Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis after experimental challenge.
BACKGROUND
This double-blind, placebo-controlled study was conducted to assess the efficacy of the nonabsorbed oral antibiotic rifaximin to prevent shigellosis in volunteers challenged with Shigella flexneri.


METHODS
Volunteers were randomized to receive either prophylactic rifaximin (200 mg 3 times daily for 3 days; n = 15) or placebo (n = 10) on days 0, 1, and 2. On day 1, volunteers were challenged with approximately 1500 colony-forming units of S. flexneri 2a strain 2457T given orally in sodium bicarbonate buffer.


RESULTS
The incidence of diarrhea was 0 with rifaximin, compared with 60% with placebo (P = .001). The median time to onset of diarrhea was 78.5 h with placebo (P < .001). The incidence of dysentery was 0 for rifaximin and 10% for placebo (P = .4). The incidence of colonization with Shigella was 0 with rifaximin, compared with 50% with placebo (P < .005). A significant serum or mucosal immune response after challenge by at least 1 indicator (immunoglobulin A titer, immunoglobulin G titer, and immunoglobulin A antibody-secreting cell count) was 0 with rifaximin and 80% with placebo (P < .001).


CONCLUSIONS
Rifaximin was effective and well tolerated, compared with placebo, in preventing shigellosis in this double-blind study of volunteers challenged with S. flexneri 2a.
Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. david.taylor@salix.com
David N
DN
Taylor
Robin
R
McKenzie
Anna
A
Durbin
Colleen
C
Carpenter
Christophe B
CB
Atzinger
Robert
R
Haake
A Louis
AL
Bourgeois
D000328:Adult; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000097:blood; D004311:Double-Blind Method; D004405:Dysentery, Bacillary / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D012294:Rifamycins / Q000378:metabolism / Q000627:therapeutic use*; D000078262:Rifaximin; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012294:Rifamycins; D000078262:Rifaximin