Systematic Review and Meta-Analysis of Randomized Clinical Trials in the Treatment of Human Brucellosis

Abstract

BackgroundBrucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance.Methods and FindingsA search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified.Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05–4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81–4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63–2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future.ConclusionsAlthough the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice.

Guidelines for the management of human brucellosis in the State of Paraná, Brazil

“…Thirteen studies comparing tetracycline associated with rifampin and tetracycline associated with gentamycin showed superiority of treatment with aminoglycosides (AII) 25 . These findings were confirmed by two more systematic reviews 26,27 . In the same year, a systematic review published by the Cochrane Group suggested the same treatment combination, however, with streptomycin as the aminoglycoside of choice 28 .…”

Outbreak of Human Brucellosis from Consumption of Raw Goats' Milk in Penang, Malaysia

“…8 Some patients were put on trimethoprim-sulfamethoxazole (160/800 mg BD) plus doxycycline. 7 Of the patients, 41% recovered fully, whereas 21% had a relapse that necessitated another course of oral treatment plus intramuscular streptomycin. Another one-third of the patients recovered but had sequelae, which included difficulty in walking and pain because of osteomyelitis or discitis from spinal infections.…”

“…7 If they had localized disease, they were prescribed the oral regimen as above plus intramuscular streptomycin (1 gm daily). 8 Some patients were put on trimethoprim-sulfamethoxazole (160/800 mg BD) plus doxycycline.…”

Renal Cyst Infection Caused byBrucella abortus

“…12 Although there are some cases seriesly reporting successful outcomes with quinolone including regimen, it is not supported by randomized clinical studies. 13,14 Even so, the long duration of unresponsiveness to doxycycline plus rifampicin pushed us also to add ciprofloxacin to the treatment according to the available antibiotic properties and reported case series. However, the success achieved with the applied therapy should be supported by randomized studies to recommend quinolones in the first-line therapy for cyst infections.…”