TY - JOUR
T1 - Staphylococcus aureus whole genome sequence–based susceptibility and resistance prediction using a clinically amenable workflow
AU - Cunningham, Scott A.
AU - Jeraldo, Patricio R.
AU - Schuetz, Audrey N.
AU - Heitman, Angela A.
AU - Patel, Robin
N1 - Funding Information:
We thank the Mayo Clinic Center for Individualized Medicine Microbiome Program for supporting this study. Dr. Patel is supported, in part, by UM1 AI104681 ; the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
Dr. Patel reports grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited, and Shionogi. Dr. Patel is a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, and Qvella; monies are paid to Mayo Clinic. In addition, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an antibiofilm substance issued. Dr. Patel receives travel reimbursement from ASM and IDSA; an editor's stipend from IDSA; and honoraria from the NBME, Up-to-Date, and the Infectious Diseases Board Review Course. Dr. Schuetz is a consultant for pattern Biosciences
Funding Information:
We thank the Mayo Clinic Center for Individualized Medicine Microbiome Program for supporting this study. Dr. Patel is supported, in part, by UM1 AI104681; the content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Some results presented in this manuscript were presented in abstract form at ECCMID 2019 (Amsterdam). Dr. Patel reports grants from CD Diagnostics, Merck, Hutchison Biofilm Medical Solutions, Accelerate Diagnostics, ContraFect, TenNor Therapeutics Limited, and Shionogi. Dr. Patel is a consultant to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, and Qvella; monies are paid to Mayo Clinic. In addition, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an antibiofilm substance issued. Dr. Patel receives travel reimbursement from ASM and IDSA; an editor's stipend from IDSA; and honoraria from the NBME, Up-to-Date, and the Infectious Diseases Board Review Course. Dr. Schuetz is a consultant for pattern Biosciences
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/7
Y1 - 2020/7
N2 - We used graphical user interface–based automated analytical tools from Next Gen Diagnostics (Mountain View, CA) and 1928 Diagnostics (Gothenburg, Sweden) to analyze whole genome sequence (WGS) data from 102 unique blood culture isolates of Staphylococcus aureus to predict antimicrobial susceptibly, with results compared to those of phenotypic susceptibility testing. Of 916 isolate/antibiotic combinations analyzed using the Next Gen Diagnostics tool, there were 9 discrepancies between WGS predictions and phenotypic susceptibility/resistance, including 8 for clindamycin and 1 for minocycline. Of 612 isolate/antibiotic combinations analyzed using the 1928 Diagnostics tool, there were 13 discrepancies between WGS predictions and phenotypic susceptibility/resistance, including 9 for clindamycin, 3 for trimethoprim–sulfamethoxazole, and 1 for rifampin. Trimethoprim-sulfamethoxazole was not assessed by Next Gen Diagnostics, and minocycline was not assessed by 1928 Diagnostics. There was complete concordance between phenotypic susceptibility/resistance and genotypic prediction of susceptibility/resistance using both analytical platforms for oxacillin, vancomycin, and mupirocin, as well as by the Next Gen Diagnostics analytical tool for levofloxacin (the 1928 Diagnostics tool did not assess levofloxacin). These results suggest that, from a performance standpoint, with some caveats, automatic bioinformatics tools may be acceptable to predict susceptibility and resistance to a panel of antibiotics for S. aureus.
AB - We used graphical user interface–based automated analytical tools from Next Gen Diagnostics (Mountain View, CA) and 1928 Diagnostics (Gothenburg, Sweden) to analyze whole genome sequence (WGS) data from 102 unique blood culture isolates of Staphylococcus aureus to predict antimicrobial susceptibly, with results compared to those of phenotypic susceptibility testing. Of 916 isolate/antibiotic combinations analyzed using the Next Gen Diagnostics tool, there were 9 discrepancies between WGS predictions and phenotypic susceptibility/resistance, including 8 for clindamycin and 1 for minocycline. Of 612 isolate/antibiotic combinations analyzed using the 1928 Diagnostics tool, there were 13 discrepancies between WGS predictions and phenotypic susceptibility/resistance, including 9 for clindamycin, 3 for trimethoprim–sulfamethoxazole, and 1 for rifampin. Trimethoprim-sulfamethoxazole was not assessed by Next Gen Diagnostics, and minocycline was not assessed by 1928 Diagnostics. There was complete concordance between phenotypic susceptibility/resistance and genotypic prediction of susceptibility/resistance using both analytical platforms for oxacillin, vancomycin, and mupirocin, as well as by the Next Gen Diagnostics analytical tool for levofloxacin (the 1928 Diagnostics tool did not assess levofloxacin). These results suggest that, from a performance standpoint, with some caveats, automatic bioinformatics tools may be acceptable to predict susceptibility and resistance to a panel of antibiotics for S. aureus.
KW - Antibiotics
KW - Genome
KW - Sequencing
KW - Staphylococcus aureus
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U2 - 10.1016/j.diagmicrobio.2020.115060
DO - 10.1016/j.diagmicrobio.2020.115060
M3 - Article
C2 - 32417617
AN - SCOPUS:85084540295
SN - 0732-8893
VL - 97
JO - Diagnostic Microbiology and Infectious Disease
JF - Diagnostic Microbiology and Infectious Disease
IS - 3
M1 - 115060
ER -