Clostridium difficile infection

Epidemiology

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Etiology

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Risk factors for CDI

• Recent antibiotic treatment
  • Antibiotics destroy the normal intestinal bacterial flora that normally suppresses C. difficile overgrowth. C. difficile is resistant to most of the commonly used antibiotics.
  • High-risk antibiotics (odds ratio ≥ 5)
    • Clindamycin c
    • Cephalosporins
    • Fluoroquinolones
• Advanced age
• Gastric acid suppression (e.g., with proton pump inhibitors) or bypass (e.g., enteral feeding) c
  • C difficile spores are acid resistant, but proton pump inhibitors (PPIs) are thought to alter the colonic microbiome, which increases the risk for C difficile proliferation.
• Recent hospitalization

Pathophysiology

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• Toxin A (enterotoxin): binding to brush border of enterocytes → disruption of actin cytoskeleton functioning → increase in epithelial permeability and apoptosis → diarrhea
• Toxin B (cytotoxin): same as in toxin A, but can also cause pore formation within the endosomal membrane via insertion of the translocation domain → release of endosomal content into the cytosol → cytopathic effect
• Mucosal Injury & Inflammation
  • Toxins bind to intestinal epithelial cell receptors
  • Trigger inflammatory cascade: neutrophil recruitment, cytokine release (IL-8, TNF-α)
  • Results in pseudomembranous colitis: yellow-white plaques (pseudomembranes) composed of fibrin, mucin, necrotic epithelial cells, and inflammatory cells

Clinical features

• Watery diarrhea (≥3 loose stools in 24 hours).
• Lower abdominal cramping and tenderness.
• Systemic symptoms: Fever, leukocytosis, dehydration.
• Severe/Fulminant presentation: Hypotension, shock, ileus, toxic megacolon.

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Diagnostics

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• Initial/Screening: Stool toxin assay (EIA) or NAAT/PCR for C. diff toxin gene (only test symptomatic patients).
• Key Labs:
  • WBC count (severe if WBC > 15,000/µL).
  • Serum creatinine (severe if Cr > 1.5 mg/dL or >1.5x baseline).
• Imaging: Abdominal X-ray or CT scan if fulminant symptoms suspected; look for colonic dilation, wall thickening, or “thumbprinting”.
• Endoscopy/Biopsy: Sigmoidoscopy/colonoscopy (usually not needed unless diagnosis unclear) showing pseudomembranous colitis (adherent yellow-white plaques on erythematous mucosa).

Treatment

• Initial Step: Discontinue the inciting antibiotic if possible. Avoid antimotility agents (e.g., loperamide).
• First-line (Non-severe & Severe initial episode):
  • Fidaxomicin PO 200 mg BID for 10 days (preferred). c
  • Vancomycin PO 125 mg QID for 10 days (acceptable alternative).
• Fulminant (Hypotension, shock, ileus, megacolon):
  • IV Metronidazole (500 mg Q8h) PLUS high-dose oral/rectal Vancomycin (500 mg PO/PR Q6h).
• First Recurrence:
  • If Vancomycin used for initial episode: Fidaxomicin PO or Vancomycin tapered and pulsed regimen.
  • If Fidaxomicin used for initial episode: Vancomycin tapered and pulsed regimen.
• Subsequent Recurrences:
  • Vancomycin taper/pulsed regimen, or Fidaxomicin, or oral Vancomycin followed by rifaximin.
  • Consider fecal microbiota transplant (FMT).
  • Monoclonal antibody: Bezlotoxumab (binds toxin B) can be added to standard Abx to reduce recurrence.
• Refractory/Toxic Megacolon: Urgent subtotal colectomy or diverting loop ileostomy.