Quinolones in treatment of human brucellosis: comparative trial of ofloxacin-rifampin versus doxycycline-rifampin. Ciprofloxacin and rifampicin versus doxycycline and rifampicin in the treatment of brucellosis. Comparison of three different regimens in the treatment of acute brucellosis: a multicenter multinational study. Comparison of the efficacy of two months of treatment with co-trimoxazole plus doxycycline vs. co-trimoxazole plus rifampin in brucellosis. Comparative trial of doxycycline plus streptomycin versus doxycycline plus rifampin for the therapy of human brucellosis. Efficacy of gentamicin plus doxycycline versus streptomycin plus doxycycline in the treatment of brucellosis in humans. Comparison between doxycycline-rifampin-amikacin and doxycycline-rifampin regimens in the treatment of brucellosis. Failure of prolonged treatment with ciprofloxacin in acute infections due to Brucella melitensis. Failure of ceftriaxone in the treatment of acute brucellosis. Treatment of human brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin. A randomized, double-blind study. Open, randomized therapeutic trial of six antimicrobial regimens in the treatment of human brucellosis. Ofloxacin plus rifampicin versus doxycycline plus rifampicin in the treatment of brucellosis: a randomized clinical trial [ISRCTN11871179]. 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. Comparison of three different combination therapies in the treatment of human brucellosis. Ampicillin in the treatment of brucellosis. A controlled therapeutic trial. Possible implications of doxycycline-rifampin interaction for treatment of brucellosis. Comparison of doxycycline-streptomycin, doxycycline-rifampin, and ofloxacin-rifampin in the treatment of brucellosis: a randomized clinical trial. Comparative study of two regimens in the treatment of brucellosis. A randomized, double-blind study to assess the optimal duration of doxycycline treatment for human brucellosis.
Quinolones have been reported to be active against Brucella species in vitro. In this prospective randomized study, the efficacy and safety of the combination of ofloxacin plus rifampin were compared with the efficacy and safety of doxycycline plus rifampin, both combinations administered for a 6-week period in treatment of brucellosis. Sixty-one patients were enrolled in the study, and 49 had blood or bone marrow cultures positive for Brucella melitensis. Thirty patients received 200 mg of doxycycline plus 600 mg of rifampin once daily, and 31 patients were treated with 400 mg of ofloxacin plus 600 mg of rifampin once daily for 6 weeks. Nine patients in each group had complications of the disease. There was one therapeutic failure in the ofloxacin-rifampin treatment group, and one patient from each group relapsed (3.3% of those in the doxycycline-rifampin treatment group versus 3.2% of those in the ofloxacin-rifampin treatment group). Gastric discomfort was the major side effect observed in 13 patients (43.3%) who received doxycycline plus rifampin, whereas only 2 patients (6.5%) treated with ofloxacin plus rifampin complained of gastric irritation. These results suggest that the combination of ofloxacin plus rifampin administered for 6 weeks is as effective as doxycycline plus rifampin given for the same period, regardless of the presence of complications of the disease. 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. 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 efficacy of two different regimens in treatment of brucellosis.
                This randomised clinical trial study was conducted on 280 patients with brucellosis in Babol, Iran, from April 1999 to January 2002. One of the following two regimens was randomly prescribed for two months: co-trimoxazole plus doxycycline (CD group) and co-trimoxazole plus rifampin (CR group).
                140 patients with the mean age of 35.56 (16.2) years, and 140 patients with the mean age of 31.39 (18) years, were treated with co-trimoxazole plus doxycycline and co-trimoxazole plus rifampin, respectively. Clinical manifestations and laboratory test results were similar in both groups (p >0.05), except in sex and clinical types (p <0.05). Failure of treatment was seen in 10 (7.1%) and 23 (16.4%) cases treated in the CD group and CR group, respectively (95% CI, 0.174 to 0.862; OR = 0.387; p = 0.020). Relapse was seen in 12 cases (8.6%) treated in the CD group and in 14 cases (10%) treated in the CR group (95% CI, 0.365 to 1.87; OR = 0.826; p = 0.646). Failure of treatment plus relapse was seen in 22 (15.7%) and 37 (26.4%) cases treated in the CD group and CR group, respectively (95%CI, 0.278 to 0.929, OR = 0.508; p = 0.028). Risk for developing of failure of treatment and relapse in patients treated with co-trimoxazole plus rifampin was 1.96 times higher than those treated with co-trimoxazole plus doxycycline. Among the relapsed patients, 18 (69.2%) cases occurred within 6 months after completion of therapy, and most of them in uncomplicated patients.
