• 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, and Sharon J Peacock.
• Medical Department, Sappasithiprasong Hospital, Ubon Ratchathani, Thailand.
• Antimicrob. Agents Chemother. 2005 Oct 1;49(10):4020-5.

AbstractMelioidosis (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.

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