Rapid, automated, and reliable antimicrobial susceptibility test from positive blood culture by CAST‐R
Pengfei Zhu,
Lihui Ren,
Ying Zhu,
Jing Dai,
Huijie Liu,
Yuli Mao,
Yuandong Li,
Yuehui He,
Xiaoshan Zheng,
Rongze Chen,
Xiaoting Fu,
Lili Zhang,
Lijun Sun,
Yuanqi Zhu,
Yuetong Ji,
Bo Ma,
Yingchun Xu,
Jian Xu,
Qiwen Yang
Affiliations
Pengfei Zhu
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Lihui Ren
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Ying Zhu
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College Chinese Academy of Medical Sciences Beijing China
Jing Dai
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Huijie Liu
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Yuli Mao
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Yuandong Li
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Yuehui He
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Xiaoshan Zheng
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Rongze Chen
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Xiaoting Fu
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Lili Zhang
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Lijun Sun
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Yuanqi Zhu
Department of Clinical Laboratory, Affiliated Hospital of Qingdao University Qingdao University Qingdao China
Yuetong Ji
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Bo Ma
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Yingchun Xu
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College Chinese Academy of Medical Sciences Beijing China
Jian Xu
Single‐Cell Center, CAS Key Laboratory of Biofuels, Shandong Key Laboratory of Energy Genetics and Shandong Energy Institute, Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences Qingdao China
Qiwen Yang
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College Chinese Academy of Medical Sciences Beijing China
Abstract Antimicrobial susceptibility tests (ASTs) are pivotal in combating multidrug resistant pathogens, yet they can be time‐consuming, labor‐intensive, and unstable. Using the AST of tigecycline for sepsis as the main model, here we establish an automated system of Clinical Antimicrobials Susceptibility Test Ramanometry (CAST‐R), based on D2O‐probed Raman microspectroscopy. Featuring a liquid robot for sample pretreatment and a machine learning‐based control scheme for data acquisition and quality control, the 3‐h, automated CAST‐R process accelerates AST by >10‐fold, processes 96 paralleled antibiotic‐exposure reactions, and produces high‐quality Raman spectra. The Expedited Minimal Inhibitory Concentration via Metabolic Activity is proposed as a quantitative and broadly applicable parameter for metabolism‐based AST, which shows 99% essential agreement and 93% categorical agreement with the broth microdilution method (BMD) when tested on 100 Acinetobacter baumannii isolates. Further tests on 26 clinically positive blood samples for eight antimicrobials, including tigecycline, meropenem, ceftazidime, ampicillin/sulbactam, oxacillin, clindamycin, vancomycin, and levofloxacin reveal 93% categorical agreement with BMD‐based results. The automation, speed, reliability, and general applicability of CAST‐R suggest its potential utility for guiding the clinical administration of antimicrobials.
