Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

ABSTRACT: High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose li

SUBMITTER: Day T 

PROVIDER: S-EPMC4731197 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature