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Treatment of Asymptomatic Clostridium difficile Carriers (Fecal Excretors) with Vancomycin or Metronidazole: A Randomized, Placebo-controlled Trial

Stuart Johnson, MD; Scott R. Homann, MD; Kristine M. Bettin, BS; Judith N. Quick, BA; Connie R. Clabots, MT; Lance R. Peterson, MD; and Dale N. Gerding, MD
[+] Article and Author Information

Grant Support: In part by the Department of Veterans Affairs and by the National Foundation for Infectious Diseases/Beecham Laboratories 1987 Postdoctoral Fellowship in Nosocomial Infection Research.

Requests for Reprints: Stuart Johnson, MD, Infectious Disease/111F, Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417.

Current Author Addresses: Drs. Johnson and Gerding and Ms. Bettin, Quick, and Clabots: Infectious Disease Section/111F, Department of Medicine, Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417.

Dr. Homann: Department of Biomedical Sciences, University of Illinois College of Medicine at Rockford, 1601 Parkview, Rockford, IL 61107.

Dr. Peterson: Department of Pathology, Wesley Pavilion, Room 564, Northwestern Memorial Hospital, 250 East Superior Street, Chicago, IL 60611.


Ann Intern Med. 1992;117(4):297-302. doi:10.7326/0003-4819-117-4-297
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Objective: To compare the efficacy of vancomycin and metronidazole for eradication of asymptomatic Clostridium difficile fecal excretion as a means of controlling nosocomial outbreaks of C. difficile diarrhea.

Design: Randomized, placebo-controlled, nonblinded trial.

Setting: Six hundred-bed regional referral Veterans Affairs Medical Center.

Patients: Thirty patients excreting C. difficilewithout diarrhea or abdominal symptoms.

Interventions: All patients were randomized to receive 10 days of oral vancomycin, 125 mg four times daily; metronidazole, 500 mg twice daily; or placebo, three times daily.

Measurements: Stool cultures were obtained during treatment and for 2 months after treatment. All C. difficile isolates were typed by restriction endonuclease analysis (REA).

Results: Clostridium difficile organisms were not detected during and immediately after treatment in 9 of 10 patients treated with vancomycin compared with 3 of 10 patients treated with metronidazole (P = 0.02) and 2 of 10 patients in the placebo group (P = 0.005). The fecal vancomycin concentration was 1406 ± 1164 µg/g feces, but metronidazole was not detectable in 9 of 10 patients. Eight of the nine evaluable patients who had negative stool cultures after treatment with vancomycin began to excrete C. difficile again 20 ± 8 days after completing treatment. Three of these patients received additional antibiotics before C. difficile excretion recurred, and five acquired new C. difficile REA strains. Four of six patients who received only vancomycin before C. difficile excretion recurred were culture-positiveat the end of the study compared with one of nine patients who received only placebo (P = 0.047).

Conclusions: Asymptomatic fecal excretion of C. difficile is transient in most patients, and treatment with metronidazole is not effective. Although treatment with vancomycin is temporarily effective, it is associated with a significantly higher rate of C. difficile carriage 2 months after treatment and is not recommended.

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