Department of Biochemistry and Biomedical Sciences, M.G. DeGroote Institute for Infectious Disease Research, McMaster University Hamilton, ON, Canada.
Expert Rev Mol Med. 2011 Feb 23;13:e5. doi: 10.1017/S1462399410001766.
The unremitting emergence of multidrug-resistant bacterial pathogens highlights a matching need for new therapeutic options. For example, new carbapenemases such as KPC (class A Klebsiella pneumoniae) and NDM-1 (New Delhi metallo-β-lactamase 1) are surfacing, resulting in almost total resistance to β-lactam antibiotics. Furthermore, resistance is quickly disseminated, not only in the healthcare sector, but also within the community at large, because many resistance determinants are carried on mobile genetic elements readily shared among pathogens. The absence of new antibiotics has led to a growing reliance on older, more toxic drugs such as colistin, but resistance to these is already arising. One approach to combat this growing problem is the use of combination drug antibiotic adjuvant therapy, which potentiates the activity of antibiotics. Here, we review the current situation and discuss potential drug combinations that may increase the potency of antibiotics in the future. Adjuvant therapies include antibiotic combinations, synergy between antibiotics and nonantibiotics, inhibition of resistance and molecules that alter the physiology of antibiotic-insensitive cells, such as those in biofilms. We provide a rationale for these multicomponent strategies, highlighting current research and important considerations for their clinical use and pharmacological properties.
不断出现的多药耐药细菌病原体凸显了对新治疗选择的相应需求。例如，新的碳青霉烯酶，如 KPC（A 类肺炎克雷伯菌）和 NDM-1（新德里金属β-内酰胺酶 1）正在出现，导致对β-内酰胺类抗生素几乎完全耐药。此外，耐药性迅速传播，不仅在医疗保健部门，而且在整个社区，因为许多耐药决定因素都存在于移动遗传元件上，这些元件很容易在病原体之间共享。缺乏新的抗生素导致人们越来越依赖于更老、毒性更大的药物，如黏菌素，但这些药物的耐药性已经出现。对抗这一日益严重问题的一种方法是使用联合药物抗生素佐剂疗法，这种疗法可以增强抗生素的活性。在这里，我们回顾了当前的情况，并讨论了未来可能增加抗生素效力的潜在药物组合。佐剂疗法包括抗生素组合、抗生素与非抗生素之间的协同作用、抑制耐药性以及改变抗生素不敏感细胞生理的分子，如生物膜中的细胞。我们为这些多组分策略提供了一个基本原理，强调了当前的研究以及它们在临床应用和药理学特性方面的重要考虑因素。
