Singh Nina, Yeh Pamela J
Department of Ecology and Evolutionary Biology, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
J Antibiot (Tokyo). 2017 Nov;70(11):1033-1042. doi: 10.1038/ja.2017.102. Epub 2017 Sep 6.
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.
当同时使用两种或更多种此类药物时，抗生素的有效性常常会发生变化，发掘具有增强疗效（协同作用）的抗生素组合一直是一个长期的临床目标。然而，破坏单一药物疗效的抗生素耐药性对这种联合治疗构成了威胁。值得注意的是，已经发现联合效应低于至少一种单一药物的抗生素组合可以减缓甚至逆转耐药性的演变。我们综合并回顾了文献中关于此类所谓“抑制性相互作用”的研究。我们探讨了为什么这些相互作用在过去基本上被忽视，用于识别它们的策略，它们的机制基础，证明它们具有逆转耐药性演变的潜力以及支持和反对在临床治疗中使用它们的论据。我们提出了关于这些相互作用的未来研究方向，旨在扩大关于抑制作用的基础知识体系，并确定抑制性相互作用在临床中的适用性。
