Antibiotic resistance is a worldwide and growing clinical problem. With limited drug development in the antibacterial space, combination therapy has emerged as a promising strategy to combat multidrug-resistant bacteria. Antibacterial combinations can improve antibiotic efficacy and suppress antibacterial resistance through independent, synergistic, or even antagonistic activities. Combination therapies are famously used to treat viral and mycobacterial infections and cancer. However, antibacterial combinations are only now emerging as a common treatment strategy for other bacterial infections owing to challenges in their discovery, development, regulatory approval, and commercial/clinical deployment. Here, we focus on discovery—where the sheer scale of combinatorial chemical spaces represents a significant challenge—and discuss how combination therapy can impact the treatment of bacterial infections. Despite these challenges, recent advancements, including new in silico methods, theoretical frameworks, and microfluidic platforms, are poised to identify the new and efficacious antibacterial combinations needed to revitalize the antibacterial drug pipeline.

中文翻译：

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抗生素的未来始于发现新组合

抗生素耐药性是一个全球性且日益严重的临床问题。由于抗菌领域的药物开发有限，联合疗法已成为对抗多重耐药细菌的有希望的策略。抗菌组合可以通过独立的、协同的甚至拮抗的活性来提高抗生素的疗效并抑制抗菌素的耐药性。联合疗法以治疗病毒和分枝杆菌感染以及癌症而闻名。然而，由于在发现、开发、监管批准和商业/临床部署方面存在挑战，抗菌组合现在才成为其他细菌感染的常见治疗策略。这里，我们专注于发现——组合化学空间的庞大规模代表着重大挑战——并讨论联合疗法如何影响细菌感染的治疗。尽管存在这些挑战，但最近的进展，包括新的计算机方法、理论框架和微流控平台有望确定振兴抗菌药物管道所需的新的有效抗菌组合。