TY - JOUR T1 - Population structure across scales facilitates coexistence and spatial heterogeneity of antibiotic-resistant infections JF - bioRxiv DO - 10.1101/469171 SP - 469171 AU - Madison S. Krieger AU - Carson E. Denison AU - Thayer L. Anderson AU - Martin A. Nowak AU - Alison L. Hill Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/06/24/469171.abstract N2 - Antibiotic-resistant infections are a growing threat to human health, but basic features of the eco-evolutionary dynamics remain unexplained. Most prominently, there is no clear mechanism for the long-term coexistence of both drug-sensitive and resistant strains at intermediate levels, a ubiquitous pattern seen in surveillance data. Here we show that accounting for structured or spatially-heterogeneous host populations and variability in antibiotic consumption can lead to persistent coexistence over a wide range of treatment coverages, drug efficacies, costs of resistance, and mixing patterns. Moreover, this mechanism can explain other puzzling spatiotemporal features of drug-resistance epidemiology that have received less attention, such as large differences in the prevalence of resistance between geographical regions with similar antibiotic consumption or that neighbor one another. We find that the same amount of antibiotic use can lead to very different levels of resistance depending on how treatment is distributed in a transmission network. We also identify parameter regimes in which population structure alone cannot support coexistence, suggesting the need for other mechanisms to explain the epidemiology of antibiotic resistance. Our analysis identifies key features of host population structure that can be used to assess resistance risk and highlights the need to include spatial or demographic heterogeneity in models to guide resistance management.Competing Interest StatementThe authors have declared no competing interest. ER -