Antibiotic-Associated Pseudomembranous Colitis

C. difficile was originally described in 1935 but was of minimal clinical interest until recently, when studies showed it to be the cause of antibiotic-associated PMC. Intestinal complications caused by C. difficile appear almost exclusively in conjunction with exposure to antibiotics. Evidence that supports the etiologic role of this organism in antibiotic-associated PMC comes from both bacteriological studies and tissue culture assays. Tissue culture assays have been used to demonstrate that the stool supernate from nearly all patients with anatomically confirmed PMC contains a cytotoxin that is neutralized with Clostridium sordellii antitoxin. The cytotoxin has rarely been found in persons without gastro-intestinal complications related to antibiotic usage. Cultures of stool from patients with anti-biotic-associated PMC usually yield C. difficile, which is encountered only infrequently in the fecal flora of healthy persons. Strains of C. difficile have been shown to cause a similar disease in experimental animals administered antibiotics or intracecal injections of broth cultures of C. difficile. According to the antitoxin neutralization tests and biochemical purification studies done to date, C. difficile is the only organism that produces a cytotoxin similar or identical to the cytotoxin encountered in stools of patients with PMC. The toxin is a high-molecular-weight protein that appears to cause changes in the permeability of cells in tissue culture. However, the mechanism of its action on intestinal mucosa and the cause of its production with antibiotic exposure in clinical settings have not been well defined.