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Antimicrobial Agents and Chemotherapy, October 2005, p. 4020-4025, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4020-4025.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Open-Label Randomized Trial of Oral Trimethoprim-Sulfamethoxazole, Doxycycline, and Chloramphenicol Compared with Trimethoprim-Sulfamethoxazole and Doxycycline for Maintenance Therapy of Melioidosis

Wipada Chaowagul,1 Wirongrong Chierakul,2* Andrew J. Simpson,2,4 Jennifer M. Short,2,4 Kasia Stepniewska,2,4 Bina Maharjan,2 Adul Rajchanuvong,1 Duangkaew Busarawong,1 Direk Limmathurotsakul,2 Allen C. Cheng,2,3 Vanaporn Wuthiekanun,2 Paul N. Newton,2,4 Nicholas J. White,2,4 Nicholas P. J. Day,2,4 and Sharon J. Peacock2,4*

Medical Department, Sappasithiprasong Hospital, Ubon Ratchathani,1 Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand,2 Menzies School of Health Research, Charles Darwin University and Northern Territory Clinical School, Flinders University, Darwin, Australia,3 Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, Churchill Hospital, University of Oxford, Oxford OX3 7LJ, United Kingdom4

Received 10 March 2005/ Returned for modification 28 June 2005/ Accepted 24 July 2005

Melioidosis (infection caused by Burkholderia pseudomallei) requires a prolonged course of oral antibiotics following initial intravenous therapy to reduce the risk of relapse after cessation of treatment. The current recommendation is a four-drug regimen (trimethoprim [TMP], sulfamethoxazole [SMX], doxycycline, and chloramphenicol) and a total treatment time of 12 to 20 weeks. Drug side effects are common; the aim of this study was to compare the efficacy and tolerance of the four-drug regimen with a three-drug regimen (TMP-SMX and doxycycline). An open-label, randomized trial was conducted in northeast Thailand. A total of 180 adult Thai patients were enrolled, of which 91 were allocated to the four-drug regimen and 89 to the three-drug regimen. The trial was terminated early due to poor drug tolerance, particularly of the four-drug regimen. The culture-confirmed relapse rates at 1 year were 6.6% and 5.6% for the four- and three-drug regimens, respectively (P = 0.79). The three-drug regimen was better tolerated than the four-drug regimen; 36% of patients receiving four drugs and 19% of patients receiving three drugs required a switch in therapy due to side effects (P = 0.01). The duration of oral therapy was significantly associated with relapse; after adjustment for confounders, patients receiving less than 12 weeks of oral therapy had a 5.7-fold increase of relapse or death. A combination of TMP-SMX and doxycycline is as effective as and better tolerated than the conventional four-drug regimen for the oral treatment phase of melioidosis.

* Corresponding author. Mailing address: Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok 10400, Thailand. Phone: (66) 2-354-1395. Fax: (66) 2-354-9169. E-mail for Sharon J. Peacock: sharon{at}tropmedres.ac. E-mail for Wirongrong Chierakul: alwcr{at}diamond.mahidol.ac.th.

Antimicrobial Agents and Chemotherapy, October 2005, p. 4020-4025, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4020-4025.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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