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Prediction of antibiotic resistance: time for a new preclinical paradigm?

Nature Reviews Microbiology volume 15, pages 689–696 (2017)Cite this article

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Abstract

Predicting the future is difficult, especially for evolutionary processes that are influenced by numerous unknown factors. Still, this is what is required of drug developers when they assess the risk of resistance arising against a new antibiotic candidate during preclinical development. In this Opinion article, we argue that the traditional procedures that are used for the prediction of antibiotic resistance today could be markedly improved by including a broader analysis of bacterial fitness, infection dynamics, horizontal gene transfer and other factors. This will lead to more informed preclinical decisions for continuing or discontinuing the development of drug candidates.

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Figure 1: Evolution of resistance.
Figure 2: Factors that determine the risk of evolution of antibiotic resistance.
Figure 3: The in vitro rate of resistance mutations does not correlate with the burden of resistance in the clinic.
Figure 4: Examining the potential of horizontal gene transfer.

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Acknowledgements

Work in the authors' laboratories was supported by grants from the Swedish Research Council (to D.I.A.), and the Novo Nordisk Foundation, the Lundbeck Foundation and the Danish Free Research Council (to M.O.A.S. and C.M.).

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Authors and Affiliations

  1. AntibioTx A/S, Kemitorvet, Lyngby DK-2800, Denmark; and at The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby DK-2800, Denmark.,

    Morten O. A. Sommer

  2. and at The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby DK-2800, Denmark.,

    Morten O. A. Sommer

  3. Christian Munck is at The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby DK-2800, Denmark.,

    Christian Munck

  4. AntibioTx A/S, Kemitorvet, Lyngby, DK-2800, Denmark

    Rasmus Vendler Toft-Kehler

  5. Department of Medical Biochemistry and Microbiology, Uppsala University, Husargatan 3, Uppsala, SE-751 23, Sweden

    Dan I. Andersson

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Correspondence to Dan I. Andersson.

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The authors declare the following competing interests: M.O.A.S. and R.T.K. are shareholders in AntibioTx; C.M. declares no competing interests; D.I.A. is a consultant for Prebona and Bactiguard.

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Sommer, M., Munck, C., Toft-Kehler, R. et al. Prediction of antibiotic resistance: time for a new preclinical paradigm?. Nat Rev Microbiol 15, 689–696 (2017). https://doi.org/10.1038/nrmicro.2017.75

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