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Open-label randomised trial of oral trimethoprim-sulfamethoxazole, doxycycline and chloramphenical compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis

Chaowagul, Wipada, Chierakul, Wirongrong, Simpson, Andrew J., Short, Jennifer M., Stepniewska, Kasia, Maharjan, Bina, Rajchanuvong, Adul, Busarawong, Duangkaew, Limmathurotsakul, Direk, Cheng, Allen C., Wuthiekanun, Vanaporn, Newton, Paul N., White, Nicholas J., Day, Nicholas P. J. and Peacock, Sharon J. (2005). Open-label randomised trial of oral trimethoprim-sulfamethoxazole, doxycycline and chloramphenical compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis. Antimicrobial Agents and Chemotherapy,49(10):4020-4025.

Document type: Journal Article
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Title Open-label randomised trial of oral trimethoprim-sulfamethoxazole, doxycycline and chloramphenical compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis
Author Chaowagul, Wipada
Chierakul, Wirongrong
Simpson, Andrew J.
Short, Jennifer M.
Stepniewska, Kasia
Maharjan, Bina
Rajchanuvong, Adul
Busarawong, Duangkaew
Limmathurotsakul, Direk
Cheng, Allen C.
Wuthiekanun, Vanaporn
Newton, Paul N.
White, Nicholas J.
Day, Nicholas P. J.
Peacock, Sharon J.
Journal Name Antimicrobial Agents and Chemotherapy
Publication Date 2005
Volume Number 49
Issue Number 10
ISSN 0066-4804   (check CDU catalogue open catalogue search in new window)
Start Page 4020
End Page 4025
Total Pages 6
Place of Publication Washington, United States
Publisher American Society for Microbiology
HERDC Category C1 - Journal Article (DEST)
Abstract 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.
DOI http://dx.doi.org/10.1128/AAC.49.10.4020-4025.2005   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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