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Chapter 204 Clostridium difficile Infection
Ethan A. Mezoff, Mitchell B. Cohen
Clostridium difficile infection (CDI), also known as pseudomembranous colitis, antibiotic-associated diarrhea, or C. difficile–associated diarrhea, refers to gastrointestinal colonization with C. difficile resulting in a diarrheal illness. Reports have indicated an increase in both incidence and severity of CDI.
C. difficile is a gram-positive, anaerobic bacillus capable of forming a spore that is resistant to killing by alcohol. Organisms causing symptomatic disease produce one or both of the following: toxin A and toxin B. These toxins affect intracellular signaling pathways, resulting in inflammation and cell death. The cytotoxic Binary toxin, an AB toxin, is not present in the majority of strains but has been detected in recent epidemic strains.
The incidence of CDI increased 48%, from 2.5 to 3.7 cases/1000 pediatric admissions, between 2001 and 2006. The age group most affected was 1 to 5 yr old children, with an 85% increase in CDI rates. Concurrent with this rise in incidence, disease severity has also increased, as evidenced by changes in colectomy and mortality rates in adults (thus far increases in colectomy and mortality rates have not been observed in the pediatric population).
A hypervirulent strain, denoted NAP1/BI/027, has acquired fluoroquinolone resistance, leading to outbreaks throughout North American and European hospitals. This strain produces binary toxin and exhibits 16- and 23-fold increases in the production of toxins A and B production, respectively. The specific role of this hypervirulent strain in the changing epidemiology of CDI is not yet completely understood.
Asymptomatic carriage occurs with non–toxin-producing strains as well as in neonates, who may lack the toxin receptor. Carrier frequency rates of 50% may occur in children younger than 1 yr but decline to 3% by age 2. Carriers can infect other susceptible individuals.
Risk factors for CDI include use of broad-spectrum antibiotics, hospitalization, gastrointestinal surgery, inflammatory bowel disease, chemotherapy, enteral feeding, proton pump–inhibiting agents, and chronic illness. Once thought to be exclusively a nosocomial, iatrogenic disease, CDI is increasingly recognized in the community. Half of all community-acquired cases occur in the pediatric population, and 35% of these infections occur with no history of antibiotic exposure.
Disease is caused by gastrointestinal infection with a toxin-producing strain. Any process that disrupts normal flora, impairs the normal gastrointestinal immune response (e.g., inflammatory bowel disease [IBD]), or inhibits intestinal motility may lead to infection. Normal bowel flora appears to be protective, conferring “colonization resistance.”
By affecting intracellular signaling pathways and cytoskeletal organization, toxins induce an inflammatory response and cell death, leading to diarrhea and pseudomembrane formation. Antibodies against toxin A have been shown to confer protection from symptomatic disease, and failure of antibody production has been shown to occur in patients with recurrent disease.
Infection with toxin-producing strains of C. difficile leads to a spectrum of disease ranging from mild, self-limited diarrhea to explosive, watery diarrhea with occult blood or mucous, to pseudomembranous colitis, and even death. Pseudomembranous colitis describes a bloody diarrhea with accompanying fever, abdominal pain/cramps, nausea, and vomiting. Rarely, small gut involvement, bacteremia, abscess formation, toxic megacolon, and even death can occur.
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