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CLOSTRIDIUM DIFFICILE

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Clostridium difficile is a spore-forming, obligate anaerobic, gram-positive bacillus that is spread via the fecal-oral route. The most common manifestations of C difficile–associated disease (CDAD) are mediated by toxins A and B produced by the organism.

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PATHOGENESIS AND EPIDEMIOLOGY

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Treatment with antibiotics and chemotherapeutic agents (eg, fluorouracil, methotrexate) that alter the natural gastrointestinal flora favor the emergence of C difficile. Risk factors for developing CDAD include recent gastrointestinal surgery, prolonged stays in healthcare facilities, immunocompromised patients, proton pump inhibitor therapy, repeated enemas, prolonged use of nasogastric tubes (or other gastrointestinal feeding devices), inflammatory bowel disease, cystic fibrosis, Hirschsprung disease, and a history of cancer. Breastfeeding, on the other hand, may offer some protective benefits. Studies report that 3% to 7% of children with C difficile develop a complication, such as hypotension, ileus, or toxic megacolon.

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CDAD results directly from toxin-mediated effects to the large intestine. The exact incubation period is unknown, but symptoms are known to develop up to 10 weeks after discontinuation of antibiotics. Infants and children are more likely than adults to carry C difficile asymptomatically in the gastrointestinal tract; it is estimated that 15% to 63% of neonates, up to 33% of infants and toddlers younger than 2 years of age, and up to 8.3% of children older than 2 years of age are asymptomatic carriers. It is postulated that infants do not manifest illness because they lack the necessary toxin-binding sites in their colon. In children who have diarrhea not caused by C difficile, many may still carry C difficile. Over the past decade, more severe, sometimes fatal infections have been seen with outbreaks of C difficile infection caused by a virulent strain (NAP-1/027) that appears to have increased production of toxins A and B, as well as binary toxin, and fluoroquinolone resistance.

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In 2011, the estimated incidence of C difficile infection in the United States in children < 18 years old was 24.2 cases per 100,000 population, with approximately two-thirds of cases being community-associated. With the rate of C difficile colonization or infection in hospitalized patients being 13 per 1000, CDAD is now the most common cause of healthcare-associated infection, with an estimated 453,000 incidents of CDAD, including 29,300 deaths, in the United States, resulting in an estimated cost of $5 billion in 2011.

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CLINICAL MANIFESTATIONS

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Colonization is defined as a patient who exhibits no clinical symptoms but tests positive for the C difficile organism and/or its toxin. Colonization is more common than symptomatic CDAD.

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The presentation of CDAD can range from mild diarrhea to life-threatening disease. Initial signs and symptoms of CDAD include watery diarrhea, fever, loss of appetite, nausea, and abdominal tenderness. Progressive signs and symptoms include bloody diarrhea, cramping, and flatulence. If pseudomembranous colitis is suspected, it requires a colonoscopy to confirm the diagnosis. More severe complications include toxic megacolon, perforation, and bacteremia with distant metastatic infection. Therefore, a high index of suspicion is critical, as ...

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