Metronidazole may inhibit intestinal colonization with Clostridium difficile

Dis Colon Rectum. 1998 Apr;41(4):464-7. doi: 10.1007/BF02235760.

Abstract

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 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 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 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.

Conclusions: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Clostridioides difficile / drug effects*
  • Colorectal Surgery*
  • Double-Blind Method
  • Drug Therapy, Combination / therapeutic use*
  • Enterocolitis, Pseudomembranous / prevention & control*
  • Erythromycin / therapeutic use
  • Female
  • Humans
  • Intestines / drug effects
  • Intestines / microbiology*
  • Male
  • Metronidazole / therapeutic use*
  • Middle Aged
  • Neomycin / therapeutic use
  • Preoperative Care*
  • Prospective Studies

Substances

  • Anti-Bacterial Agents
  • Metronidazole
  • Erythromycin
  • Neomycin