Open, randomized therapeutic trial of six antimicrobial regimens in the treatment of human brucellosis. Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in the treatment of brucellosis in humans. Comparison of the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks versus streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis: a randomized clinical trial. Ofloxacin plus rifampicin versus doxycycline plus rifampicin in the treatment of brucellosis: a randomized clinical trial [ISRCTN11871179]. Comparison of three different combination therapies in the treatment of human brucellosis. Comparison of three different regimens in the treatment of acute brucellosis: a multicenter multinational study. Treatment of human brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin. A randomized, double-blind study. Comparison of doxycycline-streptomycin, doxycycline-rifampin, and ofloxacin-rifampin in the treatment of brucellosis: a randomized clinical trial. Ciprofloxacin and rifampicin versus doxycycline and rifampicin in the treatment of brucellosis.
This report describes the results of six antimicrobial regimens used for the treatment of brucellosis in an open, randomized study performed over two periods (1980-1983 and 1984-1987). In the first period, rifampicin and doxycycline were used for 4 weeks, trimethoprim-sulfamethoxazole for 6 months, and doxycycline for 6 weeks. During the second period, we used streptomycin for 2 or 3 weeks together with doxycycline for 6 weeks and rifampicin with doxycycline for 6 weeks. Comparison of the results showed the following: (1) no statistically significant findings were revealed when the different regimens were compared and (2) the regimens containing streptomycin yielded statistically more favorable results than those consisting of rifampicin and monotherapy when the patients treated with rifampicin were compared with those taking streptomycin and those receiving single-agent therapy. No significant differences were observed between monotherapeutic regimens and those including rifampicin. In the treatment of human brucellosis, antibiotic regimens containing an aminoglycoside are reportedly associated with fewer relapses.
                This prospective, randomized study employed doxycycline (100 mg administered orally twice daily for 45 days) in combination with either streptomycin (1 g administered intramuscularly daily for 14 days; the DS regimen) or gentamicin (5 mg/kg per day administered intramuscularly for 7 days; the DG regimen). Efficacy of treatment was determined by rates of failure or relapse with a follow-up period of 1 year.
                Ninety-seven patients with a mean age (+/- standard deviation [SD]) of 33.74+/-15.47 years and 94 patients with the a mean age (+/-SD) of 36.2+/-14.14 years were treated with regimens DG and DS, respectively (P = .277). The clinical manifestations in both groups of patients were similar with the exception of sweating, which was more common in the DG group (P = .04). Three (3.2%) of the patients in the DS group and 3 (3.1%) of patients in the DG group experienced relapse (difference, 0.1%; 95% confidence interval [CI], -4% to 5%; P = 1.0). Overall, 7 (7.4%) of the patients in the DS group and 5 (5.2%) of the patients in the DG group experienced failure of therapy or relapse (difference, 2.2%; 95% CI, -4.5% to 8.9%; P = .563). The actuarial probability for relapse at 12 months after completion of therapy was 4.3% in the DS group and 2.1% in the DG group (difference, 2.2%; 95% CI, -2.8% to 7.2%).
                The combination of oral doxycycline for 45 days plus intramuscular gentamicin for 7 days is equally as effective as traditional therapy using doxycycline for 45 days plus streptomycin for 14 days. To compare the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks with streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis.
                In each arm of the study, 82 patients older than 10 years randomly received 5 mg/kg gentamicin once daily for 5 days plus 100 mg of doxycycline twice daily for 8 weeks or 1 g of streptomycin intramuscularly for 2 weeks plus the same dose of doxycycline for 45 days. Therapeutic failure and relapse in these two treatment groups were compared. This study was registered in the Iranian Registry of Clinical Trials (www.irct.ir) with registration number ID: IRCT138708191441N1.
                The clinical manifestations in these two groups were similar. Therapeutic failure was seen in two (2.4%) patients in the gentamicin/doxycycline group and in four (4.9%) patients in the streptomycin/doxycycline group [relative risk (RR) = 0.5, 95% confidence interval (CI) 0.09-2.66, P = 0.68]. Relapse was seen in two (2.4%) cases in the gentamicin/doxycycline group and in five (6.1%) cases in the streptomycin/doxycycline group (RR = 0.4, 95% CI 0.08-2, P = 0.44). The efficacy with the gentamicin/doxycycline regimen was 95.12% and that with the streptomycin/doxycycline regimen was 89% (RR = 1.07, 95% CI 0.98-1.17, P = 0.25). Cox regression analyses showed no differences among the two treatment groups for patients who had relapse or therapeutic failure and those who had not regarding baseline covariates such as sex, duration of disease before diagnosis, positive blood culture and focal disease.
