PT  - JOURNAL ARTICLE
AU  - Nicholas G. Davies
AU  - Stefan Flasche
AU  - Mark Jit
AU  - Katherine E. Atkins
TI  - Within-host dynamics explain the coexistence of antibiotic-sensitive and resistant bacteria
AID  - 10.1101/217232
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 217232
4099  - http://biorxiv.org/content/early/2017/11/10/217232.short
4100  - http://biorxiv.org/content/early/2017/11/10/217232.full
AB  - Antibiotic resistance is one of the foremost threats to human health1,2, yet the spread of resistance is poorly understood. Resistant and sensitive strains of the same bacteria nearly always coexist in host populations3-5, but mathematical models of disease transmission have failed to identify a general, empirically-supported mechanism that can reproduce this phenomenon6–9. Such a model should be structurally neutral10, meaning that coexistence arises from the biology of sensitive and resistant strains rather than being an assumption embedded into the model structure. However, existing models have only applied the principle of structural neutrality at the population level, not within individual hosts where resistant and sensitive strains may interact. Here, we show that within-host dynamics between resistant and sensitive strains creates frequency-dependent selection for resistance, promoting coexistence at the population level, and that extending structural neutrality to the within-host level allows us to reproduce empirical patterns of resistance in commensal bacteria across 30 European countries. In doing so, we identify a parsimonious and biologically-plausible explanation for coexistence that resolves a long-standing conflict between theoretical prediction and empirical observation. Simple mathematical models that mechanistically capture resistance transmission dynamics will allow us to more accurately predict the impact of much-needed strategies for managing resistance.