The ecological and evolutionary mechanisms of antimicrobial resistance (AMR) emergence within patients and how these vary across bacterial infections are poorly understood. Increasingly widespread use of pathogen genome sequencing in the clinic enables a deeper understanding of these processes. In this Review, we explore the clinical evidence to support four major mechanisms of within-patient AMR emergence in bacteria: spontaneous resistance mutations; in situ horizontal gene transfer of resistance genes; selection of pre-existing resistance; and immigration of resistant lineages. Within-patient AMR emergence occurs across a wide range of host niches and bacterial species, but the importance of each mechanism varies between bacterial species and infection sites within the body. We identify potential drivers of such differences and discuss how ecological and evolutionary analysis could be embedded within clinical trials of antimicrobials, which are powerful but underused tools for understanding why these mechanisms vary between pathogens, infections and individuals. Ultimately, improving understanding of how host niche, bacterial species and antibiotic mode of action combine to govern the ecological and evolutionary mechanism of AMR emergence in patients will enable more predictive and personalized diagnosis and antimicrobial therapies.

人们对患者体内抗菌素耐药性 (AMR) 出现的生态和进化机制以及这些机制如何因细菌感染而变化的情况知之甚少。病原体基因组测序在临床中的日益广泛使用使得人们能够更深入地了解这些过程。在这篇综述中，我们探讨了支持患者体内细菌出现 AMR 的四种主要机制的临床证据：自发耐药突变；抗性基因的原位水平基因转移；选择已有的抵抗力；和抵抗谱系的移民。患者体内抗菌素耐药性的出现发生在广泛的宿主生态位和细菌种类中，但每种机制的重要性因细菌种类和体内感染部位而异。我们确定了这种差异的潜在驱动因素，并讨论了如何将生态和进化分析嵌入到抗菌药物的临床试验中，这些分析是强大但未得到充分利用的工具，可用于理解为什么这些机制在病原体、感染和个体之间存在差异。最终，加深对宿主生态位、细菌种类和抗生素作用模式如何结合起来控制患者 AMR 出现的生态和进化机制的理解，将使诊断和抗菌治疗更具预测性和个性化。