Metronidazole may inhibit intestinal colonization with Clostridium difficile

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 preoperative bowel preparation, prevents or decreases incidence of antibiotic-associated colitis after elective colonic and rectal procedures.

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 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.

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 for C. difficile. Relative risk of colonization with C. 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 in C. difficile colonization rates with respect to age, length of stay, or gender.

This study suggests that there may be a clinical association between use of metronidazole preoperatively and inhibition of intestinal colonization by C. difficile in this patient population undergoing colonic and rectal surgery.