                The results show that the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks is not superior to that of streptomycin for 2 weeks plus doxycycline for 45 days. The combination therapies recommended by the World Health Organization for treatment of brucellosis are doxycycline plus rifampicin or doxycycline plus streptomycin. Although highly successful results have been obtained with these two regimens, relapse rates as high as 14.4%. The most effective and the least toxic chemotherapy for human brucellosis is still undetermined. The aim of the present study was to investigate the efficacy, adverse effects and cost of ofloxacin plus rifampicin therapy, and doxycycline plus rifampicin therapy and evaluate in the treatment of brucellosis.
                The open trial has been carried out prospectively by the two medical centers from December 1999 to December 2001 in Duzce region Turkey. The diagnosis was based on the presence of signs and symptoms compatible with brucellosis including a positive agglutination titre (>/=1/160) and/or a positive culture. Doxycycline and rifampicin group consisted of 14 patients who were given doxycycline 200 mg/day plus rifampicin 600 mg/day during 45 days and this group Ofloxacin plus rifampicin group was consisted of 15 patients who were given ofloxacin 400 mg/day plus rifampicin 600 mg/day during 30 days.
                Regarding clinical and/or demographic characteristics no significant difference was found between two groups of patients that underwent two different therapeutic regimens. At the end of the therapy, two relapses were seen in both groups (p = 0.695). Although duration of therapy was two weeks shorter in group treated with rifampicin plus ofloxacin, the cure rate was similar in both groups of examinees. Fever dropped more rapidly in the group that treated with rifampicin plus ofloxacin, 74 +/- 30 (ranges 48-216) vs. 106 +/- 26 (ranges 48-262) hours (p = 0.016).
                Ofloxacin plus rifampicin therapy has advantages of shorter treatment duration and provided shorter course of fever with treatment than in doxycycline plus rifampicin therapy. However, cost of ofloxacin plus rifampicin treatment is higher than doxycycline plus rifampicin treatment. Because of the similar effects, adverse effects and relapses rates between two regimens, we still advice doxycycline plus rifampicin for the treatment of brucellosis for countries, which have limited resources. The efficacy and tolerability of three different combination treatment regimens in human brucellosis were compared in 118 uncomplicated patients enrolled in a prospective study between May 1997 and December 2002. Brucellosis was diagnosed using standard clinical and microbiological findings. Patients with central nervous system involvement, spondylitis, endocarditis or children under 16 years of age were excluded from the study. Patients were randomly assigned to receive 400 mg of ofloxacin plus 600 mg of rifampicin (OR, n = 41), 200 mg of doxycycline plus 600 mg of rifampicin (DR, n = 45) or 1g intramuscularly streptomycin (administered for three weeks) plus 200 mg doxycycline (DS, n = 32) daily for 6 weeks. All patients were followed up at least 6 months after cessation of therapy. There was no statistical difference between the groups on relapse rates and clinical response to the treatment (P>0.05). Five patients in OR (12.8%), six patients in DR (14.3%) and three patients in DS groups (9.7%) suffered relapse. The side-effects were seen in eight (19.5%), 21 (46.7%) and eight (25.0%) patients of OR, DR and DS groups, respectively. The use of combination therapy of ofloxacin plus rifampicin for 6 weeks was found to be as effective as DR and DS. The side-effects of therapy in OR and DS groups was less severe than in the DR group. The present study was undertaken to evaluate efficacy, safety and patient acceptability of three antibiotic regimens for the treatment of acute brucellosis. Six different centres were involved: three in France, one in Greece and two in Spain. The regimens were: oral rifampicin 900 mg/day plus oral doxycycline 200 mg/day for 45 days (A), oral doxycycline 200 mg/day for 45 days plus im streptomycin 1 g/day for 21 days (regimen B) [corrected] and the WHO regimen (C) combining oral tetracycline 2 g/day for 21 days plus im streptomycin, 1 g/day, for 14 days. Regimens A and B were randomly allocated in all centres, while regimen C was allocated only in two centres. All patients were suffering from acute brucellosis clinically and biologically proven. 143 patients were allocated for treatment and analysed. Their mean age was 41 years (range 13-70), 49 were female and 94 male, and their mean weight was 64 kg (range 35-98). Among these patients, 14% had localized disease (nine orchitis, eight osteo-articular involvement and one pleural effusion), but there was no statistical difference between the three regimens in regard to this localized disease. Forty-five per cent of the patients had positive blood cultures. The cure rate with regimen A was 95%, 96% with regimen B and 59% with regimen C. Thus regimen A presented the same efficacy rate as regimen B, but regimen C cannot be regarded as the treatment of choice for acute brucellosis. To compare the effectiveness of doxycycline-rifampin (DR) combination therapy with that of the classic doxycycline-streptomycin (DS) combination in patients with brucellosis.
