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Author Notes:

R.M.D. (dickson@chemistry.gatech.edu)

The authors declare no competing financial interests.

Subjects:

Research Funding:

The authors gratefully acknowledge support of these studies from the National Institutes of Health, Award number R01AI107116 and the Vasser-Woolley Foundation.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemical Research Methods
  • Cell Biology
  • Biochemistry & Molecular Biology
  • multidrug-resistant bacteria
  • antibiotic susceptibility test
  • flow cytometry
  • pre-blood culture
  • multidimensional statistics
  • BLOOD-STREAM INFECTIONS
  • ESCHERICHIA-COLI
  • FLOW-CYTOMETRY
  • BACTERIAL
  • IDENTIFICATION
  • RESISTANCE
  • OUTCOMES
  • ASSAY

FAST: Rapid determinations of antibiotic susceptibility phenotypes using label-free cytometry

Tools:

Journal Title:

Cytometry Part A

Volume:

Volume 93A, Number 6

Publisher:

, Pages 639-648

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Sepsis, a life-threatening immune response to blood infections (bacteremia), has a ∼30% mortality rate and is the 10th leading cause of US hospital deaths. The typical bacterial loads in adult septic patients are ≤100 bacterial cells (colony forming units, CFU) per ml blood, while pediatric patients exhibit only ∼1000 CFU/ml. Due to the low numbers, bacteria must be propagated through ∼24-hours blood cultures to generate sufficient CFUs for diagnosis and further analyses. Herein, we demonstrate that, unlike other rapid post-blood culture antibiotic susceptibility tests (ASTs), our phenotypic approach can drastically accelerate ASTs for the most common sepsis-causing gram-negative pathogens by circumventing long blood culture-based amplification. For all blood isolates of multi-drug resistant pathogens investigated (Escherichia coli, Klebsiella pneumoniae, and Acinetobacter nosocomialis), effective antibiotic(s) were readily identified within the equivalent of 8 hours from initial blood draw using <0.5 mL of adult blood per antibiotic. These methods should drastically improve patient outcomes by significantly reducing time to actionable treatment information and reduce the incidence of antibiotic resistance.

Copyright information:

© 2018 International Society for Advancement of Cytometry.

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