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Review
. 2025 Apr;25(4):e235-e244.
doi: 10.1016/S1473-3099(24)00729-1. Epub 2025 Jan 17.

A framework towards implementation of sequencing for antimicrobial-resistant and other health-care-associated pathogens

Alison Laufer Halpin  1 , Amy J Mathers  2 , Timothy R Walsh  3 , Walter Zingg  4 , Iruka N Okeke  5 , L Clifford McDonald  6 , Christopher A Elkins  6 , Stephan Harbarth  7 , Sharon J Peacock  8 , Arjun Srinivasan  6 , Michael Bell  6 , Didier Pittet  7 , Denise Cardo  6 ; 3rd Geneva Infection Prevention and Control Think Tank
Collaborators, Affiliations
Review

A framework towards implementation of sequencing for antimicrobial-resistant and other health-care-associated pathogens

Alison Laufer Halpin et al. Lancet Infect Dis. 2025 Apr.

Abstract

Antimicrobial resistance continues to be a growing threat globally, specifically in health-care settings in which antimicrobial-resistant pathogens cause a substantial proportion of health-care-associated infections (HAIs). Next-generation sequencing (NGS) and the analysis of the data produced therein (ie, bioinformatics) represent an opportunity to enhance our capacity to address these threats. The 3rd Geneva Infection Prevention and Control Think Tank brought together experts to identify gaps, propose solutions, and set priorities for the use of NGS for HAIs and antimicrobial-resistant pathogens. The major deliverable recommendation from this meeting was a proposed framework for implementing the sequencing of HAI pathogens, specifically those harbouring antimicrobial-resistance mechanisms. The key components of the proposed framework relate to wet laboratory quality, sequence data quality, database and tool selection, bioinformatic analyses, data sharing, and NGS data integration, to support public health and actions for infection prevention and control. In this Personal View we detail and discuss the framework in the context of global implementation, specifically in low-income and middle-income countries.

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Conflict of interest statement

Declaration of interests ESS reports support from the US Centers for Disease Control and Prevention (CDC; Cooperative Agreement CK-22-2203) for this manuscript; funding from the CDC, Administration for Strategic Preparedness and Response, Massachusetts Institute for Technology; royalties from Up to Date (mpox chapter); consulting fees from BARDA/CARB-X/Boston University; and committee involvement for CDC Healthcare, the Infection Control and Prevention Advisory Committee, Boston Biosafety Commission, Massachusetts Infectious Diseases Society, SHEA Public Policy and Government Affairs Committee (Chair) and High Level Disinfection and Sterilization Guidelines Committee (Co-chair), all outside of the submitted work. VC-CC reports support from the Health and Medical Research Fund (CID-HKU1-16) to his institution; participation on the Society for Healthcare Epidemiologists of America Publication Committee and a committee for Clean Hospitals International Expert Network; and serving as Editor or Editorial Board membership for the Journal of Hospital Infection, Infection Prevention in Practice, Infection Control & Hospital Epidemiology, Antimicrobial Stewardship & Healthcare Epidemiology, and Frontiers in Public Health. NAF reports support from UK National Institute for Health and Care Research (NIHR; global health professorship). NPG reports support from NIHR, CDC, UK Medical Research Council, and the Bill & Melinda Gates Foundation to their institution; participation on a Data Safety Monitoring or Advisory Board for the ACACIA trial, DREAMM project, and 5FC Crypto project; and participation on the Federation of Infectious Diseases Societies of Southern Africa. SH reports consultant fees from Destiny Pharma outside of the submitted work. MKH reports support from CDC and service as President of SHEA Board of Trustees. INO reports support from the Gates Foundation, Wellcome Trust, Fleming Fund/Mott McDonald, Grand Challenges Africa (award GCA/DD/rnd3/021), NIHR (project NIHR133307), International Vaccine Institute Award, outside of the submitted work; and participation on the Thomas Bassir Biomedical Foundation Nigeria Board and the International Centre for Antimicrobial Resistance Solutions Technical Advisory Forum. SJP reports service on the Scientific Advisory Board for Next Gen Diagnostics. SP reports support from the German Center for Infectious Research outside of the submitted work. MHS reports support from the US Department of Veterans Affairs, CDC, and Agency for Healthcare Research and Quality, outside of the submitted work. All other authors and members of the 3rd Geneva Infection Prevention and Control Think Tank declare no competing interests.

Figures

Figure 1.
Figure 1.
Sliding scale of NGS Applications. *Indicates public health interface and utility is applicable for more than one purpose. Acronyms: Antimicrobial resistance (AR); Core genome multilocus sequence typing (cgMLST); High quality single nucleotide variant (hqSNV); Identification (ID); Infection prevention and control (IPC)
Figure 2.
Figure 2.
Collaboration and infrastructure are critical for implementing next generation sequencing (NGS). This figure provides a detailed example of how NGS for infection prevention and control (IPC) could be implemented to inform actions and a complementary table of considerations for NGS/IPC applications. Acronyms: Infection prevention and control (IPC)
Figure 3.
Figure 3.
Standard versus Prospective Sequencing approaches for healthcare outbreak response. Demonstration of how sequencing prospectively may change the framework and timing of outbreak detection and response. Sequencing run times vary based on the instrument selected, throughput, read length, and coverage: Illumina MiSeq instruments run ~17-56 hours, Illumina NextSeq instruments run ~11-30 hours, and Oxford Nanopore Technology instruments run ~6-24 hours. Infection prevention investigations (i.e., evaluating epidemiologic, clinical, and laboratory data) timing will vary based on the facility’s resources.
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