogenase (GDH) Test: This is often used in combination with toxin assays.

Endoscopy

  • Flexible sigmoidoscopy or colonoscopy:
  • This reveals characteristic pseudomembranes — yellowish plaques on the colonic mucosa.
  • This is typically reserved for patients with negative stool tests but persistent symptoms.

Imaging

  • CT scan of the abdomen and pelvis:
  • This may show colonic wall thickening, pericolonic stranding, and the "accordion sign," which is suggestive of PMC.
  • This is used to assess complications such as toxic megacolon and perforation.

Treatment

Management includes stopping the inciting antibiotic, initiating specific therapy against C. difficile, and providing supportive care.

Antibiotic therapy

  • First-line therapy:
  • Vancomycin (oral): 125 mg four times daily for 10 days.
  • Fidaxomicin: 200 mg twice daily for 10 days; associated with lower recurrence rates.
  • Alternative therapy:
  • Metronidazole: 500 mg orally three times per day for 10 days (reserved for mild cases when vancomycin is unavailable).

Supportive care

  • Consider fluid and electrolyte replacement.
  • Avoid antimotility agents (e.g., loperamide) to prevent toxic megacolon.

Fecal microbiota transplantation (FMT)

  • This is used for recurrent PMC cases.
  • This restores normal gut microbiota through stool infusion from a healthy donor.

Surgery

  • This is indicated in patients with toxic megacolon, perforation, or severe colitis refractory to medical therapy.

Prevention

  • Antibiotic stewardship: Limit unnecessary antibiotic use.
  • Infection control:
  • Hand hygiene with soap and water (alcohol-based sanitizers are ineffective against C. difficile spores)
  • Contact precautions (gowns and gloves for infected patients)
  • Environmental decontamination with sporicidal disinfectants
  • Probiotics: This may help prevent CDI in high-risk patients, though evidence remains mixed.
  • Vaccination: Experimental vaccines targeting C. difficile toxins are under investigation.

PMC is a serious, often preventable condition caused by C. difficile overgrowth usually following antibiotic therapy. Early recognition, prompt treatment, and adherence to infection control measures are critical in reducing morbidity and mortality.

Clinicians must remain vigilant, particularly in hospitalized and immunocompromised patients, to prevent outbreaks and improve patient outcomes.