Metronidazole May Inhibit Intestinal Colonization with Clostridium difficile R. K. Cleary, M.D., R. Grossmann, M.D., F. B. Fernandez, M.D., T. S. Stull, M.D., J. J. Fowler, B.S.N., R.N., M. R. Waiters, M.S., R.N., R. M. Lampman, Ph.D. From the Department of Surgery, St. Joseph Mercy Hospilal, Ann Arbog Michigan PURPOSE: Antibiotics suppress normal gut flora, allowing overgrowth of acquired or native Clostridium difficile, with release of toxins that cause mucosal inflammation. Oral metronidazole is used to treat antibiotic-associated colitis (pseudomembranous colitis). This study was designed to determine whether oral metronidazole, as part of preoper- ative bowel preparation, prevents or decreases incidence of antibiotic-associated colitis after elective colonic and rectal procedures. METHODS: Eighty-two patients (40 men) were prospectively-, randomly assigned to receive one of two oral antibiotic regimens before colorectal surgery. All patients underwent mechanical bowel preparation with polyethyl- ene glycol-electrolyte lavage solution before administration of oral antibiotics. Group 1 (n = 42) patients received three doses (1 g/dose) of neomycin and erythromycin. Group 2 (n = 40) patients received three doses (1 g/dose) of neo- mycin and metronidazole. Both groups received one preop- erative and three postoperative doses of intravenous ce- fotetan (2 g/dose). Both groups had stool samples tested for C difficile toxin in the preoperative and postoperative periods by enzyme-linked immunoabsorbent assay or by tissue culture cytotoxicity. Patients with preoperative stool studies positive for C difficile were excluded from the study. RESULTS: Treatment groups were not different for age, gender, or surgical procedure. Mean age -+ 1 standard deviation was 67.6 + 13.6 (range, 34-94) years in Group 1 and 62.1 + 13.5 (range, 35-84) years in Group 2 (P = 0.069). Mean length of hospital stay + 1 standard deviation was 9.76 -+ 4.9 (range, 4-28) days for Group 1 and 8.05 -+ 2.6 (range, 3-14) days for Group 2 (P = 0.053). Five pa- tients in Group 1 (neomycin and erythromycin) and one patient in Group 2 (neomycin and metronidazole) had pos- itive stool studies for C, difficile. Relative risk of coloniza- tion with C. difficile in Group 1 was 4.76 times that in Group 2 (95 perceut confidence interval, 0.581, 39). This difference was not statistically significant (P = 0.202). There were no significant differences in C. difficile coloni- zation rates with respect to age, length of stay, or gender. CONCLUSIONS: This study- suggests that there may be a clinical association between use of metronidazole preoper- atively and inhibition of intestinal colonization by C. d/f~'- cile in this patient population undergoing colonic and rectal surgery. [Key" words: Antibiotic-associated colitis; Pseudomembranous colitis; C difficile colitis; Antibiotic- associated diarrhea] Cleary RK, Grossman R, Fernandez FB, Stull TS, Fowler JJ, Supported, in part, by the Department of Research at St. Joseph Mercy ttospital, Ann Arbor, Michigan. Poster presentation at the meeting of The American Society of CoIon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997. Address reprint requests to Dr. Cleary: St. Joseph Mercy Hospital, 5333 McAuley Drive, Suite 5115, A*m Arbor, Michigan 48106. Waiters MR, Lampman RIM. Metronidazole may inhibit in- testinal colonization with Clostridium difficile. Dis Colon Rectum 1998;41:464-467. A ntibiotic-associated colitis, first described by Finney in 1893,1 has become more prevalent with increasing use of antibiotics and antineoplastic drugs with antibiotic properties. Normal gut flora may prevent intestinal colonization by Clostridium diffi- cile, an organism whose toxin is thought to cause colitis. 1-3 Antibiotics may suppress normal gut flora, allowing overgrowth of C. difficite, with release of toxins that cause mucosal inflammation. 4-7 Of those patients contracting C. difficile-associated colitis, 90 percent have received antibiotic therapy, and almost 50 percent do so after surgical proceduresff The most frequent oral antibiotic combinations used in me- chanical bowel preparations before colonic and rectal surgical procedures are neomycin and erythromycin and neomycin and metronidazole. Intravenous cepha- losporin is often used in the perioperative period for wound prophylaxis. Bartlett et al. 5 demonstrated that pretreatment with "gas gangrene antitoxin" prevents a fatal form of antibiotic-associated colitis in hamsters. Because intravenous cephalosporins are considered a common cause of antibiotic-associated colitis 8 and be- cause metronidazole is commonly used to treat this disease, it would be important to know whether use of oral metronidazole as part of the preoperative prepara- tion would decrease the incidence of intestinal coloni- zation with C difficile after colonic and rectal surgical procedures. In this study, patients undergoing elective colonic and rectal surgery received either oral neomycin and eryth- romycin or oral neomycin and metronidazole as part of their preoperative bowel preparation. Incidence of in- testinal colonization with C. difficile was then compared in the two groups to see whether there is a protec~ve effect in those who receive metronidazole. PATIENTS AND METHODS This was a prospective double-blind study using simple randomization. It was approved by the Insti- 464