Design principles of collateral sensitivity-based dosing strategies

Aulin, L. B. S.; Liakopoulos, A.; van der Graaf, P. H.; Rozen, D. E.; van Hasselt, J. G. C.

doi:10.1101/2021.03.31.437927

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bioRxiv · 10.1101/2021.03.31.437927

Design principles of collateral sensitivity-based dosing strategies

Aulin, L. B. S.·Liakopoulos, A.·van der Graaf, P. H.·Rozen, D. E.·van Hasselt, J. G. C.

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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.

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Aulin, L. B. S., Liakopoulos, A., van der Graaf, P. H., Rozen, D. E., van Hasselt, J. G. C.. 2021-03-31. Design principles of collateral sensitivity-based dosing strategies. https://doi.org/10.1101/2021.03.31.437927

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