Abstract

The evolution of antibiotic resistance in opportunistic pathogens such as Streptococcus pneumoniae, Escherichia coli or Staphylococcus aureus is a major public health problem, as infection with resistant strains leads to prolonged hospital stay and increased risk of death. Here, we develop a new model of the evolution of antibiotic resistance in a commensal bacterial population adapting to a heterogeneous host population composed of untreated and treated hosts, and structured in different host classes with different antibiotic use. Examples of host classes include age groups and geographic locations. Explicitly modelling the antibiotic treatment reveals that the emergence of a resistant strain is favoured by more frequent but shorter antibiotic courses, and by higher transmission rates. In addition, in a structured host population, localized transmission in host classes promotes both local adaptation of the bacterial population and the global maintenance of coexistence between sensitive and resistant strains. When transmission rates are heterogeneous across host classes, resistant strains evolve more readily in core groups of transmission. These findings have implications for the better management of antibiotic resistance: reducing the rate at which individuals receive antibiotics is more effective to reduce resistance than reducing the duration of treatment. Reducing the rate of treatment in a targeted class of the host population allows greater reduction in resistance, but determining which class to target is difficult in practice.

Highlights

  • The evolution of antimicrobial resistance in bacteria is an important public health problem [1], as infection with resistant strains leads to prolonged hospital stay and increased risk of death [2,3,4,5,6]

  • We model the evolution of antibiotic resistance in a host population divided into several classes using a compartmental ordinary differential equation (ODE) model

  • We developed a model of the evolution of antibiotic resistance in a structured population, where the host population is subdivided into different classes using antibiotics at different rates

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Summary

Introduction

The evolution of antimicrobial resistance in bacteria is an important public health problem [1], as infection with resistant strains leads to prolonged hospital stay and increased risk of death [2,3,4,5,6]. Multiple genotypes resistant to antibiotics have emerged worldwide in past years in these mainly commensal species, and the frequency of most types of resistance has stabilized at an intermediate level. In S. pneumoniae, resistance is associated with globally distributed clones [9,10,11,12], has remained stable in the USA and in Europe over the last 15–20 years [13,14,15] and correlates with levels of antibiotic use across countries [16], suggesting that antibiotics exert strong selection favouring resistant strains. It may seem intuitive that resistance has evolved because of antibiotic use, the stable equilibrium of resistance at an intermediate level, observed for several types of resistance in several species, is surprising. Models show that depending on the balance between the rate of treatment and the cost of resistance, the resistant

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