Azithromycin, With or Without Loperamide, to Treat Travelers' Diarrhea
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.
Drug: Azithromycin 1000 mg or 500 mg
Drug: Loperamide 4 mg loading then 2 mg after each loose stool
|Study Design:||Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||Loperamide Plus Azithromycin More Effectively Treats Travelers’ Diarrhea In Mexico Than Azithromycin Alone|
- Hours from beginning treatment to passage of last unformed stool
- Number of unformed stools passed per 24 h period.
- Number of subjects with no, mild, moderate or severe symptoms of enteric disease per 24 h period.
- Number of treatment failures.
- Number of subjects in whom an enteric bacterial pathogen isolated from an enrollment stool sample was eradicated from a day 5 stool.
- Percent of subjects continuing to pass 3 or more (enrollment criteria), or 6 or more (moderate to severe disease), unformed stools in a 24 h period.
|Study Start Date:||June 2002|
|Estimated Study Completion Date:||August 2003|
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.
|University of Texas Enteric Disease Research Clinics|
|Guadalajara, Jalisco, Mexico|
|Principal Investigator:||Charles D. Ericsson, MD||University of Texas Medical School at Houston|