Linking within- and between-host scales for understanding the evolutionary dynamics of quantitative antimicrobial resistance

Understanding both the epidemiological and evolutionary dynamics of antimicrobial resistance is a major public health concern. In this paper, we propose a nested model, explicitly linking the within- and between-host scales, in which the level of resistance of the bacterial population is viewed as a continuous quantitative trait. The within-host dynamics is based on integro-differential equations structured by the resistance level, while the between-host scale is additionally structured by the time since infection. This model simultaneously captures the dynamics of the bacteria population, the evolutionary transient dynamics which lead to the emergence of resistance, and the epidemic dynamics of the host population. Moreover, we precisely analyze the model proposed by particularly performing the uniform persistence and global asymptotic results. Finally, we discuss the impact of the treatment rate of the host population in controlling both the epidemic outbreak and the average level of resistance, either if the within-host scale therapy is a success or failure. We also explore how transitions between infected populations (treated and untreated) can impact the average level of resistance, particularly in a scenario where the treatment is successful at the within-host scale.