Design principles of collateral sensitivity-based dosing strategies
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Collateral sensitivity (CS)-based antibiotic treatments, where increased resistance to one antibiotic leads to increased sensitivity to a second antibiotic, may have the potential to limit the emergence of antimicrobial resistance. However, it remains unclear how to best design CS-based treatment schedules. To address this problem, we use mathematical modelling to study the effects of pathogen- and drug-specific characteristics for different treatment designs on bacterial population dynamics and resistance evolution. We confirm that simultaneous and one-day cycling treatments could supress resistance in the presence of CS. We show that the efficacy of CS-based cycling therapies depends critically on the order of drug administration. Finally, we find that reciprocal CS is not essential to suppress resistance, a result that significantly broadens treatment options given the ubiquity of one-way CS in pathogens. Overall, our analyses identify key design principles of CS-based treatment strategies and provide guidance to develop treatment schedules to suppress resistance.
Authors 5
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Affiliation as printed
Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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Affiliation as printed
Institute of Biology, Leiden University, Leiden, The Netherlands
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Affiliation as printed
Certara, Canterburry, United Kingdom
Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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Affiliation as printed
Institute of Biology, Leiden University, Leiden, The Netherlands
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Affiliation as printed
Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
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