Interactions within higher-order antibiotic combinations do not influence the rate of adaptation in bacteria.

The prevalence and strength of antibiotic resistance has led to an ongoing battle between the development of new treatments and the evolution of resistance. Combining multiple drugs simultaneously is a potential solution for combating antibiotic resistance. However, this approach introduces new factors that must be considered, including the influence of drug interactions on the rate of resistance evolution. When antibiotics are used in combination, their effects can be additive, synergistic, or antagonistic. In this study, we investigated the effect of higher-order interactions involving three drugs on resistance evolution in Staphylococcus epidermidis. Previous studies have shown that synergistic interactions can increase the adaptation rate. However, the effects of higher-order interactions on rates of adaptation are unclear. We investigated the adaptation of Staphylococcus epidermidis to single-, two-, and three-drug environments to assess how interactions within drug combinations influence the rate of adaptation. We analyzed both the overall interaction and emergent interaction, the latter being a unique interaction that occurs in three-drug combinations due to the presence of all three drugs, rather than simply strong pairwise interactions. Our results show that neither the overall interactions nor the emergent interactions affect adaptation rates.

抗生素耐药性的传播与强化，使得新疗法研发与耐药性演化之间的博弈持续进行。联合使用多种药物是对抗抗生素耐药性的潜在策略，但该方法同时引入了诸多需考量的新因素，其中包括药物相互作用对耐药性演化速率的影响。抗生素联合给药时，其药效可呈现相加、协同或拮抗三种模式。
本研究以表皮葡萄球菌（Staphylococcus epidermidis）为研究对象，探究了包含三种药物的高阶相互作用（higher-order interactions）对其耐药性演化的影响。已有研究证实，协同相互作用可提升菌株的适应速率，但高阶相互作用对适应速率的影响仍不明朗。为明确药物组合内的相互作用如何影响适应速率，我们分析了表皮葡萄球菌在单药、双药及三药培养环境中的适应情况。我们同时分析了整体相互作用与涌现相互作用：其中涌现相互作用是仅在三药组合中因三种药物同时存在而产生的独特相互作用，而非单纯的强两两相互作用。本研究结果显示，无论是整体相互作用还是涌现相互作用，均未对表皮葡萄球菌的适应速率产生显著影响。