Azithromycin, With or Without Loperamide, to Treat Travelers' Diarrhea
Information source: The University of Texas Health Science Center, Houston
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diarrhea
Intervention: Azithromycin 1000 mg or 500 mg (Drug); Loperamide 4 mg loading then 2 mg after each loose stool (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: The University of Texas Health Science Center, Houston Official(s) and/or principal investigator(s):
Charles D. Ericsson, MD, Principal Investigator, Affiliation: University of Texas Medical School at Houston
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.
Clinical Details
Official title: Loperamide Plus Azithromycin More Effectively Treats Travelers’ Diarrhea In Mexico Than Azithromycin Alone
Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Bio-equivalence Study
Primary outcome: Hours from beginning treatment to passage of last unformed stool
Secondary outcome: 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.
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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 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.
Locations and Contacts
University of Texas Enteric Disease Research Clinics, Guadalajara, Jalisco, Mexico
Additional Information
Related publications: Adachi JA, Ericsson CD, Jiang ZD, DuPont MW, Martinez-Sandoval F, Knirsch C, DuPont HL. Azithromycin found to be comparable to levofloxacin for the treatment of US travelers with acute diarrhea acquired in Mexico. Clin Infect Dis. 2003 Nov 1;37(9):1165-71. Epub 2003 Sep 30.
Starting date: June 2002
Ending date: August 2003
Last updated: August 1, 2006
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