Clostridium Difficile Infection

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  • A gram-positive, spore-forming anaerobic bacillus that releases toxins to produce clinical disease
  • Infection caused by Clostridium difficile is frequently associated with antibiotic use, hospitalization, residence at long-term care facilities, and age.
  • Severity of infection can range from diarrhea to pancolitis, perforation, and death.
  • System(s) affected: gastrointestinal
  • Synonyms(s): C. difficile–associated disease or diarrhea (CDAD); C. difficile infection; C. difficile colitis; C. diff


  • C. difficile is a common hospital-acquired infection. The incidence is rising (1).
  • There are ~15 new cases per 1,000 clinical discharges; higher with increased age (2)
  • Rates of complications are also increasing (1).

  • C. difficile causes ~25% of all cases of antibiotic-associated diarrhea.
  • Prevalence of community-acquired C. difficile infection is increasing. Up to 40% of patients require hospitalization (2).
  • C. difficile is a commensurate organism in 2–5% of the adult U.S. population.

Etiology and Pathophysiology

  • C. difficile is an anaerobic toxin-producing, gram-positive bacillus bacteria existing in vegetative and spore forms.
  • 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 (2).
  • 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 produces a much more virulent form of disease. It is associated with higher rates of colectomy and death.

No known genetic factors

Risk Factors

  • Host risk factors
    • Age >65 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) increases risk for C. difficile infection.
    • Commonly implicated antibiotics: ampicillin, amoxicillin, clindamycin (most common), cephalosporins, and fluoroquinolones
    • Chronic acid suppression may allow more bacteria to reach the colon (2).
  • Recurrence from prior infection
    • Recurrence rates are ~20%; recurrence more likely with each additional episode (2)
  • Can colonize ileum in patients with prior colectomy
  • 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).

Geriatric Considerations
C. difficile is the most common cause of acute diarrheal illness in long-term care facilities. Elderly patients often have multiple risk factors (comorbid disease, antibiotic exposure, medication use).

Pediatric Considerations
  • Neonates have a higher rate of C. difficile colonization (25–80%) but are generally less symptomatic than adults (possibly due to immature toxin receptors).
  • Frequently serve as carrier for infection in adults

General Prevention

  • Antibiotic stewardship program decreases the incidence of C. difficile infection.
  • 2010 Society for Healthcare Epidemiology of America (SHEA)/Infectious Diseases Society of America (IDSA) guidelines for prevention (3):
    • 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, including the use of nondisposable rectal thermometers.
    • Antimicrobial restrictions
      • Minimize the frequency and duration of antibiotic therapy. Use particular care when prescribing commonly implicated antibiotics.

Commonly Associated Conditions

Pseudomembranous colitis, toxic megacolon, sepsis, colonic perforation

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