Trial Evaluating Ambulatory Therapy of Travelers' Diarrhea (TrEAT TD) Study: A Randomized Controlled Trial Comparing 3 Single-Dose Antibiotic Regimens With Loperamide
Mark S Riddle, Patrick Connor, Jamie Fraser, Chad K Porter, Brett Swierczewski, Emma J Hutley, Brook Danboise, Mark P Simons, Christine Hulseberg, Tahaniyat Lalani, Ramiro L Gutierrez, David R Tribble, TrEAT TD Study Team, Matthew Adam, Ernest Akorli, Rachael Armstrong, Lucy Ashford-Brown, Jaime Alvarado, Ricardo Aviles, Charlotte Ayres, Timothy Ballard, Liam Barry, Mary Bavaro, Catherine Berjohn, Robert Bjoraker, Peter Blenkinsop, Jason Blitz, Jeromy Boucher, Timothy Burgess, Daniel Burns, Jenna Burns, Shauna Butler, Anthony Cancio, Anthony Cardile, Tarah Carnes, Fongkuei Cheng, Katherine Clay, David Cook, Robert Deiss, Charles Duffield, Christopher Duplessis, Rhonda Dyer, Aaron Farmer, Robert Gormley, Antonia Hazlerigg, Jewell Hemmings, Neil Hill, Emily Hollis, Jack Hutter, Alshia Johnson, Paul Kartchner, Fred Kency Jr, Kelly Latimer, Julian Lentaigne, Andrew Letizia, Jason Maguire, Jennifer Masel, Ryan Maves, Aline Miura, Lynette Moore, Olamide Oladipo, Shane Patterson, Mark Pence, Adrian Proffitt, Joanna Rimmer, Benjamin Rodriguez, Carlo Rossi, Claire Royston, Melanie Sanders, Karen Santiago, Thomas Scorer, Amanda Self, Akira Shishido, Mildred Sitonik, Daniel Snyder, Garrick Stride, Hamilton Tilley, Matthew Timlin, Melanie Trado, Detonya Tulsie, Lavanya Viswanathan, Tyler Warkentien, J T A Wedgwood, Samuel White, Mark S Riddle, Patrick Connor, Jamie Fraser, Chad K Porter, Brett Swierczewski, Emma J Hutley, Brook Danboise, Mark P Simons, Christine Hulseberg, Tahaniyat Lalani, Ramiro L Gutierrez, David R Tribble, TrEAT TD Study Team, Matthew Adam, Ernest Akorli, Rachael Armstrong, Lucy Ashford-Brown, Jaime Alvarado, Ricardo Aviles, Charlotte Ayres, Timothy Ballard, Liam Barry, Mary Bavaro, Catherine Berjohn, Robert Bjoraker, Peter Blenkinsop, Jason Blitz, Jeromy Boucher, Timothy Burgess, Daniel Burns, Jenna Burns, Shauna Butler, Anthony Cancio, Anthony Cardile, Tarah Carnes, Fongkuei Cheng, Katherine Clay, David Cook, Robert Deiss, Charles Duffield, Christopher Duplessis, Rhonda Dyer, Aaron Farmer, Robert Gormley, Antonia Hazlerigg, Jewell Hemmings, Neil Hill, Emily Hollis, Jack Hutter, Alshia Johnson, Paul Kartchner, Fred Kency Jr, Kelly Latimer, Julian Lentaigne, Andrew Letizia, Jason Maguire, Jennifer Masel, Ryan Maves, Aline Miura, Lynette Moore, Olamide Oladipo, Shane Patterson, Mark Pence, Adrian Proffitt, Joanna Rimmer, Benjamin Rodriguez, Carlo Rossi, Claire Royston, Melanie Sanders, Karen Santiago, Thomas Scorer, Amanda Self, Akira Shishido, Mildred Sitonik, Daniel Snyder, Garrick Stride, Hamilton Tilley, Matthew Timlin, Melanie Trado, Detonya Tulsie, Lavanya Viswanathan, Tyler Warkentien, J T A Wedgwood, Samuel White
Abstract
Background: Recommended treatment for travelers' diarrhea includes the combination of an antibiotic, usually a fluoroquinolone or azithromycin, and loperamide for rapid resolution of symptoms. However, adverse events, postdose nausea with high-dose azithromycin, effectiveness of single-dose rifaximin, and emerging resistance to front-line agents are evidence gaps underlying current recommendations.
Methods: A randomized, double-blind trial was conducted in 4 countries (Afghanistan, Djibouti, Kenya, and Honduras) between September 2012 and July 2015. US and UK service members with acute watery diarrhea were randomized and received single-dose azithromycin (500 mg; 106 persons), levofloxacin (500 mg; 111 persons), or rifaximin (1650 mg; 107 persons), in combination with loperamide (labeled dosing). The efficacy outcomes included clinical cure at 24 hours and time to last unformed stool.
Results: Clinical cure at 24 hours occurred in 81.4%, 78.3%, and 74.8% of the levofloxacin, azithromycin, and rifaximin arms, respectively. Compared with levofloxacin, azithromycin was not inferior (P = .01). Noninferiority could not be shown with rifaximin (P = .07). At 48 and 72 hours, efficacy among regimens was equivalent (approximately 91% at 48 and 96% at 72 hours). The median time to last unformed stool did not differ between treatment arms (azithromycin, 3.8 hours; levofloxacin, 6.4 hours; rifaximin, 5.6 hours). Treatment failures were uncommon (3.8%, 4.4%, and 1.9% in azithromycin, levofloxacin, and rifaximin arms, respectively) (P = .55). There were no differences between treatment arms with postdose nausea, vomiting, or other adverse events.
Conclusions: Single-dose azithromycin, levofloxacin, and rifaximin with loperamide were comparable for treatment of acute watery diarrhea.
Clinical trial registration: NCT01618591.
Keywords: azithromycin; levofloxacin; randomized control trial; rifaximin; travelers’ diarrhea.
Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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Source: PubMed