Interplay between strain fitness and transmission frequency determines prevalence of antimicrobial resistance

The steep rise of infections caused by bacteria that are resistant to antimicrobial agents threatens global health. However, the association between antimicrobial use and the prevalence of resistance is not straightforward. Therefore, it is necessary to quantify the importance of additional factors that affect this relationship. We theoretically explore how the prevalence of resistance is affected by the combination of three factors: antimicrobial use, bacterial transmission, and fitness cost of resistance. We present a model that combines within-host, between-hosts and between-populations dynamics, built upon the competitive Lotka-Volterra equations. We developed the model in a manner that allows future experimental validation of the findings with single isolates in the laboratory. Each host may carry two strains (susceptible and resistant) that represent the host's commensal microbiome and are not the target of the antimicrobial treatment. The model simulates a population of hosts who are treated periodically with antibiotics and transmit bacteria to each other. We show that bacterial transmission results in strain co-existence. Transmission disseminates resistant bacteria in the population, increasing the levels of resistance. Counterintuitively, when the cost of resistance is low, high transmission frequencies reduce resistance prevalence. Transmission between host populations leads to more similar resistance levels, increasing the susceptibility of the population with higher antimicrobial use. Overall, our results indicate that the interplay between bacterial transmission and strain fitness affects the prevalence of resistance in a non-linear way. We then place our results within the context of ecological theory, particularly on temporal niche partitioning and metapopulation rescue, and we formulate testable experimental predictions for future research.