Open-label randomized trial of oral trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol compared with trimethoprim-sulfamethoxazole and doxycycline for maintenance therapy of melioidosis.

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.

• Authors: Wipada Chaowagul, Wirongrong Chierakul, Andrew J Simpson, Jennifer M Short, Kasia Stepniewska, Bina Maharjan, Adul Rajchanuvong, Duangkaew Busarawong, Direk Limmathurotsakul, Allen C Cheng, Vanaporn Wuthiekanun, Paul N Newton, Nicholas J White, Nicholas P J Day, Sharon J Peacock
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 49 Issue 10 Pg. 4020-5 (Oct 2005) ISSN: 0066-4804 [Print] United States
• PMID: 16189075 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Anti-Infective Agents
• Chloramphenicol
• Trimethoprim, Sulfamethoxazole Drug Combination
• Doxycycline

Topics

• Adolescent
• Adult
• Aged
• Anti-Bacterial Agents (adverse effects, therapeutic use)
• Anti-Infective Agents (adverse effects, therapeutic use)
• Chloramphenicol (adverse effects, therapeutic use)
• Doxycycline (adverse effects, therapeutic use)
• Drug Therapy, Combination
• Drug Tolerance
• Female
• Humans
• Male
• Melioidosis (drug therapy, mortality)
• Middle Aged
• Recurrence
• Treatment Outcome
• Trimethoprim, Sulfamethoxazole Drug Combination (adverse effects, therapeutic use)