The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria: Report from the EUCAST subcommittee
Open accessAbstract
Whole genome sequencing (WGS) offers the potential to predict antimicrobial susceptibility from a single assay. The European Committee on Antimicrobial Susceptibility Testing established a subcommittee to review the current development status of WGS for bacterial antimicrobial susceptibility testing (AST). The published evidence for using WGS as a tool to infer antimicrobial susceptibility accurately is currently either poor or non-existent and the evidence / knowledge base requires significant expansion. The primary comparators for assessing genotypic-phenotypic concordance from WGS data should be changed to epidemiological cut-off values in order to improve differentiation of wild-type from non-wild-type isolates (harbouring an acquired resistance). Clinical breakpoints should be a secondary comparator. This assessment will reveal whether genetic predictions could also be used to guide clinical decision making. Internationally agreed principles and quality control (QC) metrics will facilitate early harmonization of analytical approaches and interpretive criteria for WGS-based predictive AST. Only data sets that pass agreed QC metrics should be used in AST predictions. Minimum performance standards should exist and comparative accuracies across different WGS laboratories and processes should be measured. To facilitate comparisons, a single public database of all known resistance loci should be established, regularly updated and strictly curated using minimum standards for the inclusion of resistance loci. For most bacterial species the major limitations to widespread adoption for WGS-based AST in clinical laboratories remain the current high-cost and limited speed of inferring antimicrobial susceptibility from WGS data as well as the dependency on previous culture because analysis directly on specimens remains challenging. For most bacterial species there is currently insufficient evidence to support the use of WGS-inferred AST to guide clinical decision making. WGS-AST should be a funding priority if it is to become a rival to phenotypic AST. This report will be updated as the available evidence increases.
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Determination of antibiotic resistance by whole genome sequencing has limitations such as a need to cultivate the isolates in order to isolate their genomic DNA.
“Deter mination of antibiotic resistance by the whole genome sequencing, however, has limitations such as a need to cultivate the isolates, in order to isolate their genomic DNA (Ellington et al., 2017).”
From Exploring the resistome of probiotics, starter cultures, and cheeses via metagenomic analysis (2025) · cites this paper as Ellington et al., 2017
The Epidemiological information section (page unavailable) describes metagenomic sequencing of DNA extracted directly from clinical samples, although it requires more reads than sequencing a pure culture. The Background section (page unavailable) likewise says WGS directly from a clinical sample is technically possible for tuberculosis, but less reliable and prohibitively expensive for clinical practice at the time. Cultivation is therefore not a necessary step to obtain genomic DNA for WGS, as the claim states. (LLM, conf=0.86)
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Buono, S. A., Wu, A., Hess, D. C., et al. (2012) · Microbial Drug Resistance · doi:10.1089/mdr.2011.0229 · Cited by 18 · see citing works
Arena, F., Rolfe, A., Doran, G., Conte, V., Gruszka, S., Clarke, T., Adesokan, Y., Giani, T., & Rossolini, G. M. (2014) · Journal of Clinical Microbiology · doi:10.1128/jcm.03247-13 · Cited by 15 · see citing works
Discovery of β-lactam-resistant variants in diverse pneumococcal populations
Hakenbeck, R. (2014) · Genome Medicine · doi:10.1186/s13073-014-0072-8 · Cited by 15 · see citing works
Ginn, A. N., Wiklendt, A. M., Zong, Z., et al. (2014) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2014.02.010 · Cited by 13 · see citing works
Computational inference of grammars for larger-than-gene structures from annotated gene sequences
Tsafnat, G., Schaeffer, J., Clayphan, A. J., et al. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr036 · Cited by 7 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [136]136. 136Clinical and Laboratory Standards Institute. Susceptibility testing of Myco- bacteria, Nocardiae, and other aerobic actinomycetes, 2nd edition approved standard. CLSI document m24-a2. Washington, DC: CLSI; 2011.
- [143]143. EUCAST. Workshop on recommendations for pharmaceutical companies regarding data required for new antituberculous drugs. Basel: Switzerland; 11e12 November 2014. Available at: http://www.Eucast.Org/fileadmin/src/ media/pdfs/eucast_files/mycobacteria/mycobacterial_workshop_basel_11- 12nov2014.Pdf (accessed 19.10.2015).
