Azithromycin, With or Without Loperamide, to Treat Travelers' Diarrhea
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.
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.
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.