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Pseudomembranous colitis (PMC) was first described in 1893 by Finney as a post-operative complication of gastrojejunostomy for an obstructive peptic ulcer (1). It is a clinicopathological diagnosis based on diarrhea and exudative raised plaques with skipped areas of hyperemic colonic mucosa (2). These plaques may enlarge and coalesce over large segments of intestine. The primary cause in the last thirty years has been antibiotics, while other causes have included surgery, uremia, heavy metal poisoning and ischemic heart disease (3,4). Antibiotic-associated PMC is caused by toxins produced by the bacterium Clostridium difficile. The use of antibiotics alters the normal bacterial flora to allow C. difficile to proliferate. PMC usually becomes symptomatic 4-10 days after the initiation of antibiotic therapy but approximately 15-25 % of patients develop symptoms only after discontinuation of therapy, usually within 4-6 weeks (4). Some patients may have resolution of PMC without stopping the causative drug, while others have diarrhea continuing up to 8 weeks. Although stopping the offending agent in some patients prevents further diarrhea, many cases will need oral vancomycin and metronidazole. The relapse rate is around 9 % and for these resistant cases, rifampin is suggested (2). Complications of PMC include toxic megacolon and perforation and, for severely ill patients, the mortality rate is as high as 30 % (2). Chemotherapeutic agents have also been implicated as causative factors in the pathogenesis of PMC, with 15 reported cases of chemotherapy-associated PMC unrelated to antibiotic use. Responsible agents have included cytarabine (5), methotrexate (6), 5-fluorouracil (7,8), ChlVPP (9), CVB (10), CMF (11) and CAP (12). Cases of PMC in patients receiving both chemotherapy and antibiotics have also previously been reported in ovarian cancer patients (12) and in one series of leukemic patients, all five of whom died from secondary complications of PMC (13). In recent years, it has been shown that adjuvant chemotherapy is beneficial in prolonging disease-free survival in several forms of cancer, most notably colon and breast (14,15). As these patients are essentially asymptomatic from their disease, it is important that the risks of such potentially useful therapy be kept to a minimum. However, it is likely that with the increasing utilization of chemotherapy, the incidence of complications, sometimes severe and tragic, will also rise, forcing a greater care in its administration and perhaps a more informed and critical appraisal of its advantages. With this in mind, the current authors describe a fatal case of severe PMC with features of toxic megacolon related to both previous antibiotic therapy and adjuvant chemotherapy.

Sequential use of Antibiotics and Adjuvant Chemotherapy Leading to a Fatal Pseudomembranous Colitis