Lecture Notes: Clostridium difficile Infection in Adults

Introduction

• Presented by Dr. Fer.
• Formerly known as Clostridium difficile, renamed in 2018.

Characteristics of Clostridium difficile

• Gram-positive anaerobe
  • Spore-forming: Survive aerobic conditions, alcohol ineffective, wash hands with soap.
  • Toxigenic strains: Produce toxins, specifically toxin A and B.

Significance of Infection

• High healthcare costs, 5% infection mortality, 15-20% all-cause mortality.
• CDC classified as an urgent threat.
• Despite reduced rates due to antimicrobial stewardship, >200,000 cases annually.

Pathophysiology

• Requires acquisition of C. difficile and gut microbiota disruption.
• Toxins disrupt GI tract epithelial cells, leading to severe immune responses.
• Manifestations: Diarrhea to toxic megacolon and death.

Acquisition

• Initial exposure in healthcare settings.
• Non-toxigenic variants: Asymptomatic colonization.
• Toxigenic variants:
  • Asymptomatic if immune system neutralizes toxins.
  • Symptomatic if immune response fails.

Guidelines & Treatment Options

• Guidelines: IDSA (2017 & 2021 updates), ACG (2021), AGA (2020).

Antibiotics for CDI

• Metronidazole: Disrupts DNA, 80% oral bioavailability, metallic taste.
• Vancomycin: Oral and IV options, low absorption, high fecal concentrations.
• Fidaxomicin: Oral, non-absorbed, reduces recurrence.
• Bezlotoxumab: Monoclonal antibody, reduces recurrence, caution in CHF.

Risks and Recurrent Infection

• Risk Factors: Antibiotic use, age >65, healthcare exposure, other comorbidities.

Clinical Presentation

• Ranges from asymptomatic to severe symptoms like diarrhea, fever, etc.
• Complications: Pseudomembranous colitis, shock, death.

Diagnostic Testing

• Preferred candidates: ≥3 unformed stools in 24 hours.
• Tests:
  • Nucleic Acid Amplification Test (NAAT): Sensitive, specific.
  • Stool Toxin Enzyme Immunoassay.
  • GDH Test: Detects C. difficile antigen.

Treatment Recommendations

• Initial Episode

  • Non-severe: Fidaxomicin preferred, Vancomycin alternative.
  • Severe: Avoid Metronidazole, same recommendations.
  • Fulminant: High-dose Vancomycin + IV Metronidazole.

• Recurrent Infection

  • First recurrence: Fidaxomicin or extended-pulse dosing.
  • Second or more recurrences: Consider fecal microbiota transplantation.
  • Additional options: Bezlotoxumab adjunctive therapy.

Prevention

• Minimize antibiotic use, restrict high-risk antibiotics.
• Probiotics not recommended for prevention.

Conclusion

• Comprehensive overview of C. difficile infection causes, treatments, and preventative measures.