Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials.
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.
Skalsky
Keren
K
Internal Medicine E, Rabin Medical Center, Beilinson Hospital, Petah Tikva 49100, Israel.
Yahav
Dafna
D
Bishara
Jihad
J
Pitlik
Silvio
S
Leibovici
Leonard
L
Paul
Mical
M
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
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D015363:Quinolones; D013752:Tetracycline; D004318:Doxycycline; D012293:Rifampin; D013307:Streptomycin