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

doi:10.1136/bmj.39497.500903.25

BMJ, doi: 10.1136/bmj.39497.500903.25, (Published 5 March 2008)

Research

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

Keren Skalsky, student ¹, Dafna Yahav, resident ¹, Jihad Bishara, head of unit ²^,3, Silvio Pitlik, head of department ²^,3, Leonard Leibovici, head of department ¹^,3, Mical Paul, senior physician²^,3

¹ Internal Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva 49100, Israel, ² Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, ³ Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv 69978, Israel

Correspondence to: M Paul pil1pel{at}zahav.net.il

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

Design Systematic review and meta-analysis of randomised controlledtrials assessing different antibiotic regimens and durationsof 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 exclusioncriteria, data extraction, and assessment of methodologicalquality independently performed in duplicate. Primary outcomeswere relapse and overall failure resulting from primary failureor relapse. Relative risks with 95% confidence intervals werecalculated and pooled with a fixed effect model.

Results 30 trials and 77 treatment arms were included. Overallfailure was significantly higher with doxycycline-rifampicincompared to doxycycline-streptomycin, mainly due to a higherrate of relapse (relative risk 2.80, 95% confidence interval1.81 to 4.36; 13 trials, without heterogeneity). Results wereconsistent among patients with bacteraemia and complicated brucellosis.Doxycycline-streptomycin resulted in a significantly higherrate of failure than doxycycline-rifampicin-aminoglycoside (tripledrug regimen) (2.50, 1.26 to 5.00; two trials). Gentamicin wasnot inferior to streptomycin (1.45, 0.52 to 4.00 for failure;two trials). Quinolones combined with rifampicin were significantlyless effective than doxycycline combined with rifampicin orstreptomycin (1.83, 1.11 to 3.02, for failure; five trials).Monotherapy was associated with a higher risk of failure thancombined treatment when administered for a similar duration(2.56, 1.55 to 4.23; five trials). Treatment for six weeks ormore offered an advantage over shorter treatment durations.

Conclusions There are significant differences in effectivenessbetween currently recommended treatment regimens for brucellosis.The preferred treatment should be with dual or triple regimensincluding an aminoglycoside.

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