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bioRxiv · 10.1101/217232

Within-host dynamics explain the coexistence of antibiotic-sensitive and resistant bacteria

Davies, N. G.·Flasche, S.·Jit, M.·Atkins, K. E.
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Abstract

The spread of antibiotic resistance, a major threat to human health, is poorly understood. Empirically, resistant strains gradually increase in prevalence as antibiotic consumption increases, but current mathematical models predict a sharp transition between full sensitivity and full resistance. In other words, we do not understand what drives persistent coexistence between resistant and sensitive strains of disease-causing bacteria in host populations. Without knowing what drives patterns of resistance, we cannot accurately predict the impact of potential strategies for managing resistance. Here, we show that within-host dynamics--bacterial growth, strain competition, and host immune responses--promote frequency-dependent selection for resistant strains, explaining patterns of resistance at the population level. By capturing these processes in a parsimonious mathematical framework, we resolve a long-standing conflict between theory and observation. Our models capture widespread coexistence for multiple bacteria-drug combinations across 30 European countries and explain associations between carriage prevalence and resistance prevalence among bacterial subtypes. A mechanistic understanding of resistance evolution is needed to accurately forecast the impact and effectiveness of resistance-management strategies.

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Davies, N. G., Flasche, S., Jit, M., Atkins, K. E.. 2017-11-10. Within-host dynamics explain the coexistence of antibiotic-sensitive and resistant bacteria. https://doi.org/10.1101/217232

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