INTRODUCTION AND EPIDEMIOLOGY
Key Clinical Questions
Which factors are associated with an increased risk of primary or recurrent Clostridium difficile–associated disease (CDAD)?
What factors affect the accuracy of diagnostic testing of CDAD?
What are the most common complications of CDAD?
What therapies are most efficacious for primary, recurrent, or refractory CDAD?
What system improvements can reduce the incidence of CDAD?
Clostridium difficile was first described in 1935 by pediatricians studying the acquisition of bowel flora in newborns and was termed “difficult” because of its resistance to growth on conventional media. It was not until 1978 that it was found to be associated with toxins in the stools of patients with colitis. Clostridium difficile–associated disease (CDAD) has now become a major nosocomial problem, affecting three million inpatients yearly in the United States. Acquisition of C. difficile occurs in up to 30% of hospitalized patients, although only 30% to 60% have symptoms. Patients with symptomatic disease stay an average of 3.6 days longer in hospital than expected, at a cost of over $3.2 billion annually in the United States.
Normal gut flora confers resistance to C. difficile colonization; only 1% to 4% of healthy adults carry C. difficile in their bowel flora. Loss of normal colonic flora, usually from antibiotics, allows C. difficile proliferation (clindamycin, cephalosporins, and fluoroquinolones are common offenders). C. difficile colitis is also associated with other events that disturb gut flora or host immunity, such as bowel preparations, cytotoxic agents, and colonic inflammation due to inflammatory bowel disease.
CDAD was first described in frail or elderly hospitalized patients after antibiotic exposure, but it is now occurring in younger, healthy individuals with no apparent exposure to health care environments or antibiotics. Up to ~20% of CDAD cases are now community-acquired. C. difficile and its spore form are easily transmitted from person-to-person or by contact with objects in the hospital environment, such as stethoscopes, clothing, and toilets. The spore form is ubiquitous in the hospital environment, is resistant to alcohol-based treatment and other disinfectants, and can survive for months. Even after routine cleaning, 10% to 50% of room surfaces still contain spores.
C. difficile is an anaerobic spore-forming bacterium that produces two exotoxins (A and B) that adhere to intestinal epithelial cells, causing cell death. These toxins are transcribed from a locus composed of five genes (two toxin genes and three regulatory genes). The epidemic strain of C. difficile (BI/NAP1/027) has several factors that increase its virulence. A mutation in one of the regulatory genes results in a massive increase in toxin production. This strain also shows high-level fluoroquinolone resistance, giving it a competitive advantage in environments where fluoroquinolone use is widespread. This strain also produces an additional toxin (binary toxin), which is of uncertain clinical significance.
Patient risk of acquiring CDAD and severity of clinical illness are variable (...