Clinical perspectives in integrating whole-genome sequencing into the investigation of healthcare and public health outbreaks - hype or help?

Abstract

Outbreaks pose a significant risk to patient safety as well as being costly and time consuming to investigate. The implementation of targeted infection prevention and control measures relies on infection prevention and control teams having access to rapid results that detect resistance accurately, and typing results that give clinically useful information on the relatedness of isolates. At present, determining whether transmission has occurred can be a major challenge. Conventional typing results do not always have sufficient granularity or robustness to define strains unequivocally, and sufficient epidemiological data are not always available to establish links between patients and the environment. Whole-genome sequencing (WGS) has emerged as the ultimate genotyping tool, but has not yet fully crossed the divide between research method and routine clinical diagnostic microbiological technique. A clinical WGS service was officially established in 2014 as part of the Scottish Healthcare Associated Infection Prevention Institute to confirm or refute outbreaks in hospital settings from across Scotland. This article describes the authors' experiences with the aim of providing new insights into practical application of the use of WGS to investigate healthcare and public health outbreaks. Solutions to overcome barriers to implementation of this technology in a clinical environment are proposed.

Keywords: Healthcare-associated infections; Multi-locus sequence typing; Pulsed-field gel electrophoresis; Typing; Variable number of tandem repeats; Whole-genome sequencing.

Figure 1

Incorporation of whole-genome sequencing (WGS) into conventional outbreak analysis workflows for in-silico outbreak investigation. IPC, infection prevention and control; SPC, statistical process control; PCR, polymerase chain reaction.

Figure 2

Basis for phylogenetic analysis and increased whole-genome sequencing (WGS) discriminatory power in outbreak investigations. BORSA, borderline oxacillin-resistant Staphylococcus aureus; MRSA, meticillin-resistant S. aureus; VSEfm, vancomycin-susceptible Enterococcus faecium; VREfm, vancomycin-resistant E. faecium; CPE, carbapenemase-producing Enterobacterales; ESBL, extended-spectrum beta-lactamase.

Figure 3

Recommendations for using whole-genome sequencing (WGS) for the detection of nosocomial outbreaks. HAI, hospital-acquired infection; MRSA, meticillin-resistant Staphylococcus aureus; BORSA, borderline oxacillin-resistant S. aureus.

Figure 4

Whole-genome sequencing (WGS) clinical decision aid. HAI, hospital-acquired infection; IPC, infection prevention and control; SPC, statistical process control; MRSA, meticillin-resistant Staphylococcus aureus; PCR, polymerase chain reaction; VRE, vancomycin-resistant enterococci; SCBU, special care baby unit; MLST, multi-locus sequence typing; iGAS, invasive group A streptococcal disease.