title: Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis.
abstract: BACKGROUND
  Two antibiotic regimens are used commonly in Thailand for the initial treatment of severe melioidosis: ceftazidime in combination with trimethoprim-sulfamethoxazole (TMP-SMX) and ceftazidime monotherapy. It is not known whether TMP-SMX provides an additional benefit.
  
  
  METHODS
  Two prospective, randomized trials that compared these regimens for patients presenting with acute severe melioidosis were started independently at tertiary care hospitals in Ubon Ratchathani and Khon Kaen (in northeastern Thailand), and the results were analyzed together as a prospective, individual-patient data meta-analysis. The primary end point was in-hospital mortality rate.
  
  
  RESULTS
  The in-hospital mortality rate among all enrolled patients (n=449) was not significantly different between those randomized to ceftazidime alone (25.1%; 56 of 223 subjects) and those randomized to ceftazidime with TMP-SMX (26.6%; 60 of 226 subjects; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.7-1.7; stratified P=.73). Of the 241 patients with culture-confirmed melioidosis, 51 (21.2%) died. Of these 241 patients, 31 (12.9%) died > or =48 h after the time of study entry. Among patients with melioidosis, there was no difference in death rate between the 2 treatment groups for either all deaths (OR, 0.88; 95% CI, 0.48-1.6; stratified P=.70) or for deaths that occurred > or =48 h after hospital admission (OR, 0.88; 95% CI, 0.41-1.9; stratified P=.73). Conditional logistic regression analysis revealed that bacteremia, respiratory failure, and renal failure were independently associated with death and treatment failure. Drug regimens were not associated with death or treatment failure in this model.
  
  
  CONCLUSIONS
  We conclude that the addition of TMP-SMX to ceftazidime therapy during initial treatment of severe melioidosis does not reduce the acute mortality rate.
authors.affiliation: Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Wirongrong
authors.initials: W
authors.lastname: Chierakul
authors.forename: Siriluck
authors.initials: S
authors.lastname: Anunnatsiri
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Short
authors.forename: Bina
authors.initials: B
authors.lastname: Maharjan
authors.forename: Piroon
authors.initials: P
authors.lastname: Mootsikapun
authors.forename: Andrew J H
authors.initials: AJ
authors.lastname: Simpson
authors.forename: Direk
authors.initials: D
authors.lastname: Limmathurotsakul
authors.forename: Allen C
authors.initials: AC
authors.lastname: Cheng
authors.forename: Kasia
authors.initials: K
authors.lastname: Stepniewska
authors.forename: Paul N
authors.initials: PN
authors.lastname: Newton
authors.forename: Wipada
authors.initials: W
authors.lastname: Chaowagul
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Day
authors.forename: Ploenchan
authors.initials: P
authors.lastname: Chetchotisakd
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016957:Burkholderia pseudomallei / Q000187:drug effects; D002442:Ceftazidime / Q000009:adverse effects / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008554:Melioidosis / Q000188:drug therapy*; D008875:Middle Aged; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D002442:Ceftazidime