Large Intestine: Clostridioides difficile Colitis

Definitions

• Formerly “Clostridium difficile”
• Clostridioides difficile Colitis – Colon Infection Due to Clostridioides difficile Bacteria
• Clostridioides difficile Enteritis – Small Intestine Infection Due to Clostridioides difficile Bacteria

Basics

• Gram Positive, Spore-Forming Bacillus
• Transmission: Fecal-Oral
• Readily Cultured in the Hospital Environment
• Produces Two Exotoxins
  • Toxin A & Toxin B
  • Mediates Diarrhea & Colitis
• NAP1/BI/027 Strain – Hypervirulent/Epidemic Strain Associated with Multiple Outbreaks
• Most Common Site: Distal Colon
• Mucosal Disease with PMN Inflammation of Mucosa & Submucosa
  • Exterior May Appear Normal at Time of Surgery Despite Aggressive Disease

Risk Factors

• ABX Use – Most Common Cause
  • Most Commonly Implicated ABX: Clindamycin #1, Fluoroquinolones & Cephalosporins
  • Typically Occur within 2 Weeks of Use but Can Occur > 3-5 Weeks After
• Age > 65
• Hospitalization & ICU Stay
• Severe Comorbid Illness
• Female Gender
• Gastric Acid Suppression
• Enteral Feeding
• GI Surgery
• Obesity
• IBD
• Chemotherapy

Presentation

• Symptoms:
  • Watery Diarrhea (≥ 3 Stools/24 Hours)
    • May Have Mucous or Occult Blood
  • Abdominal Pain
  • Fever
  • Nausea
• Non-Severe Disease – Stable, Afebrile & Mild Symptoms with WBC ≤ 15,000 cells/dL
• Severe Disease – Symptomatic with Fever, WBC > 15,000 cells/mL or Cr ≥ 1.5 mg/dL
• Fulminant Disease – Characterized by Ileus, Hypotension/Shock or Megacolon
  • Toxic Megacolon – *See Large Intestine: Toxic Megacolon
• Recurrent Disease – Recurrence of Symptoms within 2-8 Weeks After Treatment Stopped
  • Must Have Seen Resolution of Symptoms While On Appropriate Therapy

Diagnosis

• Dx: Stool Test for Toxin A/B by ELISA (Enzyme-Linked Immunoassay)
  • Other Options with Higher Sensitivity:
    • NAAT (Nucleic Acid Amplification Testing)
    • Toxigenic Culture
    • Glutamate Dehydrogenase Stool Test
• Colonoscopy May Show Pseudomembranes (Pseudomembranous Colitis) – Suggestive but Not Diagnostic

ABX Options & Dosing

• Vancomycin
  • Oral 125 mg – Every 6 Hours for 10 Days
  • High-Dose: Oral 500 mg Every 6 Hours
  • Not Given IV (Does Not Cross GI Membrane)
• Metronidazole (Flagyl)
  • Oral 500 mg – Every 8 Hours for 10 Days
  • IV 500 mg – Every 8 Hours for 10 Days
• Fidaxomicin
  • Newer Expensive Agent
  • Oral 200 mg – Every 12 Hours for 10 Days

Treatment

• Treatment Options are Controversial & Debated
• Non-Severe/Severe Disease:
  • Initial Episode: Vancomycin
    • Other Options:
      • Fidaxomicin
      • Metronidazole – Only if Non-Severe
  • First Recurrence:
    • Previously on Vancomycin: Vancomycin (Pulse & Taper) or Fidaxomicin
    • Previously on Metronidazole or Fidaxomicin: Vancomycin
  • Options for Subsequent Recurrences/Refractory Disease:
    • Fecal Microbiota Transplant – Many Prefer if Available
    • Vancomycin (Pulse & Taper)
    • Vancomycin Followed by Rifaximin
    • Fidaxomicin
• Fulminant Disease:
  • Tx: Combined ABX (High-Dose Vancomycin & IV Flagyl)
  • Add Rectal Vancomycin Enema if Ileus Present
  • Low Threshold for Surgery
• Surgery:
  • Procedure: Total Colectomy & Ileostomy
    • Segmental Resection Contraindicated Even if Believed to Be Confined to a Localized Area
  • Indications:
    • Absolute:
      • Toxic Megacolon
      • Perforation
      • Peritonitis
    • Relative:
      • Fulminant Disease
      • Medical Failure
      • Worsening Clinical Course