Innovations in Genomic AMR Surveillance

Whole genome sequencing of antimicrobial resistant (AMR) pathogens is increasingly being used for AMR surveillance, particularly in high-income countries. Innovations in genome sequencing and analysis technologies promise to revolutionise AMR surveillance and epidemiology even further. However, routine adoption of these technologies is a challenge, particularly in low- and middle-income countries. As part of a wider series of workshops and online consultations, a group of experts in AMR pathogen genomics and computational tool development conducted a situational analysis, identifying the following under-utilised innovations in genomic AMR surveillance: clinical metagenomics, environmental metagenomics, gene or plasmid tracking, and machine learning. The group recommended developing cost-effective use cases for each approach and mapping data outputs to clinical outcomes of interest to justify additional investment in capacity, training, and staff required to implement these technologies. Harmonisation and standardisation of methods, and the creation of equitable data sharing and governance frameworks, will facilitate successful implementation.NEW reports funding from Nuclear Threat Initiative, MRC, Open Philantropy and Shionogi as well as consulting fees from Nuclear Threat Initiative. VP reports funding from the Welldome Trust and NIHR. NAF reports funding from the BMGF, UKRI and NIHR. SJP is a member of the Scientific Advisory Board of Next Gen Diagnostics and was supported by Illumina to attend the ECCMID conference. EJ had partial salary cover from Wellcome Trust over the course of this work. KSB reports funding from the BBSRC and MRC and partial salary cover from Wellcome Trust and UKHSA over the course of this work. All other authors declare no conflicts of interest

Exploiting genomics for AMR Surveillance at One Health interfaces

The intersection of human, animal, and ecosystem health at ‘One Health Interfaces’ is recognised as being of key importance in the evolution and spread of antimicrobial resistance (AMR) and represents an important, and yet rarely realised opportunity to undertake vital AMR surveillance. A working group of international experts in pathogen genomics, AMR, and One Health convened to take part in a workshop series and online consultation focussed on the opportunities and challenges facing genomic AMR surveillance in a range of settings. Here we outline the working group’s discussion of the potential utility, advantages of, and barriers to, the implementation of genomic AMR surveillance at One Health interfaces and propose a series of recommendations for addressing these challenges. Embedding AMR surveillance at One Health interfaces will require the development of clear beneficial use cases, especially in low- and middle-income countries. Evidence of directionality, risks to human and animal health and potential trade implications were also identified by the working group as key issues. Addressing these challenges will be vital to enable genomic surveillance technology to reach its full potential for assessing the risk of transmission of AMR between the environment, animals, and humans at One Health Interfaces.DMM reports funding from BSAC. EJ had partial salary cover from Wellcome Trust over the course of this work. SJP is a member of the Scientific Advisory Board of Next Gen Diagnostics and was supported by Illumina to attend the ECCMID conference. NAF reports funding from the BMGF, UKRI and NIHR. KSB reports funding from the BBSRC and MRC and partial salary cover from Wellcome Trust and UKHSA over the course of this work. RNZ reports funding from the MRC UK. All other authors declare no conflicts of interest

Genomics for antimicrobial resistance surveillance to support infection prevention and control in healthcare facilities

Integration of genomic technologies into routine antimicrobial resistance (AMR) surveillance in healthcare facilities has the potential to generate rapid, actionable information for patient management and inform infection prevention and control measures in near real-time. However, substantial challenges limit the implementation of genomics for AMR surveillance in clinical settings. Through a workshop series and online consultation, international experts from across the AMR and pathogen genomics fields convened to review the evidence base underpinning the use of genomics for AMR surveillance in a range of settings. Here, we summarise the challenges and potential benefits of genomic AMR surveillance in healthcare settings identified, and outline the recommendations of the working group to realise this potential. These include the definition of viable and cost-effective use cases for genomic AMR surveillance, strengthening training competencies (particularly in bioinformatics) and building capacity at local, national and regional levels using hub and spoke models.EJ had partial salary cover from Wellcome Trust over the course of this work. KSB reports funding from the BBSRC and MRC and partial salary cover from Wellcome Trust and UKHSA over the course of this work. LYH reports funding from Pfizer Inc and honoraria from BioMerieux for lecture in 2022. BE and INO report receiving funding from the UK Department of Health and Social Care: grant managed by the Fleming Fund and work performed under the auspices of the SEQAFRICA project. INO reports funding from the Bill and Melinda Gates Foundation, JPIAMR, Wellcome Trust, Grand Challenges Africa Award, UK MCR, royalties for Genetics: Genes, Genomes and Evolution (Oxford University Press), Divining Without Seeds and for Antimicrobial Resistance in Developing Countries (Springer), consulting fees from Wellcome Trust, honoraria for Harvard University seminars and Peter Wildy Lecture Award 2023. SJP is a member of the Scientific Advisory Board of Next Gen Diagnostics and was supported by Illumina to attend the ECCMID conference. NAF reports funding from the BMGF, UKRI and NIHR. All other authors declare no conflicts of interest

Genomics for public health and international surveillance of antimicrobial resistance

