Direct antimicrobial resistance prediction from clinical MALDI-TOF mass spectra using machine learning

Nat Med. 2022 Jan;28(1):164-174. doi: 10.1038/s41591-021-01619-9. Epub 2022 Jan 10.


Early use of effective antimicrobial treatments is critical for the outcome of infections and the prevention of treatment resistance. Antimicrobial resistance testing enables the selection of optimal antibiotic treatments, but current culture-based techniques can take up to 72 hours to generate results. We have developed a novel machine learning approach to predict antimicrobial resistance directly from matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectra profiles of clinical isolates. We trained calibrated classifiers on a newly created publicly available database of mass spectra profiles from the clinically most relevant isolates with linked antimicrobial susceptibility phenotypes. This dataset combines more than 300,000 mass spectra with more than 750,000 antimicrobial resistance phenotypes from four medical institutions. Validation on a panel of clinically important pathogens, including Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae, resulting in areas under the receiver operating characteristic curve of 0.80, 0.74 and 0.74, respectively, demonstrated the potential of using machine learning to substantially accelerate antimicrobial resistance determination and change of clinical management. Furthermore, a retrospective clinical case study of 63 patients found that implementing this approach would have changed the clinical treatment in nine cases, which would have been beneficial in eight cases (89%). MALDI-TOF mass spectra-based machine learning may thus be an important new tool for treatment optimization and antibiotic stewardship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Drug Resistance, Microbial*
  • Escherichia coli / drug effects
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Machine Learning*
  • Microbial Sensitivity Tests
  • Retrospective Studies
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Staphylococcus aureus / drug effects


  • Anti-Bacterial Agents

Associated data

  • Dryad/10.5061/dryad.bzkh1899q