Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial.
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.


METHODS
Randomized, placebo-controlled, non-blinded trial.


METHODS
Six hundred-bed regional referral Veterans Affairs Medical Center.


METHODS
Thirty patients excreting C. difficile without diarrhea or abdominal symptoms.


METHODS
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.


METHODS
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 micrograms/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-positive at 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.
Johnson
S
S
Minneapolis Veterans Affairs Medical Center, Minnesota.
Homann
S R
SR
Bettin
K M
KM
Quick
J N
JN
Clabots
C R
CR
Peterson
L R
LR
Gerding
D N
DN
D000368:Aged; D015373:Bacterial Typing Techniques; D002353:Carrier State / Q000188:drug therapy*; D016360:Clostridioides difficile / Q000145:classification / Q000302:isolation & purification; D003015:Clostridium Infections / Q000188:drug therapy*; D003428:Cross Infection / Q000382:microbiology / Q000517:prevention & control; D004262:DNA Restriction Enzymes; D004761:Enterocolitis, Pseudomembranous / Q000517:prevention & control; D005243:Feces / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D000091402:Prohibitins; D014640:Vancomycin / Q000627:therapeutic use*
C000717331:PHB2 protein, human; D000091402:Prohibitins; D008795:Metronidazole; D014640:Vancomycin; D004262:DNA Restriction Enzymes