Theory to the rescue? Assessing the effect of antibiotic mode of action and concentration on resistance evolution

Pete Czuppon

Institute for Evolution and Biodiversity, University of Münster, Germany

p.czuppon@uni-muenster.de

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Link to online seminar: https://umontpellier-fr.zoom.us/webinar/register/WN_BqY7svsBTVecFb67ZG4ahA

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The use of an antibiotic creates a favorable environment for the evolution of resistant bacteria. The dosage of the antibiotic drug plays an important role during this process. Previous studies have shown that the optimal dose to limit resistance evolution will either be the highest or the lowest drug concentration possible to administer; however, no results exist that help decide between these two extremes. We developed a stochastic model of bacterial population dynamics under antibiotic treatment to address this gap. We explored various scenarios of density regulation (bacterial density affects birth or death rates), and antibiotic modes of action (biostatic or biocidal). Importantly, we obtain a prediction of the antibiotic concentration that maximizes the survival probability of resistant cells until the end of antibiotic treatment, which may help to decide which drug dosage (not) to administer. More generally, the modeling framework could be extended to scenarios of evolutionary rescue in ecological contexts.

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