Minimizing treatment-induced emergence of antibiotic resistance in bacterial infections

Science. 2022 Feb 25;375(6583):889-894. doi: 10.1126/science.abg9868. Epub 2022 Feb 24.

Abstract

Treatment of bacterial infections currently focuses on choosing an antibiotic that matches a pathogen's susceptibility, with less attention paid to the risk that even susceptibility-matched treatments can fail as a result of resistance emerging in response to treatment. Combining whole-genome sequencing of 1113 pre- and posttreatment bacterial isolates with machine-learning analysis of 140,349 urinary tract infections and 7365 wound infections, we found that treatment-induced emergence of resistance could be predicted and minimized at the individual-patient level. Emergence of resistance was common and driven not by de novo resistance evolution but by rapid reinfection with a different strain resistant to the prescribed antibiotic. As most infections are seeded from a patient's own microbiota, these resistance-gaining recurrences can be predicted using the patient's past infection history and minimized by machine learning-personalized antibiotic recommendations, offering a means to reduce the emergence and spread of resistant pathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / microbiology*
  • Drug Resistance, Bacterial*
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / microbiology
  • Female
  • Humans
  • Machine Learning
  • Male
  • Microbial Sensitivity Tests
  • Microbiota
  • Mutation
  • Reinfection / microbiology*
  • Urinary Tract Infections / drug therapy
  • Urinary Tract Infections / microbiology
  • Whole Genome Sequencing
  • Wound Infection / drug therapy
  • Wound Infection / microbiology

Substances

  • Anti-Bacterial Agents