Pseudomembranous Colitis

Definition

Pseudomembranous colitis (PMC) is a severe form of Clostridioides difficile infection (CDI) — the most common health care-associated diarrheal illness. It is characterized by the formation of pseudomembranes on the colonic mucosa resulting from toxin-mediated mucosal injury. While other organisms (Salmonella, C. perfringens type A, S. aureus) can cause antibiotic-associated diarrhea, only C. difficile causes pseudomembrane formation.

Etiology

Feature	Detail
Organism	Clostridioides difficile — obligate anaerobe, gram-positive, spore-forming bacillus
Reservoir	Environmental surfaces, hospital settings; spores persist for months
Transmission	Fecal–oral via spore ingestion; hands of healthcare workers
Colonization rate	1–3% community; up to 20–30% of hospitalized adults

Risk Factors

Antibiotic use — nearly any antibiotic; highest risk with clindamycin, 2nd/3rd-gen cephalosporins, fluoroquinolones
Age >65 years
Hospitalization / nursing home residence
Gastrointestinal surgery
Immunosuppression
Proton pump inhibitor use (modest risk, especially if already on antibiotics)
Enteral tube feeding

Pathogenesis

Three events are required for CDI to develop:

Antibiotic exposure → disrupts normal colonic microbiota, creating colonization susceptibility
Exposure to toxigenic C. difficile → spores survive gastric acid, germinate in small bowel, colonize the colon
Host factors → inadequate immune response (low IgG anti-toxin A/B), virulent strain (e.g., NAP1/BI/027)

Toxins

Toxin	Type	Mechanism
Toxin A	Enterotoxin	Potent neutrophil chemoattractant; glucosylates Rho GTPases
Toxin B	Cytotoxin	Primary virulence factor; glucosylates Rho GTPases → disrupts actin cytoskeleton → tight junction loss, fluid leakage
Binary toxin (CDT)	—	Present in hypervirulent NAP1/BI/027 strain; role in pathogenesis still being defined

Downstream effects: epithelial cytoskeletal disruption → tight junction barrier loss → cytokine release → apoptosis → neutrophil infiltration → pseudomembrane formation.

Morphology

Gross / Endoscopic

Pseudomembranes begin as 1–2 mm whitish-yellow plaques on colonic mucosa
Intervening mucosa initially appears normal
Progress to confluent plaques coating the entire colon wall
Whole colon involved; ~10% show rectal sparing
Terminal ileum typically spared

Histology — Pathognomonic "Volcano Lesion"

Surface epithelium is denuded
Superficial lamina propria: dense neutrophil infiltrate + fibrin thrombi in capillaries
Damaged crypts distended by mucopurulent exudate that erupts through the surface — the classic "volcanic eruption" pattern
Pseudomembranes = adherent layer of necrotic leukocytes, fibrin, mucus, and cellular debris

C. difficile colitis — endoscopic (A), gross specimen (B), and "volcano lesion" histology (C)

Fig. from Robbins, Cotran & Kumar Pathologic Basis of Disease — (A) Endoscopic view of gray pseudomembranes. (B) Gross specimen. (C) Volcano lesion: neutrophils erupting from a damaged, dilated crypt.

Clinical Features

Symptom/Sign	Notes
Watery diarrhea	Most common presenting symptom
Abdominal cramping / pain	Common
Fever + leukocytosis	Especially in severe disease
Dehydration	Significant in moderate-severe disease
Hypoalbuminemia	From protein loss in severe cases
Fecal leukocytes / occult blood	May be present
Grossly bloody diarrhea	Uncommon

Fulminant CDI

May present WITHOUT diarrhea — mimics acute surgical abdomen
Sepsis (hypotension, fever, tachycardia, leukocytosis ≥20,000 WBCs/μL)
Toxic megacolon — potentially fatal
CT abdomen: colon-wall thickening, ileus, ascites

Diagnosis

Nucleic acid amplification test (NAAT) — highly sensitive; positive NAAT alone = colonization
Stool toxin assay — both NAAT positive + toxin positive = CDI (symptomatic disease)
Sigmoidoscopy/colonoscopy — to visualize pseudomembranes (especially in fulminant disease without diarrhea)
Abdominal CT — for fulminant/surgical abdomen presentations

Treatment

Non-severe / Initial Episode

Agent	Notes
Vancomycin (oral)	First-line for non-severe and severe CDI
Fidaxomicin	Preferred; lower recurrence rate than vancomycin
Metronidazole	No longer recommended as first-line; not for recurrent CDI

Severe / Fulminant CDI

Oral vancomycin + IV metronidazole (for ileus/inability to deliver oral therapy)
Vancomycin per retention enema
Surgical colectomy if no response to medical therapy — perform before serum lactate reaches 5 mmol/L

Recurrent CDI (~15–40% of patients)

Fidaxomicin (superior to vancomycin for recurrence prevention)
Vancomycin in tapering/pulsed regimen
Fecal Microbiota Transplantation (FMT) — highly effective for recurrent disease; available as nasoduodenal tube, colonoscope, enema, or oral capsules
FDA-approved microbiota products: Rebyota (live-jslm, suspension) and Vowst (live-brpk, oral spore suspension)
Bezlotoxumab — monoclonal antibody against toxin B; adjunctive agent that reduces recurrence risk by ~10% absolute in high-risk patients

Complications

Complication	Note
Toxic megacolon	Marked colonic wall injury; potentially fatal
Colonic perforation	Surgical emergency
Sepsis / septic shock	Especially in fulminant disease
Recurrent CDI	Up to 40%; each recurrence increases risk of further episodes

Key Points Summary

PMC is the severe end of C. difficile infection, defined by pseudomembrane formation on colonoscopy/pathology
Pathognomonic histology: "volcano lesion" — mucopurulent exudate erupting from dilated crypts
Toxin B is the primary virulence factor; toxin A is a potent neutrophil chemoattractant
Antibiotic disruption of the microbiome is the essential first step
Fidaxomicin is preferred over vancomycin for lower recurrence
FMT is increasingly accepted for recurrent disease, with two FDA-approved commercial products now available

Sources: Harrison's Principles of Internal Medicine 22E (2025); Robbins, Cotran & Kumar Pathologic Basis of Disease; Robbins & Kumar Basic Pathology

This is a shared conversation. Sign in to Orris to start your own chat.