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. 2023 Feb 8;76(3):e1277-e1284.
doi: 10.1093/cid/ciac726.

Clinical Implementation of Routine Whole-genome Sequencing for Hospital Infection Control of Multi-drug Resistant Pathogens

Brian M Forde  1 , Haakon Bergh  2 , Thom Cuddihy  1 , Krispin Hajkowicz  3 , Trish Hurst  3 , E Geoffrey Playford  4 , Belinda C Henderson  4 , Naomi Runnegar  4   5 , Julia Clark  6   7 , Amy V Jennison  8 , Susan Moss  8 , Anna Hume  2   3 , Hugo Leroux  9 , Scott A Beatson  10 , David L Paterson  1   3 , Patrick N A Harris  1   2
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Clinical Implementation of Routine Whole-genome Sequencing for Hospital Infection Control of Multi-drug Resistant Pathogens

Brian M Forde et al. Clin Infect Dis. .

Abstract

Background: Prospective whole-genome sequencing (WGS)-based surveillance may be the optimal approach to rapidly identify transmission of multi-drug resistant (MDR) bacteria in the healthcare setting.

Methods: We prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL-E), and carbapenemase-producing Enterobacterales (CPE) isolated from blood cultures, sterile sites, or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. WGS was used to determine in silico multi-locus sequence typing (MLST) and resistance gene profiling via a bespoke genomic analysis pipeline. Putative transmission events were identified by comparison of core genome single nucleotide polymorphisms (SNPs). Relevant clinical meta-data were combined with genomic analyses via customised automation, collated into hospital-specific reports regularly distributed to infection control teams.

Results: Over 4 years (April 2017 to July 2021) 2660 isolates were sequenced. This included MDR gram-negative bacilli (n = 293 CPE, n = 1309 ESBL), MRSA (n = 620), and VRE (n = 433). A total of 379 clinical reports were issued. Core genome SNP data identified that 33% of isolates formed 76 distinct clusters. Of the 76 clusters, 43 were contained to the 3 target hospitals, suggesting ongoing transmission within the clinical environment. The remaining 33 clusters represented possible inter-hospital transmission events or strains circulating in the community. In 1 hospital, proven negligible transmission of non-multi-resistant MRSA enabled changes to infection control policy.

Conclusions: Implementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions.

Keywords: clinical implementation; healthcare-associated infections; infection prevention and control; multi-resistant organisms; whole genome sequencing.

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Conflict of interest statement

Potential conflicts of interest. P. N. A. H. reports research grants from Merck, Sandoz, and Shionogi, outside the submitted work; has served on advisory boards for Sandoz and Merck, and has received speaker's fees from Pfizer, Sandoz, and Sumitomo. D. L. P reports research grants from Merck, Pfizer, and Shionogi outside the submitted work; has received honoraria for advisory board membership from Merck, Pfizer, Shionogi, GSK, QPex, Entasis, VenatoRx, BioMerieux, and Accelerate. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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