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Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials

BMJ 2008; 336 doi: (Published 27 March 2008) Cite this as: BMJ 2008;336:701
  1. Keren Skalsky, student 1,
  2. Dafna Yahav, resident 1,
  3. Jihad Bishara, head of unit 23,
  4. Silvio Pitlik, head of department 23,
  5. Leonard Leibovici, head of department 13,
  6. Mical Paul, senior physician23
  1. 1Internal Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva 49100, Israel
  2. 2Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital
  3. 3Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel
  1. Correspondence to: M Paul pil1pel{at}
  • Accepted 4 February 2008


Objectives To determine and quantify differences in efficacy between treatment regimens for brucellosis.

Design Systematic review and meta-analysis of randomised controlled trials assessing different antibiotic regimens and durations of treatment for human brucellosis.

Data sources 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.


  • We thank M Akova, Y Bayindir, and O Karabay for supplying additional data on their trials. Data for Dorado Pombo et alw78 were obtained from a previously published meta-analysis by Solera et al.10

  • Contributors: DY, MP, and LL were responsible for conception and design. KS, DY, and MP searched for and retrieved articles and extracted and analysed data. KS, DY, LL, and MP were responsible for interpretation and writing. JB and SP critically revised the manuscript, which was approved by all authors. MP is guarantor.

  • Funding: None.

  • Competing interests: None declared.

  • Ethics approval: Not required.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Accepted 4 February 2008
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