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JAC Advance Access originally published online on November 16, 2006
Journal of Antimicrobial Chemotherapy 2007 59(1):148-151; doi:10.1093/jac/dkl453
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

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

James E. Moon, Robert G. Rivard, Matthew E. Griffith, Roseanne A. Ressner, Suzanne McCall, Raven E. Reitstetter, Duane R. Hospenthal and Clinton K. Murray*

Departments of Medicine and Clinical Investigation, Brooke Army Medical Center Fort Sam Houston, TX, USA

Received 27 June 2006; returned 22 August 2006; revised 27 September 2006; accepted 13 October 2006

*Correspondence address. Infectious Disease (MCHE-MDI-7E), Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234, USA. Tel: +1-210-916-4355; Fax: +1-210-916-0388; E-mail: Clinton.Murray{at}amedd.army.mil

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.

Keywords: treatment , prophylaxis , animal model


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