背景:在临床实践指南中,对于最初应向布鲁氏菌病患者提供的药物,尚无共识。为了提供翔实的证据,我们根据布鲁氏菌病药物的疗效和安全性进行了比较和排名.
方法:对于本系统综述和网络荟萃分析,我们搜索了4个英文数据库和3个中文数据库,从数据库开始到2023年12月13日。我们纳入了涉及儿童和青少年布鲁氏菌病的随机对照试验(RCTs),比较不同的抗生素方案。我们排除了明确针对脊柱炎布鲁氏菌病患者的研究,布鲁氏菌病心内膜炎,和神经布鲁氏菌病.主要结果是总体失败(疗效)和副作用(安全性)。次要结果是复发和治疗失败。首先检查了成对荟萃分析。数据采用随机效应网络荟萃分析,进行亚组和敏感性分析。网络荟萃分析(CINeMA)框架用于评估证据的确定性。该方案在PROSPERO(CRD42023491331)中预先注册。
结果:在通过数据库搜索确定的11,747条记录中,43项RCT纳入网络荟萃分析。与标准疗法(多西环素+利福平)相比,利福平+四环素(RR4.96;95%CI1.47~16.70;证据确定性极低),强力霉素+TMP/SMX(RR0.18;95%CI0.06~0.52;证据确定性低),强力霉素+喹诺酮类药物(RR0.27;95%CI0.11~0.71;证据确定性低),链霉素+四环素(RR0.04;95%CI0.01~0.16;证据确定性低),和单一(RR0.05;95%CI0.02~0.16;证据的中度确定性)效果较差。强力霉素+庆大霉素在疗效上排名最好(SUCRA值:0.94),第二个是三倍(SUCRA值:0.87),第三种是强力霉素+链霉素(SUCRA值:0.78)。
结论:布鲁氏菌病药物在疗效和安全性方面存在差异。强力霉素+庆大霉素,三倍,多西环素+链霉素具有优越的疗效和平安性。布鲁氏菌病的治疗应在疗效之间取得平衡,安全,和成本。
BACKGROUND: In clinical practice guidelines, there is no consensus about the medications that should be initially offered to patients with brucellosis. To provide informative evidence, we compared and ranked brucellosis medications based on their efficacy and safety.
METHODS: For this systematic review and network meta-analysis, we searched 4 English databases and 3 Chinese databases, from the date of database inception to December 13, 2023. We included randomized controlled trials (RCTs) involving children and adolescents with brucellosis, comparing different antibiotic regimens. We excluded studies explicitly targeting patients with spondylitis brucellosis, endocarditis brucellosis, and neuro-brucellosis. The primary outcomes were overall failure (efficacy) and side effects (safety). Secondary outcomes were relapse and therapeutic failure. Pairwise meta-analysis was first examined. Data were analyzed using random effects network meta-analysis, with subgroup and sensitivity analyses performed. The Confidence in Network Meta-Analysis (CINeMA) framework was used to assess the certainty of evidence. The protocol was preregistered in PROSPERO (CRD42023491331).
RESULTS: Of the 11,747 records identified through the database search, 43 RCTs were included in the network meta-analysis. Compared with standard therapy (Doxycycline + Rifampicin), Rifampicin + Tetracyclines (RR 4.96; 95% CI 1.47 to 16.70; very low certainty of evidence), Doxycycline + TMP/SMX (RR 0.18; 95% CI 0.06 to 0.52; low certainty of evidence), Doxycycline + Quinolones (RR 0.27; 95% CI 0.11 to 0.71; low certainty of evidence),
Streptomycin + Tetracyclines (RR 0.04; 95% CI 0.01 to 0.16; low certainty of evidence), and Single (RR 0.05; 95% CI 0.02 to 0.16; moderate certainty of evidence) were less efficacious. Doxycycline + Gentamicin ranked the best in efficacy (SUCRA values: 0.94), the second is Triple (SUCRA values: 0.87), and the third is Doxycycline +
Streptomycin (SUCRA values: 0.78).
CONCLUSIONS: Brucellosis medications differ in efficacy and safety. Doxycycline + Gentamicin, Triple, and Doxycycline +
Streptomycin have superior efficacy and safety. Treatment of brucellosis should strike a balance between efficacy, safety, and cost.