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Reference: Gordon, NC, Price, JR, Cole, K et al., (2014). Prediction of Staphylococcus aureus antimicrobial resistance by whole-genome sequencing. Journal of clinical microbiology, 52 (4), 1182-1191.Citable link to this page:

 

Prediction of Staphylococcus aureus antimicrobial resistance by whole-genome sequencing.

Abstract: Whole-genome sequencing (WGS) could potentially provide a single platform for extracting all the information required to predict an organism's phenotype. However, its ability to provide accurate predictions has not yet been demonstrated in large independent studies of specific organisms. In this study, we aimed to develop a genotypic prediction method for antimicrobial susceptibilities. The whole genomes of 501 unrelated Staphylococcus aureus isolates were sequenced, and the assembled genomes were interrogated using BLASTn for a panel of known resistance determinants (chromosomal mutations and genes carried on plasmids). Results were compared with phenotypic susceptibility testing for 12 commonly used antimicrobial agents (penicillin, methicillin, erythromycin, clindamycin, tetracycline, ciprofloxacin, vancomycin, trimethoprim, gentamicin, fusidic acid, rifampin, and mupirocin) performed by the routine clinical laboratory. We investigated discrepancies by repeat susceptibility testing and manual inspection of the sequences and used this information to optimize the resistance determinant panel and BLASTn algorithm. We then tested performance of the optimized tool in an independent validation set of 491 unrelated isolates, with phenotypic results obtained in duplicate by automated broth dilution (BD Phoenix) and disc diffusion. In the validation set, the overall sensitivity and specificity of the genomic prediction method were 0.97 (95% confidence interval [95% CI], 0.95 to 0.98) and 0.99 (95% CI, 0.99 to 1), respectively, compared to standard susceptibility testing methods. The very major error rate was 0.5%, and the major error rate was 0.7%. WGS was as sensitive and specific as routine antimicrobial susceptibility testing methods. WGS is a promising alternative to culture methods for resistance prediction in S. aureus and ultimately other major bacterial pathogens.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's versionNotes:Copyright © 2014 Gordon et al.This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license.

Bibliographic Details

Publisher: American Society for Microbiology

Publisher Website: http://www.asm.org/

Journal: Journal of clinical microbiologysee more from them

Publication Website: http://jcm.asm.org/

Issue Date: 2014

pages:1182-1191Identifiers

Urn: uuid:fa0be368-baa2-4383-a13b-980ba8038c51

Source identifier: 447774

Eissn: 1098-660X

Doi: https://doi.org/10.1128/JCM.03117-13

Issn: 0095-1137 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Humans Staphylococcus aureus Anti-Bacterial Agents Sensitivity and Specificity Sequence Analysis, DNA Computational Biology Drug Resistance, Bacterial Genome, Bacterial Tiny URL: pubs:447774

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Author: Gordon, NC - - - Price, JR - - - Cole, K - - - Everitt, R - - - Morgan, M - - - Finney, J - institutionUniversity of Oxford Oxfor

Source: https://ora.ox.ac.uk/objects/uuid:fa0be368-baa2-4383-a13b-980ba8038c51



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