Rethinking our approach to managing the evolution of drug resistance

Abstract

The evolution of antimicrobial resistant pathogens threatens much of modern medicine. For over one hundred years, the advice has been to `hit hard', in the belief that high doses of antimicrobials best contain resistance evolution. In this talk I will argue that nothing in evolutionary theory supports this as a good rule of thumb. To illustrate my argument I will present a simple model showing how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. Moreover, I suggest that a vast body of experimental and observational data provides broad support for this general conclusion. Finally, I will show how these theoretical results point to a novel strategy for controlling resistance, and I will show some preliminary experimental data aimed at testing this idea.