title: A rapid antimicrobial susceptibility test based on single-cell morphological analysis.
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.
authors.affiliation: Center for Nanoparticle Research, Institute for Basic Science, Seoul 151-742, Republic of Korea. Department of Electrical Engineering and Computer Science, Seoul National University, Seoul 151-742, Republic of Korea. Bio-MAX Institute, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jungil
authors.initials: J
authors.lastname: Choi
authors.affiliation: QuantaMatrix Inc., Seoul 151-742, Republic of Korea.
authors.forename: Jungheon
authors.initials: J
authors.lastname: Yoo
authors.affiliation: QuantaMatrix Inc., Seoul 151-742, Republic of Korea.
authors.forename: Mincheol
authors.initials: M
authors.lastname: Lee
authors.affiliation: Center for Nanoparticle Research, Institute for Basic Science, Seoul 151-742, Republic of Korea. Department of Electrical Engineering and Computer Science, Seoul National University, Seoul 151-742, Republic of Korea. Bio-MAX Institute, Seoul National University, Seoul 151-742, Republic of Korea. QuantaMatrix Inc., Seoul 151-742, Republic of Korea.
authors.forename: Eun-Geun
authors.initials: EG
authors.lastname: Kim
authors.affiliation: Interdisciplinary Program of Bioengineering, Seoul National University Graduate School, Seoul 151-742, Republic of Korea.
authors.forename: Ji Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Incheon St. Mary's Hospital, The Catholic University School of Medicine, Incheon 403-720, Republic of Korea.
authors.forename: Seungok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
authors.forename: Seik
authors.initials: S
authors.lastname: Joo
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
authors.forename: Eui-Chong
authors.initials: EC
authors.lastname: Kim
authors.affiliation: Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-799, Republic of Korea. Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Department of Biomedical Engineering, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
authors.forename: Jung Chan
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul 110-799, Republic of Korea. Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. Department of Biomedical Engineering, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
authors.forename: Hee Chan
authors.initials: HC
authors.lastname: Kim
authors.affiliation: QuantaMatrix Inc., Seoul 151-742, Republic of Korea. skwon@snu.ac.kr jygpaul@quantamatrix.com.
authors.forename: Yong-Gyun
authors.initials: YG
authors.lastname: Jung
authors.affiliation: Center for Nanoparticle Research, Institute for Basic Science, Seoul 151-742, Republic of Korea. Department of Electrical Engineering and Computer Science, Seoul National University, Seoul 151-742, Republic of Korea. Bio-MAX Institute, Seoul National University, Seoul 151-742, Republic of Korea. QuantaMatrix Inc., Seoul 151-742, Republic of Korea. skwon@snu.ac.kr jygpaul@quantamatrix.com.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kwon
mesh_terms: D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D057205:Automation, Laboratory; D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D057166:High-Throughput Screening Assays; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008826:Microbial Sensitivity Tests / Q000379:methods*; D050296:Microbial Viability; D046210:Microfluidic Analytical Techniques; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D059010:Single-Cell Analysis / Q000379:methods*; D013997:Time Factors; D059008:Time-Lapse Imaging; D057188:Workflow
chemical_list: D000900:Anti-Bacterial Agents