Metronidazole may inhibit intestinal colonization withClostridium difficile

Abstract

PURPOSE: Antibiotics suppress normal gut flora, allowing overgrowth of acquired or nativeClostridium 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 preoperative 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 polyethylene 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 neomycin and metronidazole. Both groups received one preoperative and three postoperative doses of intravenous cefotetan (2 g/dose). Both groups had stool samples tested forC. difficile toxin in the preoperative and postoperative periods by enzyme-linked immunoabsorbent assay or by tissue culture cytotoxicity. Patients with preoperative stool studies positive forC. 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 patients in Group 1 (neomycin and erythromycin) and one patient in Group 2 (neomycin and metronidazole) had positive stool studies forC. difficile. Relative risk of colonization withC. difficile in Group 1 was 4.76 times that in Group 2 (95 percent confidence interval, 0.581, 39). This difference was not statistically significant (P=0.202). There were no significant differences inC. difficile colonization 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 preoperatively and inhibition of intestinal colonization byC. difficile in this patient population undergoing colonic and rectal surgery.