Diarrhea
Conditions
Keywords
Diarrhea, Travel, Travelers' diarrhea, Azithromycin, Loperamide, Treatment, Antibiotic
Brief summary
In a previous study azithromycin proved as efficacious as levofloxacin in the treatment of travelers' diarrhea in Mexico. Because the addition of loperamide to some antibiotics (e.g., trimethoprim-sulfamethoxazole and ofloxacin) has proven more efficacious than antibiotic alone in the treatment of travelers' diarrhea, we decided to study the addition of loperamide to azithromycin. US adults with acute diarrhea in Guadalajara Mexico were randomized to receive azithromycin in two different doses or loperamide plus azithromycin. The duration of diarrhea was shorter (11 hours) in the combination-treated group compared to the antibiotic-treated groups (34 hours). The percentage of subjects continuing to pass 6 or more unformed stools in the first 24 hours was less (1.7%) in the combination-treated group than in the antibiotic-treated groups (20%). We feel loperamide should routinely be added to an antibiotic to optimize treatment of travelers' diarrhea.
Detailed description
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.
Interventions
A single 500 mg dose at the start of treatment
DRUGAzithromycin 1000 mg
A single 1000 mg dose at the start of treatment
DRUGLoperamide
A single 4 mg loading dose at the start of treatment and then 2 mg after each loose stool
OTHERPlacebo
A single loading dose at the start of treatment and then a dose after each loose stool
Sponsors
The University of Texas Health Science Center, Houston
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
*
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of unformed stools passed per 24 hour period | 24 hours after treatment | — |
| Number of subjects with symptoms of enteric disease per 24 hour period | 24 hours after treatment | Symptoms of enteric disease include nausea, vomiting, abdominal cramps, gas, urgency, and tenesmus. |
| Number of treatment failures | 72 hours after treatment | Treatment failure is defined as persisting ill after 72 hours |
| Percent of subjects in whom enteropathogen isolated from an enrollment stool sample was eradicated from a day 5 stool | 5 days after treatment | — |
| Percent of subjects continuing to pass 3 or more (enrollment criteria) unformed stools in a 24 hour period | 24 hours after treatment | — |
Countries
Mexico
Outcome results
None listed