5%). The study synbiotic, AKSB, did not demonstrate a preventative effect against TD compared to placebo at the interim analysis (n = 174) and therefore study was halted. Although adherence to the study was less than expected, we also found no evidence that AKSB could reduce TD incidence in the 114 subjects who were fully protocol adherent. The study drug, AKSB, was found to be safe in all study participants including those older BYL719 than 60 years (n = 46). We also demonstrated good viability

of organisms within unused capsules indicating that the AKSB synbiotic was of high quality. Probiotic studies for the prevention of TD have indeed shown variable results. Briand and colleagues did not find a protective effect with the use of L acidophilus,[20] whereas other animal[21, 22] and human studies have shown a positive preventative effect of probiotics on TD.[11, 14] Similarly, in a recent meta-analysis, selleck compound only 50% of the randomized clinical trials reported efficacy in the prevention of TD. Efficacy was reported with S boulardii, and L rhamnosus GG.[11, 13-15] Compared to placebo, S boulardii[13] decreased the incidence of TD from 39% to 29%–34% but success depended directly on the rigorous use of the preparation and only

1016 of the 3000 (34%) participants completed the study. Despite the high incidence of TD in our study, only seven subjects demonstrated carriage of a pathogen post-travel. AKSB pill microbiologic assessment showed that the capsules still contained viable organisms although there was a decline in the total CFU of probiotic cAMP in approximately half of the pills returned. The medications were not required to be refrigerated but it is possible that travel to high temperature or humid climates may have affected the viability of the organisms. Limitations of this study include the lack of evidence of protocol adherence because the subjects were traveling and data were collected through self-reporting. Of those that reported compliance

only 58.2% were adherent to the protocol. There was no effective way to document reliability of the data entered into the daily diary. As less than half of the participants (43.8%) returned their pill bottles, post-travel pill count was not a reliable measure of compliance. Although there was a lack of protocol adherence, a trend toward benefit would have been expected toward reduction of TD incidence if the synbiotic had a beneficial effect. It is possible that the success of any TD prevention study will be fraught with such problems of compliance. Adherence to the study drugs (and real-life preventive medications) could potentially be increased with the use of individualized schedules, dosettes, and electronic-reminder devices including mobile smart phone-reminder utilization. These have been studied well in the HIV population for drug adherence.