                Using two months of treatment, the efficacy of co-trimoxazole plus doxycycline is better than co-trimoxazole plus rifampin. Effectiveness and therapeutic value of the doxycycline plus streptomycin and doxycycline plus rifampin schedules of treatment of human brucellosis have been assessed by carrying out a prospective study on 111 patients randomly distributed into two groups. Patients in group A were treated with doxycycline plus streptomycin sulphate and those in group B with doxycycline plus rifampin. The temperature of all patients reverted to normal, and 54 patients from group A (91.6%) and 45 from group B (86.5%) achieved total recovery with a single therapeutic cycle. Two therapeutic failures and 3 relapses in group A (8.4%) and 7 relapses in group B (13.46%) were observed. The tolerance to both regimens was good. Although the combination doxycycline plus rifampin offers a more convenient oral administration, in the light of these results, until more extensive research is carried out, it should be considered as an alternative rather than a first choice in the treatment of human brucellosis. 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. Combination drug therapy of brucellosis leads to recovery of symptoms, shortening of symptomatic interval, and decrease in morbidity rate, but single drug therapy is associated with more relapse episodes and a higher rate of drug resistance. Different drug combinations have been evaluated in the treatment of brucellosis. Considering the failure of treatment and relatively high rate of relapse of the disease with the World Health Organization's (WHO) recommended therapeutic regimen, we evaluated a new regimen that we assumed would increase the success of treatment and decrease the rate of relapse. In this study we compare the standard regimen of the WHO, doxycycline-rifampin (DR), to triple therapy with doxycycline-rifampin-amikacin (ADR).
                Two hundred and twenty-eight consecutive patients with brucellosis, who attended Hamedan Sina Hospital between 1999 and 2001, whether seen as outpatients or as inpatients, were enrolled in the study. The participants were randomly allocated to the DR group (receiving doxycycline 100 mg twice a day and rifampin 10 mg/kg body weight/day every morning, both taken orally for eight weeks) or the ADR group (receiving doxycycline 100 mg twice a day and rifampin 10 mg/kg body weight/day every morning, both taken orally for eight weeks, plus 7.5 mg/kg amikacin intramuscularly twice a day for seven days). The patients were checked for the relief of symptoms, drug side-effects, and relapse of disease during the treatment and follow-up.
                Of the 228 patients enrolled, eight were withdrawn - four patients from the DR group and four from the ADR group. Of the remaining 220 participants (110 in the ADR group and 110 in the DR group), 107 were male (48.6%) and 113 were female (51.4%). Mean age was 35.7+/-17 years in the ADR group and 37+/-18.4 years in the DR group (p=0.5). In the DR group, 97 (88.2%) and in the ADR group, 106 (96.4%) of the patients had relief of symptoms (a significant difference by Chi-square test (p=0.04)). After completion of treatment, and at the sixth month follow-up, nine (9.3%) patients in the DR group and six (5.7%) in the ADR group experienced a relapse of the disease, with no significant difference (p=0.4). Mild side-effects were found in only 10 patients, and none required discontinuation of the therapeutic regimen. Of these patients, four were from DR group and six from ADR group; no significant difference was observed (p=0.7).
