Clostridioides difficile

Introduction

Clostridioides difficile (formerly Clostridium difficile) is a Gram-positive, spore-forming, anaerobic bacillus that causes antibiotic-associated diarrhoea and colitis. It arises due to disruption of normal intestinal flora, allowing C. difficile to proliferate and release toxins (primarily toxin A and B), resulting in intestinal inflammation and epithelial damage.

Peak Incidence

• Most common in individuals aged >65 years.
• Risk also increased in hospitalised patients, recent antibiotic users, and immunocompromised individuals.

Pathophysiology

• Antibiotic use (especially broad-spectrum agents such as clindamycin, cephalosporins, fluoroquinolones, and penicillins) disrupts the normal gut microbiota.
• This allows overgrowth of C. difficile and production of toxins A and B, which lead to colonic mucosal damage, inflammation, and diarrhoea.
• C. difficile spores are highly resistant to standard disinfectants and can persist in the environment, facilitating transmission.

Symptoms

• Diarrhoea: typically watery and frequent (≥3 loose stools in 24 hours).
• Abdominal pain or cramping.
• Fever.
• Nausea and loss of appetite.
• Malaise or generalised fatigue.

Signs

• Abdominal tenderness, particularly in the lower quadrants.
• Signs of dehydration: tachycardia, hypotension, dry mucous membranes.
• Severe disease:
  • Toxic megacolon
  • Complete ileus
  • Peritonitis or abdominal rigidity

Diagnosis

• Stool testing for C. difficile toxin is required for confirmation.
  • Only test patients with unexplained diarrhoea (≥3 loose stools in 24 hours).
• Blood tests:
  • Raised white cell count (WCC)
  • Elevated CRP
  • Acute kidney injury may be present in severe disease
• Severity assessment (UKHSA / Public Health England criteria):
  • Mild:
    • Normal WCC
    • <3 stools/day
  • Moderate:
    • WCC <15 × 10⁹/L
    • 3–5 loose stools/day
  • Severe:
    • WCC >15 × 10⁹/L
    • Temperature >38.5°C
    • Serum creatinine >50% above baseline
    • Clinical or radiological evidence of severe colitis
  • Life-threatening:
    • Hypotension
    • Complete ileus
    • Toxic megacolon
    • CT evidence of severe disease

Complications

• Severe dehydration
• Electrolyte abnormalities (e.g. hypokalaemia)
• Toxic megacolon
• Bowel perforation
• Pseudomembranous colitis
• Sepsis and multiorgan failure
• Death, particularly in elderly or frail patients

Management

Supportive Measures

• Fluid resuscitation
• Electrolyte replacement
• Stop the inciting antibiotic if possible

Medical Treatment

First Episode:

• First-line: Oral vancomycin 125 mg four times daily for 10 days
• Alternative: Oral fidaxomicin 200 mg twice daily for 10 days
• Severe infection: Consider oral vancomycin ± IV metronidazole 500 mg TDS

Recurrent CDI:

• Within 12 weeks: Oral fidaxomicin
• After 12 weeks: Vancomycin or fidaxomicin
• Multiple recurrences (≥2 episodes): Consider faecal microbiota transplant (FMT)

Life-Threatening CDI:

• Oral vancomycin 500 mg QDS
• IV metronidazole 500 mg TDS
• Surgical review (colectomy or diverting loop ileostomy may be indicated)
• ICU-level care if needed

Other Therapies

• Bezlotoxumab (monoclonal antibody targeting toxin B):
  • May reduce recurrence in high-risk patients
  • Not currently cost-effective for routine NHS use

Prevention

• Hand hygiene:

  • Use soap and water (alcohol gel is ineffective against spores)

• Infection control:

  • Single-room isolation
  • Personal protective equipment (PPE): gloves and apron
  • Environmental cleaning using chlorine-based disinfectants

• Antimicrobial stewardship:

  • Avoid unnecessary antibiotic use
  • Use narrow-spectrum agents where appropriate