Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings.

阳离子抗菌肽（AMPs）是人类先天免疫系统的固有组成部分。已知超过100种不同的人AMP具有广谱抗菌活性。由于对常规抗生素的抗性频率增加，因此有兴趣开发AMPs作为一种替代的抗菌疗法。来自人类先天免疫系统的AMP衍生物的几种阳离子肽目前正在临床开发中。也有正在进行的临床研究旨在调节AMPs的表达以增强人类先天免疫反应。在这篇综述中，我们讨论了与这些治疗方法有关的潜在问题。有大量实验数据描述了细菌对AMPs产生抗性的机制。至于任何类型的耐药性，在自然环境中，AMP抗药性在细菌种群中出现和扩散的速率将取决于多种不同因素的复杂相互作用，其中包括突变提供率，抗药性突变株在不同AMP浓度下的适应性以及选择压力的强度。几项研究已经表明，抗AMP的细菌突变体对具有不同结构和作用方式的各种AMP表现出广泛的交叉耐药性。因此，用于治疗细菌感染的AMP的常规临床给药可以选择能够更好地逃避先天免疫系统的耐药细菌病原体。尚不了解治疗水平的暴露对AMP耐药性发展和细菌发病机理的影响。