Azithromycin, With or Without Loperamide, to Treat Travelers' Diarrhea
关键词
抽象
描述
Background. The combination of loperamide and trimethoprim-sulfamethoxazole or a fluoroquinolone has proven to be more efficacious than the antimicrobial agent alone in the treatment of travelers' diarrhea. We set out to prove loperamide plus azithromycin was more efficacious that azithromycin alone.
Methods. During the summers of 2002-3, 176 US adults recently arrived in Guadalajara, Mexico were enrolled in a prospective, double-blinded, randomized trial of the treatment of acute diarrhea. Subjects received single doses (1000 mg or 500 mg) of azithromycin or a single 500 mg dose of azithromycin plus loperamide. Subjects gave a pre and post treatment stool sample for analysis and maintained daily diaries of symptoms and passage of stools.
Results. The MIC90 of azithromycin for all E. coli and Shigella was 0.03 and 4 µg/ml with eradication rates in day 5 stools of 88% and 100%, respectively. The duration of diarrhea was significantly (p=0.0002) shorter following treatment with azithromycin plus loperamide (11 h) than with either dose of azithromycin alone (34 h). In the first 24 h the average number of unformed stools passed was 3.4 (azithromycin-alone) and 1.2 (combination) for a significant (p<0.0001) difference of 2.2 unformed stools. This difference equated with 20% of azithromycin-treated subjects continuing to pass 6 or more unformed stools in the first 24 h post treatment compared with only 1.7% of combination-treated subjects.
Conclusions. For the treatment of travelers' diarrhea in an E. coli predominant region of the world a single 500 mg dose of azithromycin appeared as effective as a 1000 mg dose. Loperamide plus 500 mg azithromycin was safe and more effective than either dose of azithromycin. To realize the substantial clinical benefit that accrues to a subset of subjects, we feel loperamide should routinely be used in combination with an antimicrobial agent to treat travelers' diarrhea.
日期
| 最后验证: | 05/31/2015 |
| 首次提交: | 07/31/2006 |
| 提交的预估入学人数: | 07/31/2006 |
| 首次发布: | 08/02/2006 |
| 上次提交的更新: | 06/16/2015 |
| 最近更新发布: | 06/18/2015 |
| 实际学习开始日期: | 05/31/2002 |
| 预计主要完成日期: | 07/31/2003 |
| 预计完成日期: | 07/31/2003 |
状况或疾病
干预/治疗
Drug: Azithromycin 500 mg
Drug: Azithromycin 1000 mg plus Placebo
Drug: Azithromycin 500 mg plus Loperamide
Other: Placebo
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Active Comparator: Azithromycin 500 mg plus Placebo a single 500 mg dose of Azitrhomycin at the start of treatment; a single loading dose of placebo at the start of treatment and then a dose of placebo after each loose stool | |
| Active Comparator: Azithromycin 1000 mg plus Placebo a single 1000 mg dose of Azitrhomycin at the start of treatment; a single loading dose of placebo at the start of treatment and then a dose of placebo after each loose stool | Drug: Azithromycin 1000 mg plus Placebo A single 1000 mg dose at the start of treatment |
| Experimental: Azithromycin 500 mg plus Loperamide a single 500 mg dose of Azitrhomycin at the start of treatment; a single 4 mg loading dose of Loperamide at the start of treatment and then 2 mg Loperamide after each loose stool | Drug: Azithromycin 500 mg plus Loperamide A single 4 mg loading dose at the start of treatment and then 2 mg after each loose stool |
资格标准
| 有资格学习的年龄 | 18 Years 至 18 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - Eligible subjects included men or women, recently arrived in Mexico, at least 18 years of age, who developed acute diarrhea, which was defined as passage of 3 or more unformed stools in the preceding 24 hours accompanied by one or more signs or symptoms of enteric infection (e.g., nausea, vomiting, abdominal cramps, tenesmus, passage of grossly bloody stools or fecal urgency) with a duration of illness of less than or equal to 72 hours. Exclusion Criteria: - Exclusion criteria included pregnancy, breast feeding, an unstable medical condition, taking two or more doses of an antidiarrheal medication in the 24 hours before enrollment or any number of doses of symptomatic therapy within 2 hours of enrollment, or receiving an antimicrobial drug with expected activity against enteric bacterial pathogens within 7 days prior to enrollment. |
结果
主要结果指标
1. Hours from beginning treatment to passage of last unformed stool [subjects recorded the time and form of all stools passed during a 4 day observation period]
次要成果指标
1. Number of unformed stools passed per 24 hour period [24 hours after treatment]
2. Number of subjects with symptoms of enteric disease per 24 hour period [24 hours after treatment]
3. Number of treatment failures [72 hours after treatment]
4. Percent of subjects in whom enteropathogen isolated from an enrollment stool sample was eradicated from a day 5 stool [5 days after treatment]
5. Percent of subjects continuing to pass 3 or more (enrollment criteria) unformed stools in a 24 hour period [24 hours after treatment]
