In Turkey where diarrheagenic Escherichia coli are the major pathogens,4,5 the rate of protection against TD with rifaximin observed in this study (67%) was similar to that observed in a prior study by DuPont and colleagues6 among student

travelers to Mexico. The design of this study is unique from previous rifaximin prophylaxis trials because of the higher rifaximin daily dose (1,100 mg) administered. A safe and effective QD dosing regimen of rifaximin would be more convenient and potentially more cost effective versus a twice daily (BID) or three times daily (TID) dosing regimen. Although unclear, one wonders if a higher QD rifaximin dose of 1,100 mg might also have a residual protective impact seen with more frequent daily dosing regimen at lower rifaximin doses (eg, 200 mg BID or TID). Alternatively, QD scheduling at any dose may not be as effective as BID dosing given the possibility of a therapeutic trough with QD dosing, although in the DuPont and BAY 80-6946 molecular weight colleagues6 study, efficacy was observed with rifaximin 200 mg QD dosing. This study has important limitations including inadequate power due to lower than anticipated attack rate, limited microbiological outcomes, nonsequential treatment allocation, as well as issues of adherence ascertainment and to a lesser extent daily diary completion among enrollees. Despite these deficiencies, there was no discernable effect of the nonsequential treatment allocation on primary outcomes, although

such an effect cannot be ruled out. Furthermore, restricting

analysis to those for whom adequate signaling pathway adherence and outcome ascertainment could be assessed resulted in no appreciable change in the primary outcome with an estimated protective efficacy 71% (−34% to 94%; Fisher’s exact p = 0.14). Given the potential harms of long-term daily antibiotics in a population at risk for trauma-associated infections (including enteric trauma) and impact on individual and community microbiomes, it is uncertain that antimicrobial chemoprophylaxis would offer a practicable solution during most extended military deployments (which historically have averaged about 3–6 mo). However, Diflunisal there are a number of relevant settings including port visits, in special operations forces, or in the initial phase of deployment settings where risk of TD is highest and the consequences of heat injury are frequent, where chemoprophylaxis may offer an acceptable solution. Further studies to explore the efficacy and safety of TD chemoprophylaxis in these populations and settings are warranted. This study was supported by Salix Pharmaceuticals under a cooperative research and development agreement, and the Department of Defense Military Infectious Disease Research Program (Fort Detrick, MD, USA) under work unit no. 6000.RAD1.D.E0301. One or more authors of this article are military service members (or employees of the US Government). This work was prepared as part of official duties.