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Pseudomembranous Colitis

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Pseudomembranous Colitis

Pseudomembranous colitis is an inflammatory disease of the colon most commonly caused by toxin-producing Clostridioides difficile. It usually develops after antibiotic therapy disrupts the normal intestinal microbiota, allowing C. difficile to multiply and release toxins that cause watery diarrhea and colonic inflammation

Also called

Clostridioides difficile infection

ICD-10

A04.7

Specialty

Gastroenterology

Onset

Acute

Reviewed

July 2026

On This Page

Overview

Ulcerative colitis causes relapsing and remitting inflammation limited primarily to the inner lining of the colon. The disease typically starts in the rectum and spreads proximally in a continuous pattern. Patients may experience periods of active symptoms followed by remission. Diagnosis is based on clinical findings, stool testing, colonoscopy, and biopsy. Treatment aims to induce and maintain remission, heal the mucosa, prevent complications, and improve quality of life

Etiology & Risk Factors

Etiology

Pseudomembranous colitis is caused mainly by toxin-producing Clostridioides difficile.

Important bacterial toxins include:

  • Toxin A: enterotoxin

  • Toxin B: cytotoxin

  • Binary toxin in some highly virulent strains

Commonly Associated Antibiotics

  • Clindamycin

  • Cephalosporins

  • Fluoroquinolones

  • Broad-spectrum penicillins

  • Carbapenems

Almost any antibiotic can cause C. difficile infection.

Risk Factors

  • Recent or prolonged antibiotic use

  • Recent hospitalization

  • Residence in a nursing or long-term care facility

  • Advanced age

  • Previous C. difficile infection

  • Immunosuppression

  • Severe underlying illness

  • Gastrointestinal surgery

  • Prolonged healthcare exposure

  • Inflammatory bowel disease

  • Acid-suppressive medication, particularly when unnecessary

Pathophysiology

Antibiotic exposure disrupts the normal colonic microbiota, reducing resistance to colonization by C. difficile. Ingested spores survive gastric acid, reach the colon, and germinate into toxin-producing bacteria. Toxins damage colonic epithelial cells, disrupt tight junctions, and trigger intense neutrophilic inflammation. Fluid and electrolytes enter the intestinal lumen, causing watery diarrhea. Necrotic epithelial cells, mucus, fibrin, and inflammatory cells accumulate on the mucosal surface and form characteristic pseudomembranes. Severe inflammation may progress to ileus, toxic megacolon, perforation, sepsis, and shock

Clinical Presentation

Common Symptoms

  • Frequent watery diarrhea

  • Lower abdominal cramps

  • Abdominal tenderness

  • Fever

  • Nausea

  • Loss of appetite

  • Malaise

  • Dehydration

Severe or Fulminant Disease

  • Marked abdominal pain

  • Abdominal distension

  • High fever

  • Tachycardia

  • Hypotension

  • Reduced urine output

  • Ileus

  • Altered mental status

  • Toxic megacolon

  • Peritonitis

  • Septic shock

History Taking

  • Ask about:

    • Onset and frequency of diarrhea
    • Stool consistency
    • Presence of blood or mucus
    • Abdominal pain or distension
    • Fever or chills
    • Nausea or vomiting
    • Recent antibiotic use
    • Type and duration of antibiotics
    • Recent hospitalization
    • Nursing-home residence
    • Previous C. difficile infection
    • Immunosuppressive medication
    • Inflammatory bowel disease

Physical Examination

General Examination

Assess for:

  • Fever

  • Tachycardia

  • Hypotension

  • Dehydration

  • Pallor

  • Confusion

  • Sepsis or shock

Abdominal Examination

Look for:

  • Abdominal distension

  • Diffuse or lower abdominal tenderness

  • Tympany

  • Reduced bowel sounds in ileus

  • Guarding

  • Rebound tenderness

  • Signs of peritonitis

Investigations

Stool Testing

Test patients who have new, unexplained, clinically significant diarrhea, usually three or more unformed stools within 24 hours.

Available tests include:

  • Glutamate dehydrogenase antigen test

  • Toxin A and B enzyme immunoassay

  • Nucleic acid amplification test or PCR

  • Multistep testing algorithms combining antigen, toxin, and molecular tests

Only unformed stool should generally be tested. Testing asymptomatic patients may detect colonization rather than active infection.

Laboratory Tests

  • Complete blood count

  • C-reactive protein

  • Renal function and electrolytes

  • Serum albumin

  • Serum lactate

  • Liver function tests

  • Blood cultures if septic

  • Arterial or venous blood gas in severe disease

Possible findings include:

  • Leukocytosis

  • Acute kidney injury

  • Hypokalemia

  • Hypoalbuminemia

  • Elevated inflammatory markers

  • Metabolic acidosis

  • Elevated lactate

Imaging

Abdominal Radiograph

May show:

  • Colonic dilatation

  • Ileus

  • Toxic megacolon

  • Free air if perforation has occurred

CT Abdomen and Pelvis

Consider in severe or complicated disease.

Possible findings include:

  • Colonic wall thickening

  • Pericolic fat stranding

  • Mucosal edema

  • Ascites

  • Colonic dilatation

  • Toxic megacolon

  • Perforation

Endoscopy

Colonoscopy is not routinely required.