Historically, epidemiological investigation and surveillance for antimicrobial resistant (AMR) bacteria has relied on relatively low-resolution isolate-based phenotypic analyses undertaken at local and national reference laboratories. Genomic sequencing has the potential to provide a far more high-resolution picture of AMR evolution and transmission and is already beginning to revolutionize how public health surveillance networks monitor and tackle AMR bacteria. However, the routine integration of genomics in surveillance pipelines still has considerable barriers to overcome. In 2022, a workshop series and online consultation brought together international experts in AMR and pathogen genomics to assess the status of genomic applications for AMR surveillance in a range of settings. Here we focus on discussions around the use of genomics for public health and international AMR surveillance, noting the potential advantages of, and barriers to, implementation and proposing recommendations from the working group to help drive the adoption of genomics in public health AMR surveillance. These include the need to build capacity for genome sequencing and analysis, harmonising, and standardising surveillance systems, developing equitable data sharing and governance frameworks and strengthening interactions and relationships among stakeholders at multiple levels.KSB reports funding from the BBSRC and MRC and partial salary cover from Wellcome Trust and UKHSA over the course of this work. EJ had partial salary cover from Wellcome Trust over the course of this work. SWL has received Receive Robert Austrian Research Award sponsored by Pfizer in 2022. DGA reports funding from the NIHR. INO reports funding from the Bill and Melinda Gates Foundation, JPIAMR, Wellcome Trust, Grand Challenges Africa Award, UK MCR, royalties for Genetics: Genes, Genomes and Evolution (Oxford University Press), Divining Without Seeds and for Antimicrobial Resistance in Developing Countries (Springer), consulting fees from Wellcome Trust, honoraria for Harvard University seminars and Peter Wildy Lecture Award 2023. DGA, BE, RSH, INO report receiving funding from the UK Department of Health and Social Care: grant managed by the Fleming Fund and work performed under the auspices of the SEQAFRICA project. LSB reports funding by Conselleria de Sanitat Universal i Salut Pública, Generalitat Valenciana, Valencia (Spain), under Plan GenT (Ref. CDEI-06/20-B). NAF reports funding from the BMGF, UKRI and NIHR. SJP is a member of the Scientific Advisory Board of Next Gen Diagnostics and was supported by Illumina to attend the ECCMID conference. All other authors declare no conflicts of interest

Evidence review and recommendations for the implementation of genomics for antimicrobial resistance surveillance: reports from an international expert group

Nearly a century after the beginning of the antibiotic era, which has been associated with unparalleled improvements in human health and reductions in mortality associated with infection, the dwindling pipeline for new antibiotic classes coupled with the inevitable spread of antimicrobial resistance (AMR) poses a major global challenge. Historically, surveillance of AMR bacteria typically relied on phenotypic analysis of isolates taken from infected individuals, which provides only a low-resolution view of the epidemiology behind an individual infection or wider outbreak. Recent years have seen increasing adoption of powerful new genomic technologies with the potential to revolutionise AMR surveillance by providing a high-resolution picture of the AMR profile of the bacteria causing infections and provide real-time actionable information for treating and preventing infection. However, many barriers remain to be overcome before genomic technologies can be adopted as a standard part of routine AMR surveillance around the world. Accordingly, the Surveillance and Epidemiology of Drug-resistant Infections Consortium (SEDRIC; www.sedric.org.uk) convened an expert working group on Genomics Surveillance for AMR to assess the benefits and challenges of using genomics for AMR surveillance. This overview, and the associated four workshop summaries detail these discussions and provide a series of recommendations from the working group that can help to realise the massive potential benefits for genomics in surveillance of AMR.KSB reports funding from the BBSRC and MRC and partial salary cover from Wellcome Trust and UKHSA over the course of this work. EJ had partial salary cover from Wellcome Trust over the course of this work. RAA reports funding unrelated to this study from Novo Nordisk, Roche, Novartis and UICC, and honoraria (unrelated to this study) from Merck&Co, Novartis, F. Hoffmann-La Roche Ltd. BE and INO report receiving funding from the UK Department of Health and Social Care: grant managed by the Fleming Fund and work performed under the auspices of the SEQAFRICA project. INO reports funding from the Bill and Melinda Gates Foundation, JPIAMR, Wellcome Trust, Grand Challenges Africa Award, UK MCR, royalties for Genetics: Genes, Genomes and Evolution (Oxford University Press), Divining Without Seeds and for Antimicrobial Resistance in Developing Countries (Springer), consulting fees from Wellcome Trust, honoraria for Harvard University seminars and Peter Wildy Lecture Award 2023. LYH reports funding from Pfizer Inc and honoraria from BioMerieux for lecture in 2022. DMM reports funding from BSAC. NEW reports funding from Nuclear Threat Initiative, MRC, Open Philantropy and Shionogi as well as consulting fees from Nuclear Threat Initiative. DMA reports funding from the NIHR. NAF reports funding from the BMGF, UKRI and NIHR. SJP is a member of the Scientific Advisory Board of Next Gen Diagnostics and was supported by Illumina to attend the ECCMID conference. All other authors declare no conflicts of interest