                Given the fact that the ADR regimen had a higher efficacy and more rapid action in terms of relief of symptoms compared to the DR regimen, and that no significant difference in drug side-effects and disease relapse existed in the patients of either group, adding amikacin to the DR standard treatment regimen seems beneficial. A randomized prospective, pilot study was performed to compare the efficacy of oral ciprofloxacin (750 mg or 1000 mg bd) with standard oral antimicrobial therapy (rifampicin plus doxycycline) in the treatment of acute infection with Brucella melitensis. All antimicrobial drugs were administered for 42 days. Although all patients responded rapidly, five of the six patients receiving ciprofloxacin relapsed following cessation of therapy. There were no relapses among the patients who received doxycycline/rifampicin. Despite its in-vitro activity against B. melitensis (MIC 0.5 mg/l), ciprofloxacin, administered twice daily, does not appear to constitute adequate therapy for acute brucellosis. In an open, multicenter study conducted in Israel in 1989, 18 patients with acute brucellosis were randomized to receive either less than or equal to 2 g of intramuscularly administered ceftriaxone daily for at least 2 weeks or doxycycline for 4 weeks plus streptomycin for 2 weeks. All 10 patients treated with the combination of doxycycline plus streptomycin responded promptly, and their infections did not relapse during 6 months of follow-up. Of eight patients treated with ceftriaxone, six did not respond initially; when ceftriaxone was replaced by the combination of doxycycline and streptomycin, patients responded immediately. No relapses of infection were observed in these patients during follow-up. One patient who received ceftriaxone responded and remained well at the end of 6 months of follow-up, and one patient who initially responded to therapy with this drug experienced relapse of infection within 3 weeks but recovered when the doxycycline/streptomycin regimen was initiated. We conclude that despite encouraging data from in vitro studies and promising clinical studies, 2 g of ceftriaxone administered im daily should not be considered appropriate therapy for 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. 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. 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. 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 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. nan We studied the possible interaction between rifampin and doxycycline in 20 patients with brucellosis treated randomly with either doxycycline and streptomycin or doxycycline and rifampin. The doxycycline levels in the plasma of patients in the group treated with rifampin were significantly lower than those in the plasma of patients treated with doxycycline and streptomycin. Furthermore, clearance in patients treated with rifampin was significantly higher than that in patients treated with doxycycline and streptomycin, and consequently, the elimination half-life and the area under the concentration-time curve were significantly lower. There was no therapeutic failure or relapse in the group treated with doxycycline and streptomycin, whereas 2 of 10 patients in the group treated with doxycycline and rifampin had a therapeutic failure or relapse. The plasma doxycycline levels had an inverse correlation with plasma rifampin levels. In the group treated with rifampin, those who were rapid acetylators had lower levels of doxycycline. In conclusion, combined treatment with rifampin reduces the levels of doxycycline in plasma. These data suggest that therapeutic failures or relapses may result from this interaction. 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. nan Human brucellosis is usually treated with a combination of tetracyclines and aminoglycosides. However, the optimal duration of therapy has not been clearly determined.
                We conducted a prospective, double-blind, randomized, multicenter study comparing treatment with doxycycline (100 mg po b.i.d.) for 30 days (30-day group) with the same dosage of doxycycline for 45 days (45-day group) in patients with brucellosis without endocarditis, spondylitis, or neurobrucellosis. All patients were treated with gentamicin (240 mg im once daily) for the first 7 days. Therapeutic outcome was evaluated by measuring relapse rates and drug safety.
                Seventy-three patients were included in each group. During the first 45 days after treatment, the percentage of patients with relapse was significantly higher in the 30-day group than in the 45-day group (12.3% vs. 1.37%; relative risk, 9.00; 95% confidence interval [CI], 1.17-69.2; P=.017). Between day 45 after treatment and 12 months after treatment, no further significant differences were found in relapse rates between groups (9.38% in the 30-day group vs. 11.11% in the 45-day group; relative risk, 0.84; 95% CI, 0.31-2.30; P=.78). Overall, relapses occurred in 15 (20.55%) of 73 patients in the 30-day group and in 9 (12.33%) of 73 patients in the 45-day group (relative risk, 1.67; 95% CI, 0.78-3.56; P=.264). Compliance and adverse effects were comparable in the 2 groups.
                Doxycycline treatment for 45 days significantly decreased early relapse rates among adults with brucellosis without increasing adverse effects.
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.