title: Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials.
abstract: OBJECTIVE
  To determine and quantify differences in efficacy between treatment regimens for brucellosis.
  
  
  METHODS
  Systematic review and meta-analysis of randomised controlled trials assessing different antibiotic regimens and durations of treatment for human brucellosis.
  
  
  METHODS
  PubMed, CENTRAL, Lilacs, conference proceedings, and bibliographies with no restrictions on language, study year, or publication status. Review methods Search, application of inclusion and exclusion criteria, data extraction, and assessment of methodological quality independently performed in duplicate. Primary outcomes were relapse and overall failure resulting from primary failure or relapse. Relative risks with 95% confidence intervals were calculated and pooled with a fixed effect model.
  
  
  RESULTS
  30 trials and 77 treatment arms were included. Overall failure was significantly higher with doxycycline-rifampicin compared to doxycycline-streptomycin, mainly due to a higher rate of relapse (relative risk 2.80, 95% confidence interval 1.81 to 4.36; 13 trials, without heterogeneity). Results were consistent among patients with bacteraemia and complicated brucellosis. Doxycycline-streptomycin resulted in a significantly higher rate of failure than doxycycline-rifampicin-aminoglycoside (triple drug regimen) (2.50, 1.26 to 5.00; two trials). Gentamicin was not inferior to streptomycin (1.45, 0.52 to 4.00 for failure; two trials). Quinolones combined with rifampicin were significantly less effective than doxycycline combined with rifampicin or streptomycin (1.83, 1.11 to 3.02, for failure; five trials). Monotherapy was associated with a higher risk of failure than combined treatment when administered for a similar duration (2.56, 1.55 to 4.23; five trials). Treatment for six weeks or more offered an advantage over shorter treatment durations.
  
  
  CONCLUSIONS
  There are significant differences in effectiveness between currently recommended treatment regimens for brucellosis. The preferred treatment should be with dual or triple regimens including an aminoglycoside.
authors.affiliation: Internal Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva 49100, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Skalsky
authors.forename: Dafna
authors.initials: D
authors.lastname: Yahav
authors.forename: Jihad
authors.initials: J
authors.lastname: Bishara
authors.forename: Silvio
authors.initials: S
authors.lastname: Pitlik
authors.forename: Leonard
authors.initials: L
authors.lastname: Leibovici
authors.forename: Mical
authors.initials: M
authors.lastname: Paul
mesh_terms: D000617:Aminoglycosides / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002006:Brucellosis / Q000188:drug therapy*; D004318:Doxycycline / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006801:Humans; D015363:Quinolones / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012293:Rifampin / Q000627:therapeutic use; D013307:Streptomycin / Q000627:therapeutic use; D013752:Tetracycline / Q000627:therapeutic use
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D015363:Quinolones; D013752:Tetracycline; D004318:Doxycycline; D012293:Rifampin; D013307:Streptomycin