                A randomized, double-blind study, with a mean follow-up of 15.7 months.
                A 1000-bed teaching hospital in Barcelona, Spain.
                Ninety-five patients (68 men and 27 women; mean age, 39 years) diagnosed with brucellosis on the basis of both clinical and serologic findings; 81 of these patients had blood cultures positive for Brucella melitensis.
                Forty-four patients received doxycycline, 100 mg every 12 hours, and rifampin, 15 mg/kg body weight per day in a single morning dose, for 45 days; 51 patients received the same dose of doxycycline for 45 days plus streptomycin, 1 g/d for 15 days.
                Therapeutic failure and relapse during the follow-up period.
                The mean time to defervescence was 4.2 days for the DR group and 3.2 days for the DS group (P greater than 0.2). The actuarial probability of therapeutic failure or relapse at 12 months of follow-up (Kaplan-Meier) was 14.4% in the DR group and 5.9% in the DS group (difference, 8.5%; 95% Cl, -4.8% to 21.6%; P greater than 0.2). All three patients with spondylitis in the DR group failed therapy compared with one of four patients in the DS group. Excluding patients with spondylitis, the actuarial failure rate was 4.9% and 4.3% in the DR and DS groups, respectively, at 12 months of follow-up (difference, 0.6%; Cl, -8.1% to 9.4%; P greater than 0.2).
                Doxycycline-rifampin combination therapy for 45 days is as effective as the classic DS combination in most patients with brucellosis; however, DR therapy might be less effective in those patients with spondylitis. Traditional regimens for the treatment of brucellosis are associated with significant relapse rates. The aim of this study was to compare the efficacy of ofloxacin plus rifampin (OFX-RIF) versus doxycycline plus streptomycin (DOX-STR) and doxycycline plus rifampin (DOX-RIF) regimens in the treatment of brucellosis.
                Two hundred and nineteen patients with brucellosis were enrolled in a randomized clinical trial; 28 cases were withdrawn because they did not attend the follow-up. Out of 191 patients with brucellosis, 64 received OFX-RIF, 62 received DOX-RIF, and 65 patients received DOX-STR regimens. All patients were assessed during the period of therapy in the second, fourth, and sixth weeks by clinical course and were also followed up clinically and serologically for 6 months after the cessation of therapy.
                The highest clinical response (95.4%) was observed in the DOX-STR group (p=0.009). The results of multivariate analysis indicate that treatment with DOX-STR had the least therapeutic failures among the three groups (p=0.033). Adverse reactions were seen in 16.8% of patients, but there was no significant difference among the three groups (p=0.613). The lowest relapse rate (4.6%) was observed in the DOX-STR group (p=0.109).
                We conclude that the DOX-STR combination should remain the first-line regimen for the treatment of brucellosis in our region; we recommend DOX-RIF and OFX-RIF combinations as the second-line regimens.
                Copyright Â© 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. The present study was undertaken to evaluate the efficacy, safety, and patient tolerability of two antibiotic regimens for the treatment of brucellosis: rifampicin 600 mg/day and doxycycline 200 mg/day for 45 days (group 1), versus rifampicin 600 mg/day and ciprofloxacin 1 g/day for 30 days (group 2). Forty patients were diagnosed with brucellosis based on clinical and microbiological findings. The two groups were comparable regarding age and sex distribution. The average number of days without fever and symptoms was lower in group 2 patients than in group 1 patients (mean+/-SD: 3.85+/-1.98 for group 1 vs. 2.78+/-1.03 for group 2, P=0.044). During the 1-year follow-up period, three (15%) patients in group 2 and two (10%) patients in group 1 had clinical relapses; these rates were not significantly different. Ciprofloxacin and rifampicin treatment for brucellosis is as effective as the standard regimen of doxycycline and rifampicin and offers the advantage of a shorter duration of treatment.
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.