By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.

Source: Tribble DR, et al. Traveler's diarrhea in Thailand: randomized, double-blind trial comparing single-dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen. Clin Infect Dis. 2007; 44:338-346.

Synopsis: A randomized trial found that the optimal therapy for empiric treatment of diarrhea acquired by travelers in Thailand was a single 1 gram dose of azithromycin.

U.S. military personnel in Thailand presenting with the acute onset of diarrhea were randomized to treatment with one of 3 regimens: a single 1 g dose of azithromycin, 500 mg of azithromycin daily for 3 days, or 500 mg levofloxacin daily for 3 days. One or more enteric pathogen was identified in 81% of patients of the 156 patients, with Campylobacter accounting for 64% of this group. All the Campylobacter isolates were susceptible to azithromycin (MIC90, 0.094 mcg/ml), while 50% were resistant to levofloxacin. Of the 28 Salmonella isolates, 14% were resistant to azithromycin while none were resistant to azithromycin. There were 18 enteropathogenic Escherichia coli isolates; 3.8% and 5.6% were resistant to levofloxacin and azithromycin, respectively. All 11 Plesiomonas isolates were susceptible to both antibiotics.

The cure rate at 72 hours among azithromycin recipients in an intent-to-treat analysis was 94% in the single dose group and 80% in the 3 day treatment group, but only 70% in those given levofloxacin for 3 days (P = 0.001). The one day azithromycin treatment was significantly superior to the 3 day regimen (P = 0.04). The mean duration of diarrhea after the first dose of antibiotic was 39 hours and 43 hours in the single and multiple dose azithromycin groups and 43 hours in those treated with the fluoroquinolone.

Microbiological eradication was achieved in 96% -100% of azithromycin recipients and only 38% of those given levofloxacin (P = 0.001), but there was only a weak correlation between pathogen eradication and clinical response. Although many subjects were receiving doxycycline as malaria prophylaxis, analysis determined that this did not appear to affect the results. Treatment was well tolerated, although nausea after the first treatment dose occurred significantly more frequently in individuals who received a single 1-g dose of azithromycin.

Commentary

The recently published recommendations of the Infectious Disease Society for the management of traveler's diarrhea1 can be summarized as follows:

*Pre-travel management includes education and advice about prevention, food and liquid hygiene, and provision of self-treatment if diarrhea occurs.

*Self-treatment is multi-component and includes hydration, the use of loperamide for symptom control when necessary (but in the absence of temperature > 38.5° C, and a short course of antibiotics.

*Therapy with a single dose or up to 3 days of therapy with a fluoroquinolone is generally recommended, but in travelers to destinations (Southeast and South Asia) with a high prevalence of fluoroquinolone-resistant Campylobacter infections, "azithromycin may be indicated."

This study confirms the efficacy of azithromycin in the treatment of traveler's diarrhea as well as its superiority to levofloxacin in a location with significant fluoroquinolone resistance among ampylobacter isolates. Unfortunately, such resistance is not confined to Thailand, having been recognized in other parts of Asia and, more recently, in South America and Africa. Azithromycin has also been demonstrated to be effective in the treatment of typhoid fever, including cases caused by multidrug resistant isolates.2