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Clostridium difficile in adults: Epidemiology, microbiology, and pathophysiology

J Thomas Lamont, MD
Section Editor
Stephen B Calderwood, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Clostridium difficile is the causative organism of antibiotic-associated colitis. Colonization of the intestinal tract occurs via the fecal-oral route and is facilitated by disruption of normal intestinal flora due to antimicrobial therapy. The organism is capable of elaborating exotoxins that bind to receptors on intestinal epithelial cells, leading to inflammation and diarrhea (figure 1). (See "Clostridium difficile infection in adults: Clinical manifestations and diagnosis".)

Our understanding of C. difficile microbiology and epidemiology is changing rapidly. Issues related to C. difficile microbiology and epidemiology will be reviewed here. Clinical manifestations, diagnosis, and prevention and treatment of C. difficile are discussed separately. (See "Clostridium difficile infection in adults: Clinical manifestations and diagnosis" and "Clostridium difficile infection: Prevention and control" and "Clostridium difficile in adults: Treatment".)


Overview — Antibiotic-associated diarrhea and colitis were well established soon after widespread use of antibiotics [1]. In 1978, C. difficile was identified as the causative pathogen in the majority of cases, and the earliest cases of C. difficile were attributed largely to clindamycin [1,2]. Increasing use of penicillins and cephalosporins subsequently led to the implication of these antibiotic classes, although clindamycin remains an important culprit. Between 1989 and 1992, a strain of C. difficile highly resistant to clindamycin (the "J strain") was implicated in large outbreaks of diarrhea in four hospitals in the United States [3]. The use of clindamycin is a specific risk factor for this strain, and colonization with the clindamycin-resistant strain increases the risk for developing C. difficile–associated diarrhea (CDAD).

From 2003 to 2006, C. difficile infections were observed to be more frequent, severe, refractory to standard therapy, and likely to relapse than previously described [1]. These observations have occurred throughout North America and Europe and have been attributed to a new strain designated BI, NAP1, or ribotype 027 (these designations are based on different methods for strain typing and all refer to the same strain, known as strain NAP1/BI/027). This strain appears to be more virulent than other strains [4], which may be attributable to increased toxin production compared with conventional strains. Fluoroquinolone use has strongly correlated with the emergence of this strain [5], and acquisition of fluoroquinolone resistance by outbreak strains appears to have contributed to the increasing frequency of CDAD outbreaks [6]. (See 'Hypervirulent strain: NAP1/BI/027' below.)

In Quebec, Canada, an increase in the frequency and severity of CDAD was observed in the early 2000s [7,8]. A retrospective review of 1771 cases from this region demonstrated that, in 2003, the incidence of CDAD per 100,000 had increased fourfold since 1991; the incidence had risen 10-fold for individuals over 65 years of age [8]. Among hospitalized patients, the incidence increased from 3 to 12 per 1000 persons (1991 to 2002) to 25 to 43 per 1000 persons (2003 to 2004). These cases were more serious and refractory to therapy, with significant rates of toxic megacolon and disease requiring colectomy. Ten percent of cases required admission to an intensive care, and 2.5 percent underwent an emergency colectomy; the mortality was 16 percent [9].

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Literature review current through: Nov 2017. | This topic last updated: Dec 04, 2017.
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