title: Bacterial nanoscale cultures for phenotypic multiplexed antibiotic susceptibility testing.
abstract: An optimal antimicrobial drug regimen is the key to successful clinical outcomes of bacterial infections. To direct the choice of antibiotic, access to fast and precise antibiotic susceptibility profiling of the infecting bacteria is critical. We have developed a high-throughput nanowell antibiotic susceptibility testing (AST) device for direct, multiplexed analysis. By processing in real time the optical recordings of nanoscale cultures of reference and clinical uropathogenic Escherichia coli strains with a mathematical algorithm, the time point when growth shifts from lag phase to early logarithmic phase (Tlag) was identified for each of the several hundreds of cultures tested. Based on Tlag, the MIC could be defined within 4 h. Heatmap presentation of data from this high-throughput analysis allowed multiple resistance patterns to be differentiated at a glance. With a possibility to enhance multiplexing capacity, this device serves as a high-throughput diagnostic tool that rapidly aids clinicians in prescribing the optimal antibiotic therapy.
authors.affiliation: Division of Proteomics and Nanobiotechnology, Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Emilie
authors.initials: E
authors.lastname: Weibull
authors.affiliation: Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Haris
authors.initials: H
authors.lastname: Antypas
authors.affiliation: Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Kjäll
authors.affiliation: Department of Clinical Microbiology, Karolinska University Hospital, and Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Annelie
authors.initials: A
authors.lastname: Brauner
authors.affiliation: Division of Proteomics and Nanobiotechnology, Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Helene
authors.initials: H
authors.lastname: Andersson-Svahn
authors.affiliation: Swedish Medical Nanoscience Center, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden Agneta.Richter.Dahlfors@ki.se.
authors.forename: Agneta
authors.initials: A
authors.lastname: Richter-Dahlfors
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D057166:High-Throughput Screening Assays / Q000295:instrumentation* / Q000379:methods*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000295:instrumentation* / Q000379:methods*; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods; D013997:Time Factors; D056689:Uropathogenic Escherichia coli / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents