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.