TAILIEUCHUNG - Chapter 123. Clostridium difficile–Associated Disease, Including Pseudomembranous Colitis (Part 2)

Patients colonized with C. difficile were initially thought to be at high risk for CDAD. However, four prospective studies have shown that colonized patients actually have a decreased risk of subsequent CDAD. At least three events are proposed as essential for the development of CDAD (Fig. 123-2). Exposure to antimicrobial agents is the first event and establishes susceptibility to C. difficile infection. The second event is exposure to toxigenic C. difficile. Given that the majority of patients do not develop CDAD after the first two events, a third event is clearly essential for its occurrence. Candidate third events include. | Chapter 123. Clostridium difficile-Associated Disease Including Pseudomembranous Colitis Part 2 Patients colonized with C. difficile were initially thought to be at high risk for CDAD. However four prospective studies have shown that colonized patients actually have a decreased risk of subsequent CDAD. At least three events are proposed as essential for the development of CDAD Fig. 123-2 . Exposure to antimicrobial agents is the first event and establishes susceptibility to C. difficile infection. The second event is exposure to toxigenic C. difficile. Given that the majority of patients do not develop CDAD after the first two events a third event is clearly essential for its occurrence. Candidate third events include exposure to a C. difficile strain of particular virulence exposure to antimicrobial agents especially likely to cause CDAD and an inadequate host immune response. The host anamnestic serum IgG antibody response to toxin A of C. difficile is the most likely third event that determines which patients develop diarrhea and which patients remain asymptomatic. The majority of humans first develop antibody to C. difficile toxins when colonized asymptomatically during the first year of life. Infants are thought not to develop symptomatic CDAD because they lack suitable mucosal toxin receptors that develop later in life. In adulthood serum levels of IgG antibody to toxin A increase more in response to infection in individuals who become asymptomatic carriers than in those who develop CDAD. For persons who develop CDAD increasing levels of antitoxin A during treatment correlate with a lower risk of recurrence of CDAD. Figure 123-2 Pathogenesis model for hospital-acquired Clostridium difficile-associated diarrhea CDAD . At least three events are integral to C. difficile pathogenesis. Exposure to antibiotics establishes susceptibility to infection. Once susceptible the patient may acquire nontoxigenic nonpathogenic or toxigenic strains of C. difficile as a second

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