Chapter 123. Clostridium difficile–Associated Disease, Including Pseudomembranous Colitis (Part 1) Harrison's Internal Medicine Chapter 123. Clostridium difficile– Associated Disease, Including Pseudomembranous Colitis Etiology and Epidemiology C. difficile is an obligately anaerobic, gram-positive, spore-forming bacillus whose spores are found widely in nature, particularly in the environment of hospitals and chronic-care facilities. CDAD occurs most frequently in hospitals and nursing homes where the level of antimicrobial use is high and the environment is contaminated by C. difficile spores. Clindamycin, ampicillin, and cephalosporins were the first antibiotics associated with CDAD. The second- and third-generation cephalosporins, particularly cefotaxime, ceftriaxone, cefuroxime, and ceftazidime, are agents frequently responsible.