Medicine E, Rabin Medical Center, Beilinson Hospital and Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Int J Antimicrob Agents. 2011 Jun;37(6):491-503. doi: 10.1016/j.ijantimicag.2010.11.029. Epub 2011 Feb 2.
β-Lactam-aminoglycoside combinations are commonly used despite lack of evidence of a clinical benefit. In this study, all randomised controlled trials (RCTs) assessing directly the clinical implications of synergism by comparing a β-lactam with the same β-lactam in combination with an aminoglycoside as empirical or definitive therapy for any type of infection and clinical scenario were compiled. A systematic search was undertaken to identify all trials regardless of language, date or publication status. The primary outcomes assessed were all-cause mortality and clinical failure regardless of antibiotic modifications. Risk of bias was evaluated and its effect was assessed through sensitivity analyses. Two reviewers applied inclusion criteria and extracted the data independently. A fixed-effect meta-analysis was performed. Fifty-two RCTs were identified assessing patients with febrile neutropenia, pneumonia, abdominal infections, bacteraemia, endocarditis or cystic fibrosis. Only five trials were double-blinded. All-cause mortality was similar with monotherapy versus combination therapy [risk ratio (RR)=0.96, 95% confidence interval (CI) 0.78-1.18, 28 trials, 3756 episodes]. Clinical failure regardless of antibiotic modifications was not significantly different (RR=0.88, 95% CI 0.74-1.05, 27 trials, 2500 episodes). Treatment failure including antibiotic addition/modification occurred more frequently with monotherapy (RR=1.20, 95% CI 1.12-1.28, 48 trials, 6643 episodes). There were no significant differences with regard to bacterial or fungal superinfections or development of antibiotic-resistant strains. Combination therapy resulted in a significantly higher incidence of adverse events, mainly nephrotoxicity. Overall, no clinical benefit was found for the use of a β-lactam with an aminoglycoside compared with a β-lactam alone. Treatment with β-lactams as monotherapy entailed more antibiotic regimen modifications in open trials.
β-内酰胺-氨基糖苷类联合用药尽管缺乏临床获益的证据，但仍被广泛应用。本研究汇集了所有直接评估协同作用对临床影响的随机对照试验（RCT），这些试验通过比较经验性或确定性治疗任何类型感染和临床情况时使用β-内酰胺类与相同β-内酰胺类联合氨基糖苷类的临床结局，来评估协同作用。进行了系统检索以确定所有试验，无论语言、日期或发表状态如何。主要结局评估为所有原因死亡率和临床失败，无论抗生素是否调整。评估了偏倚风险，并通过敏感性分析评估其影响。两名审查员应用纳入标准独立提取数据。进行固定效应荟萃分析。共确定了 52 项评估发热性中性粒细胞减少症、肺炎、腹部感染、菌血症、心内膜炎或囊性纤维化患者的 RCT。仅有 5 项试验为双盲。与单药治疗相比，联合治疗的全因死亡率相似[风险比（RR）=0.96，95%置信区间（CI）0.78-1.18，28 项试验，3756 例]。无论抗生素是否调整，临床失败率无显著差异（RR=0.88，95% CI 0.74-1.05，27 项试验，2500 例）。包括抗生素添加/调整在内的治疗失败在单药治疗中更常见（RR=1.20，95% CI 1.12-1.28，48 项试验，6643 例）。细菌或真菌感染或抗生素耐药株的发生率无显著差异。与单独使用β-内酰胺类相比，联合治疗导致不良事件发生率显著升高，主要为肾毒性。总体而言，与单独使用β-内酰胺类相比，β-内酰胺类与氨基糖苷类联合使用并未带来临床获益。开放性试验中单药使用β-内酰胺类需要更多抗生素方案调整。
