Abstract
Hospital outbreak investigations are high-stakes epidemiology. Contacts between staff and patients are numerous; environmental and community exposures are plentiful; and patients are highly vulnerable. Having the best data is paramount to understanding an outbreak in order to stop ongoing transmission and prevent future outbreaks. In the past 5 years, the high-resolution view of transmission offered by analyzing pathogen whole-genome sequencing (WGS) is increasingly part of hospital outbreak investigations. Concerns over speed and actionability, assay validation, liability, cost, and payment models lead to further opportunities for work in this area. Now accelerated by funding for COVID-19, the use of genomics in hospital outbreak investigations has firmly moved from the academic literature to more quotidian operations, with associated concerns involving regulatory affairs, data integration, and clinical interpretation. This review details past uses of WGS data in hospital-acquired infection outbreaks as well as future opportunities to increase its utility and growth in hospital infection prevention.