Effect of timing and duration of azithromycin therapy of leptospirosis in a hamster model

Objectives: Azithromycin is not associated with significant adverse effects or restricted usage in certain populations unlike standard antileptospirosis agents. In this study, the utility of short courses of azithromycin in treating or preventing leptospirosis was investigated in a lethal hamster model. Methods: All hamsters were infected intraperitoneally with 10⁵ leptospires. In experiment one, animals received 5 mg/kg of doxycycline or 10 mg/kg of azithromycin via intraperitoneal injection beginning on the second day after infection and continuing once daily for 1, 2, 3 or 5 days. In experiment two, animals received 1 or 2 day courses of azithromycin initiated 2 or 4 days following infection, or 4 days prior to infection. Results: All untreated control animals died between the sixth and ninth day following infection. In experiment one, survival rates in the doxycycline groups were 0, 50, 80 and 100% for those animals treated for 1, 2, 3 and 5 days, respectively. Except for the 1 day treatment group (which had an 80% survival), there was 100% survival in all azithromycin-treated groups. In experiment two, all animals treated after infection survived until study completion. No animals survived with 1 day of therapy started 4 days prior to infection while only 20% survived if they received 2 days. Conclusions: These results suggest short-course therapy with azithromycin, even started well after infection, is efficacious in preventing mortality from acute leptospirosis.