Comparison between doxycycline-rifampin-amikacin and doxycycline-rifampin regimens in the treatment of brucellosis

Background: 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). Methods: 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 10mg/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. Results: Of the 228 patients enrolled, eight were withdrawn - four patients from the DR group and four from the ADR group.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). Conclusions: 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. © 2006 International Society for Infectious Diseases