Cited by
Sorted by citations
Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection
Gu, W., Miller, S., & Chiu, C. Y. (2019) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012751 · Cited by 1,458 · see citing works
Simner, P. J., Miller, S., & Carroll, K. C. (2018) · Clinical Infectious Diseases · doi:10.1093/cid/cix881 · Cited by 821 · see citing works
Genus-Wide Assessment of Antibiotic Resistance in <i>Lactobacillus</i> spp
Campedelli, I., Mathur, H., Salvetti, E., Clarke, S., Rea, M. C., Torriani, S., Ross, R. P., Hill, C., & O’Toole, P. W. (2019) · Applied and Environmental Microbiology · doi:10.1128/aem.01738-18 · Cited by 343 · see citing works
Diagnostic Stewardship: Opportunity for a Laboratory–Infectious Diseases Partnership
Patel, R., & Fang, F. C. (2018) · Clinical Infectious Diseases · doi:10.1093/cid/ciy077 · Cited by 127 · see citing works
Exploring the resistome of probiotics, starter cultures, and cheeses via metagenomic analysis
Rozman, V., Stopnišek, N., Lorbeg, P. M., Obermajer, T., Kušar, D., & Matijašić, B. B. (2025) · Food Control · doi:10.1016/j.foodcont.2025.111173 · Cited by 12 · see citing works
“Determination of antibiotic resistance by the whole genome sequencing, however, has limitations such as a need to cultivate the isolates, in order to isolate their genomic DNA (Ellington et al., 2017).”
Influential
- Authors
- Ellington, M. J., Ekelund, O., Aarestrup, F. M., Canton, R., Doumith, M., Giske, C., Grundman, H., Hasman, H., Holden, M. T. G., Hopkins, K. L., Iredell, J., Kahlmeter, G., Köser, C. U., MacGowan, A., Mevius, D., Mulvey, M., Naas, T., Peto, T., Rolain, J.-M., Samuelsen, Ø., & Woodford, N.
- Affiliations
- Public Health England (GB)
- Region Kronoberg (SE)
- Technical University of Denmark (DK)
- Karolinska University Hospital (SE)
- University of Freiburg (DE)
- Statens Serum Institut (DK)
- University of St Andrews (GB)
- The University of Sydney (AU)
- University of Cambridge (GB)
- North Bristol NHS Trust (GB)
- Utrecht University (NL)
- Assistance Publique – Hôpitaux de Paris (FR)
- John Radcliffe Hospital (GB)
- Centre National de la Recherche Scientifique (FR)
- University Hospital of North Norway (NO)
- Corresponding author
- Woodford, N.
- ORCID
- Venue
- Clinical Microbiology and Infection
- Publisher
- Elsevier BV
- Published
- 2017-01
- Volume
- 23
- Issue
- 1
- Pages
- 2-22
- ISSN
- 1198-743X (ISSN-L)
- OpenAlex
- W2551267404
- Semantic Scholar
- 5fde3a1ac293128d5228d2cf052770458d87db66
- Cited by
- 603
- References
- 193
- Citations by year
- 2026: 73 · 2025: 70 · 2024: 56 · 2023: 61 · 2022: 52 · 2021: 87 · 2020: 53 · 2019: 58 · 2018: 55 · 2017: 36 · 2015: 1
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Clinical Microbiology and Infection (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Socio-Environmental Systems Modeling (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
- St Andrews Research Repository (St Andrews Research Repository) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Swedish Heart and Lung Foundation
- Marianne and Marcus Wallenberg Foundation
- Accelerate Diagnostics
- Achaogen Inc
- Allecra Therapeutics
- Amplex
- AstraZeneca UK Ltd
- Basilea Pharmaceutica
- Becton Dickinson Diagnostics
- BioMérieux
- Bio-Rad Laboratories
- The BSAC, Cepheid
- Check-Points B.V.
- Cubist Pharmaceuticals
- Department of Health
- Enigma Diagnostics
- Food Standards Agency
- GlaxoSmithKline Services Ltd
- Henry Stewart Talks
- IHMA Ltd
- Kalidex Pharmaceuticals
- Melinta Therapeutics
- Merck Sharpe & Dohme Corp
- Meiji Seika Pharma Co
- Mobidiag
- Momentum Biosciences Ltd
- Nordic Pharma Ltd
- Norgine Pharmaceuticals
- Rempex Pharmaceuticals Ltd
- Roche, Rokitan Ltd
- Smith & Nephew UK Ltd
- Trius Therapeutics
- VenatoRx Pharmaceuticals
- Wockhardt Ltd
- National Health and Medical Research Council of Australia (1001021)
- AstraZeneca
- Cepheid
- Ferrer International Laboratories
- MSD
- Ministry of Economic Affairs
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Bacterial Identification and Susceptibility Testing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Keywords
- whole genome sequencing, antimicrobial susceptibility testing, antimicrobial resistance prediction, epidemiological cut-off values, clinical breakpoints, quality control metrics, clinical decision-making, phenotypic drug susceptibility testing, EUCAST
- MeSH terms
- Anti-Bacterial Agents, Bacteria, Europe, Microbial Sensitivity Tests, Genome, Bacterial, Internationality
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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