A rapid antimicrobial susceptibility test based on single-cell morphological analysis

Sci Transl Med. 2014 Dec 17;6(267):267ra174. doi: 10.1126/scitranslmed.3009650.

Abstract

A rapid antibiotic susceptibility test (AST) is desperately needed in clinical settings for fast and appropriate antibiotic administration. Traditional ASTs, which rely on cell culture, are not suitable for urgent cases of bacterial infection and antibiotic resistance owing to their relatively long test times. We describe a novel AST called single-cell morphological analysis (SCMA) that can determine antimicrobial susceptibility by automatically analyzing and categorizing morphological changes in single bacterial cells under various antimicrobial conditions. The SCMA was tested with four Clinical and Laboratory Standards Institute standard bacterial strains and 189 clinical samples, including extended-spectrum β-lactamase-positive Escherichia coli and Klebsiella pneumoniae, imipenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococci from hospitals. The results were compared with the gold standard broth microdilution test. The SCMA results were obtained in less than 4 hours, with 91.5% categorical agreement and 6.51% minor, 2.56% major, and 1.49% very major discrepancies. Thus, SCMA provides rapid and accurate antimicrobial susceptibility data that satisfy the recommended performance of the U.S. Food and Drug Administration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Algorithms
  • Anti-Bacterial Agents / therapeutic use*
  • Automation, Laboratory
  • Bacteria / drug effects*
  • Bacteria / isolation & purification
  • Bacteria / pathogenicity
  • Dose-Response Relationship, Drug
  • Drug Resistance, Bacterial*
  • High-Throughput Screening Assays
  • Humans
  • Image Interpretation, Computer-Assisted
  • Microbial Sensitivity Tests / methods*
  • Microbial Viability
  • Microfluidic Analytical Techniques
  • Predictive Value of Tests
  • Reproducibility of Results
  • Single-Cell Analysis / methods*
  • Time Factors
  • Time-Lapse Imaging
  • Workflow

Substances

  • Anti-Bacterial Agents