Single Dose Antibiotic Treatment of Acute Watery Diarrhea, Rifaximin Versus Azithromycin, With Loperamide Adjunct

Inclusion criteria

• Active duty military, 18-60 years old
• Presence of acute watery diarrhea (3 or more loose/liquid stools in 24 hours or 2 loose/liquid stools in 24 hours and associated symptoms such as nausea, vomiting, abdominal cramps or tenesmus) lasting <96 hours in duration that impacts function in activities and/or performance of primary duties. Refer to recruitment decision tree below.
• Eligible for ambulatory management. (Note: Ambulatory management in this study means that the patient can be treated on an outpatient basis to include up to 23 hours of medical observation and IV therapies.)
• Able to comply with follow-up procedures.
• Will remain in country for at least 7 days or an assurance that follow-up can be arranged elsewhere.

Exclusion criteria

• Allergy to rifamycins, macrolides, or loperamide (not including mild gastrointestinal upset).
• Antibiotic therapy in the 72 hours prior to presentation (excluding malaria prophylaxis with mefloquine, malarone, chloroquine/proguanil, tafenoquine, or doxycycline).
• Concomitant medications with known drug-drug interactions with any of the study drugs (includes theophylline, digoxin, warfarin, chloroquine and hydroxychloroquine).
• Current or history of liver disease or other serious health conditions based on review by study physician.
• Acute dysentery and/or febrile illness (temperature > 100.4°F [38.1°C]).
• Presence of symptoms >96 hours prior to initiating treatment.
• Use of >4 mg loperamide or use of any amount of loperamide for greater than 24 hours prior to enrollment. Prior use of bismuth subsalicylate or other anti-diarrheal, non-antibiotic therapy in the 48 hours prior to enrollment.
• Positive pregnancy test at presentation (unknown effects with rifaximin). All female participants will be administered a urine pregnancy test prior to enrollment.
• Previously screened or randomized in this study.