Rk. Cleary et al., METRONIDAZOLE MAY INHIBIT INTESTINAL COLONIZATION WITH CLOSTLIDIUM DIFFICILE, Diseases of the colon & rectum, 41(4), 1998, pp. 464-467
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 antib
iotic-associated colitis (pseudomembranous colitis). This study was de
signed to determine whether oral metronidazole, as part of preoperativ
e bowel preparation, prevents or decreases incidence of antibiotic-ass
ociated 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
. Ail patients underwent mechanical bowel preparation with polyethylen
e glycol-electrolyte lavage solution before administration of oral ant
ibiotics. Group 1 (n = 42) patients received three doses (1 g/dose) of
neomycin and erythromycin. Group 2 (n = 40) patients received three d
oses (1 g/dose) of neomycin and metronidazole. Both groups received on
e preoperative and three postoperative doses of intravenous cefotetan
(2 g/dose). Both groups had stool samples tested for C. difficile toxi
n in the preoperative and postoperative periods by enzyme-linked immun
oabsorbent assay or by tissue culture cytotoxicity. Patients with preo
perative stool studies positive for C. difficile were excluded from th
e study. RESULTS: Treatment groups were not different for age, gender,
or surgical procedure. Mean age +/- 1 standard deviation was 67.6 +/-
13.6 (range, 34-34) 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 stan
dard deviation was 9.76 +/- 4.9 (range, 4-28) days for Group 1 and 8.0
5 +/- 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 (neomy
cin and metronidazole) had positive stool studies for C. difficile. Re
lative risk of colonization with C. difficile in Group 1 was 4.76 time
s that in Group 2 (95 percent confidence interval, 0.581, 33). This di
fference was not statistically significant (P = 0.202). There were no
significant differences in C. difficile colonization rates with respec
t 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. diffici
le in this patient population undergoing colonic and rectal surgery.