It may be considered when:

  • Stool tests are inconclusive

  • Another diagnosis is suspected

  • Rapid confirmation is essential

Typical findings include raised yellow-white pseudomembranes over inflamed colonic mucosa.

Endoscopy should be avoided in toxic megacolon or suspected perforation.

Diagnosis

Diagnosis

Diagnosis requires:

  • Compatible symptoms, particularly new-onset diarrhea

  • Positive testing for toxigenic C. difficile or its toxins

  • Exclusion of alternative causes when necessary

Severity Classification

Non-Severe Infection

  • Leukocytosis not exceeding approximately 15,000 cells/mm³

  • Serum creatinine below 1.5 mg/dL

Severe Infection

  • White blood cell count above 15,000 cells/mm³, or

  • Serum creatinine of at least 1.5 mg/dL

Fulminant Infection

One or more of:

    • Hypotension

    • Shock

    • Ileus

    • Toxic megacolon

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Management

General Measures

  • Stop the precipitating antibiotic whenever clinically possible

  • Stop unnecessary proton-pump inhibitors

  • Correct dehydration and electrolyte abnormalities

  • Avoid antimotility drugs such as loperamide

  • Monitor vital signs and urine output

  • Assess for ileus, megacolon, or perforation

  • Use contact precautions

  • Seek early surgical advice in fulminant disease

Initial Non-Fulminant Infection

Preferred treatment:

  • Oral fidaxomicin

Acceptable alternative:

  • Oral vancomycin

IDSA and SHEA suggest fidaxomicin rather than a standard course of vancomycin for an initial episode when available, while recognizing vancomycin as an acceptable alternative.

Metronidazole is generally not preferred when fidaxomicin or vancomycin is available.

Fulminant Infection

Management generally includes:

  • High-dose oral or nasogastric vancomycin

  • Intravenous metronidazole

  • Rectal vancomycin when severe ileus prevents adequate colonic drug delivery

  • Aggressive intravenous fluid resuscitation

  • Intensive monitoring

  • Immediate surgical consultation

Recurrent Infection

Options depend on previous treatment and recurrence history:

  • Fidaxomicin

  • Vancomycin taper-and-pulse regimen

  • Vancomycin followed by rifaximin in selected patients

  • Bezlotoxumab for selected patients at high risk of further recurrence

  • Fecal microbiota-based therapy after multiple recurrences despite appropriate antibiotics

IDSA and SHEA recommend considering fidaxomicin for recurrent infection and bezlotoxumab as an adjunct in selected patients with recurrence risk.

Surgical Management

Urgent surgery may be required for:

  • Toxic megacolon

  • Colonic perforation

  • Peritonitis

  • Bowel necrosis

  • Progressive shock

  • Worsening organ failure

  • Failure of maximal medical treatment

Procedures may include:

  • Subtotal colectomy with end ileostomy

  • Diverting loop ileostomy with colonic lavage in selected patients

Complications

  • Severe dehydration
  • Electrolyte abnormalities
  • Acute kidney injury
  • Hypoalbuminemia
  • Ileus
  • Toxic megacolon
  • Colonic perforation
  • Peritonitis
  • Sepsis
  • Septic shock
  • Recurrent infection
  • Multiorgan failure
  • Death

Prognosis

Most patients improve with appropriate antibiotic therapy and withdrawal of the precipitating antibiotic. Prognosis is worse in older adults, immunocompromised patients, those with severe leukocytosis or renal failure, and patients who develop ileus, toxic megacolon, perforation, or shock. Recurrence is common and becomes increasingly likely after each repeated episode.

Key Points / Clinical Pearls

  • Pseudomembranous colitis is usually caused by toxin-producing C. difficile.
  • Recent antibiotic exposure is the major risk factor.
  • Watery diarrhea, abdominal pain, fever, and leukocytosis are typical.
  • Test only patients with clinically significant unformed stools.
  • A positive molecular test alone may represent colonization if symptoms are absent.
  • Fidaxomicin is generally preferred for an initial non-fulminant episode when available.
  • Oral vancomycin remains an effective alternative.
  • Fulminant infection requires high-dose oral vancomycin, IV metronidazole, and urgent surgical assessment.
  • Avoid antimotility medications.
  • Toxic megacolon, perforation, peritonitis, or shock may require emergency colectomy.
  • Contact precautions and sporicidal environmental cleaning help prevent transmission.
  •  
  • Salen P, Stankewicz HA. National Center for Biotechnology Information (NIH). Pseudomembranous Colitis, StatPearls.
  • Johnson S, Lavergne V, Skinner AM, et al. Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults. Clin Infect Dis. 2021;73:e1029-e1044. PMID: 34164674.
  • McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the IDSA and SHEA. Clin Infect Dis. 2018;66:e1-e48. Clin Infect Dis.
  • MedlinePlus, National Library of Medicine (NIH). Pseudomembranous Colitis: Medical Encyclopedia.
  • National Center for Biotechnology Information (NIH). Clostridioides Difficile Infection, StatPearls.