title: 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.affiliation: Medical Department, Sappasithiprasong Hospital, Ubon Ratchathani, Thailand.
authors.forename: Wipada
authors.initials: W
authors.lastname: Chaowagul
authors.forename: Wirongrong
authors.initials: W
authors.lastname: Chierakul
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Simpson
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Short
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Bina
authors.initials: B
authors.lastname: Maharjan
authors.forename: Adul
authors.initials: A
authors.lastname: Rajchanuvong
authors.forename: Duangkaew
authors.initials: D
authors.lastname: Busarawong
authors.forename: Direk
authors.initials: D
authors.lastname: Limmathurotsakul
authors.forename: Allen C
authors.initials: AC
authors.lastname: Cheng
authors.forename: Vanaporn
authors.initials: V
authors.lastname: Wuthiekanun
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002701:Chloramphenicol / Q000009:adverse effects / Q000627:therapeutic use*; D004318:Doxycycline / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008554:Melioidosis / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D002701:Chloramphenicol; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D004318:Doxycycline