Abstract
Rapid and accurate antimicrobial susceptibility testing (AST) is critical for guiding therapy in life-threatening infections such as sepsis, but current diagnostics rely on blood culture, delaying results by 48–72 h. This time lag forces empirical use of broad-spectrum antibiotics, increasing risks of treatment failure and antimicrobial resistance. We developed an approach combining bacterial growth-independent nanomotion detection with magnetic bead–based enrichment directly from blood. Using machine-learning classifiers trained on nanomotion spectra, we established ten antibiotic-specific models across 1,337 blood culture samples containing 390 clinical isolates of Enterobacterales (e.g., Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae) and Pseudomonas aeruginosa. These models achieved 94–98% sensitivity and specificity with fixed 2-h readouts. In parallel, SepsiSTAT enrichment enabled rapid recovery of viable bacteria and yeast at clinically relevant concentrations from 10 mL blood, with time-to-positivity averaging 5.5 h, i.e., over 7 h faster and more predictable than conventional blood culturing. The workflow was afterwards adapted to 1 mL input volumes, compatible with blood volume sampling constraints in fragile patient groups such as geriatric or neonatal patients. In spiked E. coli blood samples, ceftriaxone susceptibility was determined within 9–11 h of collection, nearly two days earlier than current standards. By integrating enrichment with nanomotion AST, we introduce a low-volume, label-free, phenotypic diagnostic platform capable of delivering actionable results within clinically meaningful timeframes. This approach holds potential to improve antibiotic stewardship, enable earlier transition from empiric to targeted therapy, and expand diagnostic access for vulnerable populations such as neonates.
Data availability
Link to code: https://github.com/resistell-com/neur-ast-2h.git.
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Acknowledgements
We gratefully acknowledge all institutions and collaborators who provided bacterial isolates and contributed to this study. These include Dr Stephen Hawser from the International Health Management Associates (IHMA); Shionogi & Co., Ltd.; Pfizer Inc.; Dr. Patrice Nordmann and colleagues at the Swiss Centre for Emerging Antibiotic Resistances (NARA); Helmholtz Centre for Infection Research; Prof. Dirk Bumann and Ms. Beatrice Claudi from the Biozentrum, University of Basel; Hvidovre Hospital, Denmark; Centre Hospitalier Universitaire Vaudois (CHUV), Switzerland; Hospital Universitario Ramón y Cajal, Spain; the Centers for Disease Control and Prevention (CDC), USA; Mr. Christian Miscenic from F. Hoffmann-La Roche Ltd.; Dr. Michael Oberle and Ms. Nadine Hunn from the Kantonsspital Aarau, Switzerland; Prof. Cornelia Lass-Floerl and Dr. Ronald Gstir from the University Hospital Innsbruck, Austria; and the American Type Culture Collection (ATCC). We thank them for their generous contributions of clinical and reference strains. We thank Prof. Sandor Kasas for the discussion and all contributors of the JPIAMR ERADIAMR consortiums for their valuable inputs. We also thank Mr. Grzegorz Gonciarz for his support and Mr. Piotr Grzywacz for graphical design support.
Funding
G.G., R.C., S.H., T.T., and S.P. were partially funded by the national funding bodies within JPIAMR-Development of innovative strategies, tools, technologies, and methods for diagnostics and surveillance of antimicrobial resistance.
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D.C., D.L., and A.S. were responsible for the project’s conception and design. M.P.V., A.L.E., C.M., E.M., D.W.O., S.L.F., M.G.C., E.D., K.F., L.M., C.V., D.B., and S.R. conducted experiments. G.J. and G.C. developed the nanomotion AST classification algorithms. Data analysis was performed by G.J., A.S., D.L., M.P.V., and G.C.; M.S. and R.T. were responsible for the technical development of the Phenotech devices. A.S., D.L., D.C., G.J., M.S., E.S., R.C., G.G., G.L., W.M., T.T., S.H., and S.P. wrote/edited the manuscript and provided resources. Supplementary Information and Supplementary Data 1 and 2 were compiled by A.S. and G.J.
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G.L. serves as a scientific advisor to Momentum Bioscience. R.C. and G.G. serve as scientific advisors to Resistell. E.D., A.L.E., M.S., and are inventors on a patent application (PCT/EP2020/08782) filed by Resistell concerning bacterial attachment to a cantilever. G.J., A.S., E.D., and D.C. are inventors on another Resistell patent application (PCT/EP2023/055596) related to machine learning analysis of particle motion on a cantilever. Resistell also holds an exclusive license for the patent EP2766722B1, which protects a nanoscale motion detector.
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Jóźwiak, G., Pla Verge, M., Luraschi-Eggemann, A. et al. Nanomotion-enabled ultra-rapid antibiotic susceptibility testing with magnetic bead-based pathogen enrichment for accelerated sepsis diagnostics. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44519-z
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DOI: https://doi.org/10.1038/s41598-026-44519-z