Rifaximin, a nonabsorbed oral antibiotic, prevents shigellosis after experimental challenge

Abstract

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.