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Background: The optimal treatment regimen and duration of the therapy is still controversial in spinal brucellosis. The aim of this study is to compare the efficacy, adverse drug reactions, complications and cost of ciprofloxacin plus rifampicin versus doxycycline plus streptomycin in the treatment of spinal brucellosis., Methods: The patients diagnosed as spinal brucellosis between January 2002 to December 2004 were enrolled into the study. Patients were enrolled into the two antimicrobial therapy groups (doxycycline plus streptomycin vs. ciprofloxacin plus rifampicin) consecutively. For the cost analysis of the two regimens, only the cost of antibiotic therapy was analysed for each patient., Results: During the study period, 31 patients with spinal brucellosis were enrolled into the two antimicrobial therapy groups. Fifteen patients were included in doxycycline plus streptomycin group and 16 patients were included in ciprofloxacin plus rifampicin group. Forty-two levels of spinal column were involved in 31 patients. The most common affected site was lumbar spine (n = 32, 76%) and involvement level was not different in two groups. Despite the disadvantages (older age, more prevalent operation and abscess formation before the therapy) of the patients in the ciprofloxacin plus rifampicin group, the duration of the therapy (median 12 weeks in both groups) and clinical response were not different from the doxycycline plus streptomycin. The cost of ciprofloxacin plus rifampicin therapy was 1.2 fold higher than the cost of doxycycline plus streptomycin therapy., Conclusion: Classical regimen (doxycycline plus streptomycin), with the appropriate duration (at least 12 weeks), is still the first line antibiotics and alternative therapies should be considered when adverse drug reactions were observed.