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Antimicrobial Agents and Chemotherapy, September 2007, p. 3259-3263, Vol. 51, No. 9
0066-4804/07/$08.00+0     doi:10.1128/AAC.00508-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Doxycycline versus Azithromycin for Treatment of Leptospirosis and Scrub Typhus

Udonthani Hospital, Udonthani Province, Thailand,¹ Chumphon Hospital, Chumphon Province, Thailand,² Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima Province, Thailand,³ Chaiyapoom Hospital, Chaiyapoom Province, Thailand,⁴ Banmai Chaiyapod Hospital, Bureerum Province, Thailand,⁵ Wellcome Trust-Mahidol University-Oxford University Tropical Medicine Research Programme, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand,⁶ Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand,⁷ National Research Institute of Animal Health, Ministry of Agriculture and Cooperative, Nondhaburi Province, Thailand,⁸ Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand,⁹ Ministry of Public Health, Thailand, Nondhaburi Province, Thailand,¹⁰

Received 14 April 2007/ Returned for modification 23 May 2007/ Accepted 6 July 2007

Leptospirosis and scrub typhus are important causes of acute fever in Southeast Asia. Options for empirical therapy include doxycycline and azithromycin, but it is unclear whether their efficacies are equivalent. We conducted a multicenter, open, randomized controlled trial with adult patients presenting with acute fever (<15 days), without an obvious focus of infection, at four hospitals in Thailand between July 2003 and January 2005. Patients were randomly allocated to receive either a 7-day course of doxycycline or a 3-day course of azithromycin. The cure rate, fever clearance time, and adverse drug events were compared between the two study groups. A total of 296 patients were enrolled in the study. The cause of acute fever was determined for 151 patients (51%): 69 patients (23.3%) had leptospirosis; 57 patients (19.3%) had scrub typhus; 14 patients (4.7%) had murine typhus; and 11 patients (3.7%) had evidence of both leptospirosis and a rickettsial infection. The efficacy of azithromycin was not inferior to that of doxycycline for the treatment of both leptospirosis and scrub typhus, with comparable fever clearance times in the two treatment arms. Adverse events occurred more frequently in the doxycycline group than in the azithromycin group (27.6% and 10.6%, respectively; P = 0.02). In conclusion, doxycycline is an affordable and effective choice for the treatment of both leptospirosis and scrub typhus. Azithromycin was better tolerated than doxycycline but is more expensive and less readily available.

Published ahead of print on 16 July 2007.

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