Better efficacy of triple antibiotics therapy for human brucellosis: A systematic review and meta-analysis

Background: The treatment of brucellosis suffers from a high recurrence rate and drug resistance. Our study researched the differences in efficacy and side effects between triple antibiotics therapy and dual antibiotics therapy in the treatment of brucellosis through a systematic review and meta-analysis. Methods: We searched 4 English electronic databases and 2 Chinese electronic databases for randomized controlled trials and cohort studies published through September 2022 on the use of triple antibiotics versus dual antibiotics in the treatment of brucellosis. Overall outcome indicators were therapeutic failure rate, relapse rate, overall therapeutic failure rate, and side effect rate. Relative risk (RR) and 95% confidence intervals (95% CIs) were used as summary statistics. A fixed-effects model was used to combine the overall effect sizes. Results: The meta-analysis included 15 studies consisting of 11 randomized controlled trials and 4 cohort studies. Triple antibiotics showed better efficacy than dual antibiotics in a comparison of 3 overall outcome indicators (therapeutic failure rate (RR 0.42; 95% CI 0.30 to 0.59 heterogeneity P = 0.29, I2 = 15%), relapse rate (RR 0.29; 95% CI 0.18 to 0.45 heterogeneity P = 0.88, I2 = 0%), and overall therapeutic failure rate (RR 0.37; 95% CI 0.28 to 0.48 heterogeneity P = 0.35, I2 = 9%)). The incidence of side effects in patients with brucellosis treated with triple antibiotics was not significantly different from that in brucellosis patients treated with dual antibiotics (RR 0.85; 95% CI 0.67 to 1.06 heterogeneity P = 0.1, I2 = 35%). Sensitivity analyses showed robust results and Peter’s test showed no publication bias. The results of subgroup analyses for the research type, drugs, and type of brucellosis were largely consistent with the overall outcome indicators, indicating the reliability and robustness of the overall results. Conclusions: In the treatment of brucellosis, triple antibiotics have better efficacy than dual antibiotics and do not increase the incidence of side effects. Author summary: Brucellosis is a major public health problem in the world. Although rarely fatal, the disease has a tendency to be chronic and persistent, becoming a granulomatous disease capable of affecting any organ system. Therefore, in addition to other control interventions, it is particularly important to provide timely and effective treatment after its occurrence. The current treatment for brucellosis is the dual antibiotics regime recommended by the WHO in 1986 (doxycycline combined with streptomycin or rifampicin). However, classical therapy has a high recurrence rate and increasing rates of drug resistance. In recent years, studies combined classical therapy with another aminoglycoside or quinolone that is triple antibiotic therapy to treat brucellosis, which achieved significant efficacy and no remarkable difference in the incidence of side effects compared to dual antibiotic therapy. Conversely, studies have also found that triple therapy has the same efficacy as dual therapy. In the above context, our study compared the efficacy and safety between the 2 therapies in the treatment of brucellosis, founding that triple antibiotics had better efficacy compared to dual antibiotics and there was no increase in the rate of side effects; both subgroup and sensitive analyses showed that the results were reliable and robust; Peter’s test showed no publication bias in studies. Finally, our study aims to provide an evidence-based basis for treatment options for brucellosis.