Frederik Boëtius Hertz, Karen Leth Nielsen, Dmytro Strunin, Jelena Erdmann, Martin Lucas Jørgensen, Theiss Bendixen, Roshkan Srinathan, Rasmus L. Marvig, Steen Christian Rasmussen, Asger Nellemann Rasmussen, Christian S. Jensen, Jenny Dahl Knudsen, Susanne Häußler
OBJECTIVES: Integrated genomic surveillance, combining whole genome sequencing (WGS) of bacterial isolates with patient movement data, promises improved detection and prevention of pathogen transmission. However, evidence on its cost-effectiveness and clinical utility remains limited, not least because the full extent of transmission in hospital settings is difficult to capture. METHODS: We conducted a 28-month observational study at Rigshospitalet, Copenhagen, collecting patient movement data and sequencing 18 438 bacterial isolates from 7398 patients across diverse species, infection sites, and resistance profiles. We estimated the hypothetical benefits of implementing integrative WGS surveillance, assuming that continued transmission could be prevented when WGS information was acted upon immediately. RESULTS: We found that 1975 of 7398 of culture-positive hospitalized patients (26.7%) harboured a pathogen genetically related to another patient's isolate. Of those, 1359 (68.8%) had an epidemiological link in the hospital, with Enterococcus faecium by far being the most prevalent bacteria involved in transmissions. WGS-informed prevention could hypothetically generate a net savings of €1.35 million annually if transmission was stopped once a clonal isolate was detected in a second patient. Furthermore, this approach could potentially have prevented an estimated 1284 hospital-acquired infections over the 28-month study period, including 94 cases characterized by the recovery of bloodstream isolates. CONCLUSIONS: Our integrated genomic surveillance approach reveals previously unexplored transmission landscapes. We discovered that transmission is widespread, varies between species, and is not limited to resistant isolates. Our results emphasize the potential of integrated genomic surveillance, the identification of local transmission hotspots, potential for greater savings by including susceptible isolates, and an incremental cost-effectiveness ratio classification by pathogen species.