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Design principles of collateral sensitivity-based dosing strategies

Author

Listed:
  • Linda B. S. Aulin

    (Leiden University)

  • Apostolos Liakopoulos

    (Leiden University)

  • Piet H. Graaf

    (Leiden University
    Certara)

  • Daniel E. Rozen

    (Leiden University)

  • J. G. Coen van Hasselt

    (Leiden University)

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.

Suggested Citation

  • Linda B. S. Aulin & Apostolos Liakopoulos & Piet H. Graaf & Daniel E. Rozen & J. G. Coen van Hasselt, 2021. "Design principles of collateral sensitivity-based dosing strategies," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25927-3
    DOI: 10.1038/s41467-021-25927-3
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    Cited by:

    1. Natalie J. E. Waller & Chen-Yi Cheung & Gregory M. Cook & Matthew B. McNeil, 2023. "The evolution of antibiotic resistance is associated with collateral drug phenotypes in Mycobacterium tuberculosis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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