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. Access through your institution Buy or subscribe This is a

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RESISTANCE EVOLUTION Article Open access 07 September 2023 EVOLUTIONARY ACTION OF MUTATIONS REVEALS ANTIMICROBIAL RESISTANCE GENES IN ESCHERICHIA COLI Article Open access 09 June 2022

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_Nat. Rev. Drug. Discov._ 12, 371–387 (2013). Article  CAS  PubMed  Google Scholar  Download references 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.). AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * 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 * and at The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby DK-2800, Denmark., Morten O. A. Sommer * Christian

Munck is at The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby DK-2800, Denmark., Christian Munck * AntibioTx A/S, Kemitorvet, Lyngby, DK-2800,

Denmark Rasmus Vendler Toft-Kehler * Department of Medical Biochemistry and Microbiology, Uppsala University, Husargatan 3, Uppsala, SE-751 23, Sweden Dan I. Andersson Authors * Morten O.

A. Sommer View author publications You can also search for this author inPubMed Google Scholar * Christian Munck View author publications You can also search for this author inPubMed Google

Scholar * Rasmus Vendler Toft-Kehler View author publications You can also search for this author inPubMed Google Scholar * Dan I. Andersson View author publications You can also search for

this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Dan I. Andersson. ETHICS DECLARATIONS COMPETING INTERESTS 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. POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1

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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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