How competition governs whether moderate or aggressive treatment minimizes antibiotic resistance

Abstract

The growing burden of antimicrobial resistance is one of the most challenging problems facing public health today, and understanding how our approaches for using antimicrobial drugs shapes future levels of resistance is crucial. Recently there has been debate over whether an aggressive (i.e. high dose) or more moderate (i.e. lower dose) treatment of individuals will most limit the emergence and spread of resistant bacteria. Here we demonstrate how one can understand and resolve these apparently contradictory conclusions. We show that a key determinant of which treatment strategy will perform best at the individual level is the extent of effective competition between resistant and sensitive pathogens within a host. We extend our analysis to the community level, exploring the spectrum between strict inter-strain competition and strain independence. From this perspective as well, we find that the magnitude of effective competition between resistant and sensitive strains determines whether an aggressive approach or moderate approach minimizes the burden of resistance in the population.