Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Department of Internal Medicine, Division of Infectious Diseases, University of Michigan, Ann Arbor, Michigan, USA.
mSphere. 2024 Aug 28;9(8):e0041724. doi: 10.1128/msphere.00417-24. Epub 2024 Aug 2.
Although antibiotics remain a cornerstone of modern medicine, the issues of widespread antibiotic resistance and collateral damage to the microbiome from antibiotic use are driving a need for drug developers to consider more tailored, patient-directed products to avoid antibiotic-induced perturbations of the structure and function of the indigenous microbiota. This perspective summarizes a cascade of microbiome health effects that is initiated by antibiotic-mediated microbiome disruption at an individual level and ultimately leads to infection and transmission of multidrug-resistant pathogens across patient populations. The scientific evidence behind each of the key steps of this cascade is presented. The interruption of this cascade through the use of highly targeted, microbiome-sparing antibiotics aiming to improve health outcomes is discussed. Further, this perspective reflects on some key clinical trial design and reimbursement considerations to be addressed as part of the drug development path.
虽然抗生素仍然是现代医学的基石，但抗生素的广泛耐药性问题以及抗生素使用对微生物组的附带损害，促使药物开发者考虑更具针对性、面向患者的产品，以避免抗生素引起的内源性微生物组结构和功能的紊乱。本观点总结了一个由抗生素介导的微生物组破坏在个体层面引发的一系列微生物组健康效应，最终导致多药耐药病原体在患者群体中的感染和传播。本文介绍了这一连锁反应中每一个关键步骤的科学依据。通过使用高度靶向、保护微生物组的抗生素来打断这一连锁反应，从而改善健康结果，这一策略也在文中进行了讨论。此外，本观点还反映了一些关键的临床试验设计和报销考虑因素，这些都是药物开发过程中需要解决的问题。
