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.
To evaluate the effects of various antibiotic regimens, monotherapy or
in combination with other antibiotics, for treating human brucellosis.
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.
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
Data collection and analysis
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
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.
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.
Plain Language Summary
Brucellosis is a common infection caused by Brucella bacteria species
and can infect both people and animals. It is spread by eating infected
food products and through direct contact with infected animals. The
bacterial infection can affect different tissues and organs and is
treated using antibiotics. Current recommended treatment regimens
involve the use of two or more antibiotics in order to avoid relapses
occurring and to prevent prolonged use of these drugs, which may lead to
problems of drug resistance arising. Drug resistance is a particularly
important issue as most people infected with brucellosis live in low
socioeconomic areas of developing countries, where tuberculosis is also
an endemic health problem. Thus there are concerns over the potential
increase in resistance to tuberculosis drugs due to their prolonged use
in treating brucellosis.
This review evaluates different drug regimens for treatment of
brucellosis in terms of treatment failure and side effects: doxycycline
plus rifampicin, doxycycline plus streptomycin, quinolones plus
rifampicin or doxycycline plus gentamycin.
Based on currently available evidence, there is probably a lower
incidence of total drug treatment failure in people that take
doxycycline plus streptomycin instead of doxycycline plus rifampicin to
treat brucellosis. However, we are uncertain whether either one of these
two treatment regimens results in people having fewer adverse drug
There may not be any difference between the two drug regimens,
doxycycline plus rifampicin versus quinolones plus rifampicin, with
respect to total treatment failure. Notably, use of doxycycline plus
rifampicin instead of quinolones plus rifampicin may result in more
people suffering adverse drug reactions.
Giving doxycycline plus gentamycin to people with brucellosis may reduce
the incidence of total treatment failure compared to administration of
doxycycline plus streptomycin. However, comparing these two drug
regimens, there may not be any difference in the number of people that
have drug reactions.
Importantly studies included in this review were limited to adult
patients with brucellosis, and the findings of this review are not
applicable to children, pregnant women, and patients with complications
like spondylitis and neurobrucellosis. Some studies did not perform any
explicit assessment of minor adverse reactions, so the findings
regarding adverse drug reactions should be interpreted with caution.
Yousefi-Nooraie, R.; Mortaz-Hejri, S.; Mehrani, M.; Sadeghipour, P. Antibiotics for treating human brucellosis. Cochrane Database of Systematic Reviews (2012) (Issue 10) Art. No.: CD007179. [DOI: 10.1002/14651858.CD007179.pub2]
Antibiotics for treating human brucellosis