Clinical implementation of routine whole-genome sequencing for hospital infection control of multi-drug resistant pathogens

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. Materials/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 (MSLT) 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 four years (April 2017 to July 2021) 2,660 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 three 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 one 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.

Genus-wide genomic characterization of Macrococcus: insights into evolution, population structure, and functional potential

“…4.3. Future genomic sequencing, metadata collection, and phenotypic characterization efforts are needed to gain insight into Macrococcus population structure, antimicrobial resistance, and virulence potential WGS has proven to be revolutionary in the food, veterinary, and human clinical microbiology spaces and is being used for-among other applications-pathogen surveillance, outbreak and cluster detection, source tracking, and diagnostics (Rossen et al, 2018;Brown et al, 2021;Ferdinand et al, 2021;Forde et al, 2023). Massive WGS efforts are being undertaken to query bacterial pathogens such as Salmonella enterica, Escherichia coli, and Listeria monocytogenes (Allard et al, 2016;Stevens et al, 2017;Brown et al, 2019), and large amounts of genomic data and metadata are publicly available for these organisms.…”

HAIviz: an interactive dashboard for visualising and integrating healthcare-associated genomic epidemiological data

“…Pathogen genomics has emerged as a valuable tool for outbreak control and pathogen surveillance in healthcare settings [1][2][3][4]. The analysis of genome sequences enables detailed characterisation of pathogen relatedness, facilitating more accurate identification of outbreak clusters [5][6][7].…”