Antibiotics for treating human brucellosis.
BACKGROUND
Brucellosis is the most common zoonotic infection in the world. Several antibiotics, separately or in combination, have been tried for treatment of human brucellosis. The inconsistencies between different treatment regimens warrants the need for a systematic review to inform clinical practice and future research.


OBJECTIVE
To evaluate the effects of various antibiotic regimens, monotherapy or in combination with other antibiotics, for treating human brucellosis.


METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and LILACS until May 2012. We browsed the abstract books of several international infectious diseases conferences. We also checked the reference lists of all studies identified


METHODS
We included the randomized controlled trials on the pharmaceutical interventions in treatment of acute, chronic, non-complicated, and complicated human brucellosis. The outcomes of interest were relapse, persistence of symptoms at the end of treatment, and adverse drug effects.


METHODS
Two authors independently assessed the studies for inclusion, risk of bias, and extracted relevant data using pre-designed extraction forms. The findings of homogenous studies were pooled using fixed-effect meta-analysis.


RESULTS
In total we included 25 studies comparing various antibiotic regimens. Methods of allocation and concealment were inadequately described in half the studies, and only three were blinded. In comparisons of doxycycline plus rifampicin versus doxycycline plus streptomycin we found eight studies with 694 participants. For treatment failure, the doxycycline plus rifampicin regimen was less effective (risk ratio (RR) 1.91, 95% confidence interval (CI) 1.07 to 3.42, seven studies, 567 participants), relapse (RR 2.39, 95% CI 1.17 to 4.86), and minor adverse drug reactions (RR 1.38, 95% CI 0.99 to 1.92). In comparisons of doxycycline plus rifampicin against quinolone (ciprofloxacin or ofloxacin) plus rifampicin we found five studies of 336 participants. The pooled analysis did not demonstrate any significant difference between two regimens in terms of relapse and symptom persistence, but showed a non-significant higher risk of minor adverse reactions in doxycycline plus rifampicin (RR 1.80, 95% CI 0.78 to 4.18). Other comparisons were reported in a few heterogenous studies, and the pooled analyses, where applied, did not show any significant difference.


CONCLUSIONS
Doxycycline (six weeks) plus streptomycin (two or three weeks) regimen is more effective regimen than doxycycline plus rifampicin (six weeks) regimen. Since it needs daily intramuscular (IM) injection, access to care and cost are important factors in deciding between two choices. Quinolone plus rifampicin (six weeks) regimen is slightly better tolerated than doxycycline plus rifampicin, and low quality evidence did not show any difference in overall effectiveness.
Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada. yousefr@mcmaster.ca.
Reza
R
Yousefi-Nooraie
Sameh
S
Mortaz-Hejri
Mehdi
M
Mehrani
Parham
P
Sadeghipour
D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002006:Brucellosis / Q000188:drug therapy*; D002939:Ciprofloxacin / Q000627:therapeutic use; D004318:Doxycycline / Q000627:therapeutic use; D006801:Humans; D015242:Ofloxacin / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012293:Rifampin / Q000627:therapeutic use; D013307:Streptomycin / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D015242:Ofloxacin; D004318:Doxycycline; D012293:Rifampin; D013307:Streptomycin