Clostridium Difficile Infection



  • A gram-positive, spore-forming anaerobic bacillus that releases toxins to produce clinical disease
  • Associated with antibiotic use, hospitalization, residence at long-term care facilities, and age
  • Severity of infection ranges from asymptomatic carrier to diarrhea, colitis, sepsis, perforation, and death.
  • Transmission of spores is typically person-to-person via the fecal-oral route but may also occur through exposure to contaminated surfaces or equipment. Clostridioides difficile spores can survive on dry surfaces for up to 5 months.
  • System(s) affected: gastrointestinal
  • Synonym(s): C. difficile infection, C. difficileassociated disease or diarrhea (CDAD); C. difficile infection; C. difficile colitis; C. diff



  • Colonization with C. difficile found in:
    • 2–10% of community, 3–18% of inpatients, 4–20% of long-term residents (1)
  • Global estimated incidence of C. difficile infection 50/100,000/year; hospitalization rates are increasing (2).
  • National incidence of health care–associated C. difficile infection 73/100,000 persons (3)
  • National incidence of community acquired C. difficile infection 52/100,000 persons
  • 14 cases per 1,000 adults in 2015 (4)


  • Prevalence increasing in the United States in both health care settings and the community
  • C. difficile accounted for 12% of health care–associated infections in 2010.
  • >2 million cases of C. difficileassociated disease in U.S. hospitals from 1993 to 2005

Etiology and Pathophysiology

  • C. difficile is an anaerobic toxin-producing, gram-positive bacillus bacteria existing in vegetative and spore forms.
  • ~One week incubation period
  • Spores can survive for months in harsh conditions and outside of the body.
  • Spread by fecal-oral contact; acid-resistant spores pass through stomach to reside mostly in the colon.
  • Colonic colonization causes disruptions in barrier functions of the normal microbiome.
  • C. difficile is noninvasive. Toxins mediate disease:
    • Toxins A (enterotoxin) and B (cytotoxin) attract neutrophils and monocytes, degrading colonic epithelial cells and causing clinical disease.
  • The hypervirulent strain BI/NAP1/027 of C. difficile is associated with higher rates of colectomy and death.

No known genetic factors

Risk Factors

  • Host risk factors
    • Age >70 years; hospitalization or long-term health care facility
    • Comorbidities, including inflammatory bowel disease, immunosuppression, chronic liver disease, and end-stage renal disease
    • Enteral feeding; previous C. difficile infection
  • Factors that disrupt normal colonic microbiota:
    • Exposure to antibiotics (including perioperative prophylaxis)
    • Commonly implicated antibiotics: ampicillin, amoxicillin, clindamycin (most common), cephalosporins, and fluoroquinolones
    • Chronic acid suppression
  • Recurrence from prior infection
    • Recurrence rates are ~25%; recurrence more likely with each additional episode
  • Community-acquired C. difficile infections (no overnight admission in >12 weeks) are more frequent in patients without other risk factors (younger, no recent antibiotic exposure).
  • Risk increases with length of hospital stay, duration of antibiotics exposure, and number of antibiotics used (5).

Geriatric Considerations
C. difficile is the most common cause of acute diarrheal illness in long-term care facilities.

Pediatric Considerations

  • Neonates have a higher rate of C. difficile colonization (25–80%) but are generally less symptomatic than adults.
  • Frequently serve as carrier for infection in adults

General Prevention

  • Antibiotic stewardship programs decrease the incidence of C. difficile infection.
  • Society for Healthcare Epidemiology of America (SHEA)/Infectious Diseases Society of America (IDSA) guidelines for prevention:
    • For health care workers, patients, and visitors:
      • Contact precautions, including gloves and gowns, on entry to room; alcohol-based hand sanitizers are not effective. Hand washing with soap and water before and after patient interaction is recommended.
      • Accommodate patients with C. difficile infection in private rooms, if possible.
    • Environmental cleaning and disinfection
      • Disinfect with hypochlorite or other spore-killing solution.
      • Identify and reduce environmental sources of C. difficile.
    • Antimicrobial restrictions
      • Minimize the frequency and duration of antibiotic therapy.

Commonly Associated Conditions

Pseudomembranous colitis, toxic megacolon, sepsis, colonic perforation

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