Every year approximately 200,000 Australians experience a healthcare-associated infection (HAI). The impact is exacerbated by increasing rates of antibiotic resistance. There is limited capacity in clinical laboratories to routinely track pathogens causing HAI in real-time or to detect cross-transmission events. Here, we established a pre-emptive whole-genome sequencing (WGS)-based surveillance program to identify clustering of clinically relevant multi-drug resistant (MDR) bacteria, suggesting in-hospital transmission, before outbreaks could be established or recognised.
We prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing Enterobacterales (CPE) isolated from sterile sites or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. Whole genome sequencing (Illumina NextSeq) 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 variants (SNVs). Combined with automated transfer of clinical meta-data from the laboratory information system, the genomic analyses were collated into hospital- and pathogen-specific reports and distributed to infection control teams at least monthly.
Over four years (November 2017 to November 2021) more than 2800 MDR isolates were sequenced. This included MDR gram-negatives (n=276 CPE, n=1152 ESBL and n=105 other non-ESBL/CPE), MRSA (n=610) and VRE (n=425). Core genome SNV data identified that >30% of isolates formed 76 distinct clusters that were not identifiable using traditional surveillance techniques. One cluster was related to a previous outbreak of CRAB, thought to have been resolved, prompting a targeted engineering response preventing further transmission. The remaining 33 clusters represented inter-hospital transmission events or strains circulating in the community acquired prior to hospital admission. In one hospital, the lack of hospital transmission of non-multi-resistant MRSA enabled changes to infection control policy.
Implementation of routine WGS for MDR pathogens in clinical laboratories is feasible and reveals previously unknown transmission events, which can enable targeted infection control responses.