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Suppressive drug combinations and their potential to combat antibiotic resistance.
The Journal of Antibiotics ( IF 3.3 ) Pub Date : 2017-Nov-01 , DOI: 10.1038/ja.2017.102
Nina Singh , Pamela J Yeh

Antibiotic effectiveness often changes when two or more such drugs are administered simultaneously and unearthing antibiotic combinations with enhanced efficacy (synergy) has been a longstanding clinical goal. However, antibiotic resistance, which undermines individual drugs, threatens such combined treatments. Remarkably, it has emerged that antibiotic combinations whose combined effect is lower than that of at least one of the individual drugs can slow or even reverse the evolution of resistance. We synthesize and review studies of such so-called 'suppressive interactions' in the literature. We examine why these interactions have been largely disregarded in the past, the strategies used to identify them, their mechanistic basis, demonstrations of their potential to reverse the evolution of resistance and arguments for and against using them in clinical treatment. We suggest future directions for research on these interactions, aiming to expand the basic body of knowledge on suppression and to determine the applicability of suppressive interactions in the clinic.

中文翻译:

抑制性药物组合及其对抗抗生素耐药性的潜力。

当同时施用两种或多种此类药物时,抗生素效力通常会发生变化,并且挖掘出具有增强功效(协同作用)的抗生素组合已成为长期的临床目标。但是,破坏单个药物的抗生素耐药性威胁着这种联合治疗。值得注意的是,已经发现,其联合作用比至少一种单独药物的联合作用低的抗生素组合可以减缓甚至逆转耐药性的发展。我们对文献中所谓的“抑制性相互作用”进行了综合和综述。我们将研究为什么这些互动过去在很大程度上已被忽略,用于识别它们的策略,它们的机理基础,证明它们具有逆转耐药性演变的潜力,并支持在临床治疗中使用和反对使用它们。我们为这些相互作用的研究提出了未来的方向,旨在扩大抑制的基本知识,并确定抑制性相互作用在临床中的适用性。
更新日期:2017-09-06
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