Antibiotics for treating human brucellosis

Abstract

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. Objectives To evaluate the effects of various antibiotic regimens, monotherapy or in combination with other antibiotics, for treating human brucellosis. Search 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. Selection criteria 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. 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 meta-analysis. Main 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. Authors' 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. 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 reactions. 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