Clostridium difficile Infection


Clostridium difficile infection ( CDI ), also known as pseudomembranous colitis or C. difficile –associated diarrhea, refers to gastrointestinal (GI) colonization with C. difficile resulting in a diarrheal illness. It is a common cause of antibiotic-associated diarrhea and the most common cause of healthcare-associated infections in the United States, accounting for 12% of these infections. An increase in inpatient and outpatient acquisition of CDI has been observed, and new risk factors have been identified, fueling the development of new therapeutic options.

Etiology

Clostridium difficile (which has been renamed Clostridioides difficile ) is a gram-positive, spore-forming, anaerobic bacillus that is resistant to killing by alcohol. It is acquired from the environment or by the fecal-oral route. Organisms causing symptomatic intestinal disease produce 1 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 epidemic strains.

Epidemiology

Once thought to be an infrequent infection of chronically ill and hospitalized patients, the incidence of CDI is increasing in pediatric patients, and the setting of acquisition is changing. The incidence in pediatric patients increased 48%, from 2.5 to 3.7 cases per 1,000 admissions between 2001 and 2006. A population-based cohort study over a similar period found that 75% of cases were community acquired and 16% had no preceding hospitalization or antibiotic exposure. Similar 2011 CDC national data estimate3 cases of community-acquired CDI in children for every healthcare-acquired case. In addition to an overall increase in all strains, a hypervirulent strain , denoted NAP1/BI/027 (also called BI ), has emerged and is estimated to cause 10–20% of pediatric infections. This strain produces binary toxin and exhibits 16- and 23-fold increases in the production of toxins A and B, respectively. The specific role of this hypervirulent strain in the changing epidemiology of CDI is not completely understood.

Asymptomatic carriage occurs with potentially pathogenic strains and is common in neonates and infants ≤1 yr old. A carrier frequency rate of 50% may occur in children <1 yr old, but the rate declines by age 3 yr. Carriers can infect other susceptible individuals.

Risk factors for CDI include the use of broad-spectrum antibiotics, hospitalization (particularly if the prior room occupant was infected), GI surgery, inflammatory bowel disease (IBD), chemotherapy, enteral tube feeding, proton pump inhibitor (PPI) or H 2 -receptor antagonist use, and chronic illness.

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