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Clostridioides difficile Infection

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Overview

Clostridioides difficile (C. difficile) is a Gram-positive anaerobic rod spread by bacterial spores found in faeces. It is known for causing inflammation of the colon. Surfaces may be contaminated with spores and spread via the hands of healthcare workers.

A key risk factor is the use of broad-spectrum systemic antibiotics, which can kill competing bacteria that exist as part of the intestine’s flora, allowing C. difficile to colonise the gut. Subsequent inflammation (colitis) can occur due to the release of toxins. Severe colitis secondary to C. difficile infection can lead to the formation of pseudomembranes, which are collections of inflammatory and necrotic cells. This is known as pseudomembranous colitis.

Risk Factors

  • Antibiotic use:
    • Common culprits are clindamycin, cephalosporins, and tetracycline
  • Increased age
  • Exposure to an infected individual
  • Use of proton pump inhibitors
  • Inflammatory bowel disease (IBD)
  • Immunosuppression

Presentation

Patients may be asymptomatic, have mild disease, pseudomembranous colitis, or fulminant colitis. Features generally emerge 5-10 days after antibiotic exposure:

Investigations

  • Full blood count:
    • White cell count (WCC) is raised in around 80% of patients
  • Stool C. difficile toxin testing:
    • May be done using toxin enzyme immunoassays (EIAs), toxin gene nucleic acid amplification tests (NAAT), or toxin polymerase chain reaction (PCR)
    • The presence of toxins suggests infection. C. difficile antigens only show its presence and do not confirm infection, as it may be present without causing disease

Severity Stratification

Patients may be categorised based on the presence of certain features:

  • Mild:
    • WCC normal
    • <3 loose stools
  • Moderate:
    • Increased WCC but <15 x 109/L
    • Typically associated with 3-5 loose stools
  • Severe:
    • Increased WCC >15 x 109/L
    • Increased serum creatinine (>50% of baseline)
    • Temperature >38.5°C
    • Abdominal or radiological evidence of severe colitis
  • Life-threatening:

Management

Acute C. difficile infection – patient stable

Initially review current antibiotic therapy and stop them if possible. For stable patients with a first episode of C. difficile:

  • 1st-line: oral vancomycin
  • 2nd-line: oral fidaxomicin
  • 3rd-line: oral vancomycin with or without IV metronidazole
    • Vancomycin is poorly absorbed from the gut, making it good for use in C. difficile as it remains there

Acute life-threatening C. difficile infection

  • 1st-line: oral vancomycin + IV metronidazole
  • Seek urgent specialist advice as surgery may be necessary

Recurrent C. difficile infection

  • ≤12 weeks of symptom resolution: oral fidaxomicin
  • ≥12 weeks following symptom resolution: oral vancomycin or fidaxomicin
  • Faecal microbiota transplants may be considered in adults who have had ≥2 episodes

Patient Advice

  • Drink enough fluids to avoid dehydration
  • Take measures to prevent infection spread (e.g. effective handwashing etc.)
  • Seek medical help if symptoms worsen
  • Prebiotics or probiotics do not have much evidence suggesting their efficacy in preventing or treating C. difficile infection

Complications

  • Ileus:
    • Defined as slowing GI motility not associated with mechanical obstruction
    • Usually presents with worsening nausea and vomiting
    • Occurs due to pseudomembrane formation and bowel wall thickening
  • Perforation:
    • Usually presents with acute severe abdominal pain, rebound tenderness, fever, tachycardia, and hypotension
  • Toxic megacolon:
    • Describes dilation of the colon
    • Usually presents with abdominal pain and distension, tachycardia, and hypotension
    • Thought to be due to inflammatory damage to the muscular tissue and neurones

Prognosis

  • Most patients respond to initial treatment and symptoms resolve within 4-6 days
  • Thorough handwashing is effective at preventing its spread. Alcohol gels do not kill spores.

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