Department of Molecular Biology & Microbiology, Tufts University School of Medicine, United States; Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, United States.
Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, United States; Graduate School of Biomedical Sciences, Tufts University School of Medicine, United States.
Curr Opin Microbiol. 2021 Dec;64:68-75. doi: 10.1016/j.mib.2021.09.006. Epub 2021 Oct 8.
Interest in antibiotic combination therapy is increasing due to antimicrobial resistance and a slowing antibiotic pipeline. However, aside from specific indications, combination therapy in the clinic is often not administered systematically; instead, it is used at the physician's discretion as a bet-hedging mechanism to increase the chances of appropriately targeting a pathogen(s) with an unknown antibiotic resistance profile. Some recent clinical trials have been unable to demonstrate superior efficacy of combination therapy over monotherapy. Other trials have shown a benefit of combination therapy in defined circumstances consistent with recent studies indicating that factors including species, strain, resistance profile, and microenvironment affect drug combination efficacy and drug interactions. In this review, we discuss how a careful study design that takes these factors into account, along with the different drug interaction and potency metrics for assessing combination performance, may provide the necessary insight to understand the best clinical use-cases for combination therapy.
由于抗菌药物耐药性的出现和抗生素研发管线的放缓，人们对抗生素联合治疗的兴趣日益增加。然而，除了特定的适应证外，临床上的联合治疗通常不是系统地进行；相反，它是根据医生的判断作为一种避险机制使用，以增加用未知抗生素耐药谱的药物靶向病原体的机会。一些最近的临床试验未能证明联合治疗比单药治疗更有效。其他试验表明，在某些情况下联合治疗是有益的，这与最近的研究一致，这些研究表明包括物种、菌株、耐药谱和微环境在内的因素会影响药物联合的疗效和药物相互作用。在这篇综述中，我们讨论了如何通过仔细的研究设计来考虑这些因素，以及评估联合治疗效果的不同药物相互作用和效价指标，从而为理解联合治疗的最佳临床应用提供必要的见解。
