Causes of Clostridioides difficile Infection
Clostridioides difficile infection (CDI) is primarily caused by disruption of the normal gut microbiota (usually due to antibiotic use) combined with exposure to toxigenic C. difficile spores, which allows the organism to proliferate and produce toxins that damage the colonic mucosa. 1
Primary Causative Factors
Disruption of Normal Gut Microbiota
- Antibiotic exposure: The most important risk factor for CDI 1
- Particularly high-risk antibiotics:
- Clindamycin (highest risk)
- Fluoroquinolones
- Cephalosporins
- Beta-lactam/beta-lactamase inhibitor combinations 1
- Particularly high-risk antibiotics:
- Mechanism: Antibiotics alter the normal intestinal microbiota, creating an ecological niche that allows C. difficile to proliferate 1
Exposure to C. difficile
- Healthcare-associated transmission:
- Hands of healthcare personnel transiently contaminated with C. difficile spores
- Environmental contamination in healthcare settings
- Shared high-risk fomites (electronic rectal thermometers, inadequately cleaned commodes or bedpans) 1
- Community-associated transmission:
Pathogenesis
Toxin Production
- Key to pathogenesis: Non-toxigenic strains of C. difficile do not cause diarrhea 1
- Primary toxins:
- Mechanism of damage:
- Toxins disrupt epithelial integrity via microtubules and cell-cell tight junctions
- Cause cytokine release (e.g., IL-8)
- Promote inflammatory infiltrate in colonic mucosa
- Create fluid shifts leading to diarrhea
- Cause epithelial necrosis 1
Risk Factors
Patient-Specific Factors
- Age: Older age increases risk 1
- Healthcare exposure:
- Recent hospitalization
- Longer hospitalization duration 1
- Medication use:
- Multiple antibiotics or longer duration of antibiotic use
- Proton pump inhibitors 1
- Medical conditions:
- Chronic kidney disease
- Inflammatory bowel disease
- Immunocompromised status (HIV/AIDS, cancer patients, solid organ transplant recipients) 1
- Medical interventions:
- Chemotherapy
- Feeding tubes 1
Environmental Factors
- Room occupancy: Occupying a room where a prior occupant had CDI (accounts for ~10% of cases) 1
- Ward-level antibiotic use: High antibiotic use in a hospital ward increases risk even for patients not directly receiving antibiotics 1
Special Populations
Children
- Asymptomatic colonization: Common in infants and young children
- Up to 40-73% in infants under 6 months
- Decreases with age, reaching adult levels (0-3%) by age 3 years 1
- Testing recommendations: C. difficile should not be routinely tested in children under 2 years with diarrhea 1
Immunocompromised Patients
- Higher risk due to:
- Ongoing immunosuppression
- Frequent antibiotic use
- Chemotherapy
- Low CD4 counts in HIV/AIDS patients 1
Prevention Strategies
- Antibiotic stewardship: Critical to decrease CDI rates 3
- Hand hygiene:
- Either soap and water or alcohol-based products in routine settings
- Soap and water preferred during outbreaks 3
- Contact precautions: For patients with confirmed CDI 4
- Environmental cleaning: Proper disinfection of healthcare environments 1
Important Clinical Considerations
- Asymptomatic colonization is common (up to 8.1% of patients upon hospital admission) 1
- Testing should only be performed on symptomatic patients with ≥3 unformed stools in 24 hours 1, 4
- "Test of cure" is not recommended as >60% of patients may remain C. difficile positive even after successful treatment 4
- The incubation period between colonization and infection may be longer than previously thought (>1 week in some cases) 1
Understanding these causative factors is essential for implementing effective prevention and treatment strategies for C. difficile infection.