Evaluating the economic and health impact of proactive genomic epidemiology in a hospital setting

Background Genomic epidemiology which combines whole genome sequencing (WGS) of bacterial isolates with patient movement data, promises improved detection, prevention, and management of infection transmission, enhancing patient safety and reducing healthcare costs. However, evidence on its cost-effectiveness and clinical utility remains limited, as initial studies were restricted to selected pathogens and based on extrapolated assumptions from partial WGS data.

We conducted a 28-month observational study at Rigshospitalet, a 1 200-bed tertiary hospital in Copenhagen. The study involved collecting patient movement and WGS data for clinical isolates of 19 bacterial species, regardless of their site of isolation, or antibiotic susceptibility profile. This included sequencing of 18 940 clinical isolates from 7 760 patients. Findings We found that 27·1 % of culture-positive hospitalized patients harboured a pathogen genetically related to another patient’s isolate. 69 % had an epidemiological link, indicating transmission between patients, with Enterococcus faecium being the most prevalent. Notably, there were 2·2 times more transmissions of antibiotic-susceptible than resistant isolates. We estimated that prevention based on genomic epidemiology could potentially generate net savings of €1·25 million annually and avoid more than 750 disability adjusted life years (DALYs). Interpretation Our holistic, proactive genomic epidemiology approach reveals previously unexplored transmission landscapes. We discovered that transmission is widespread, varies significantly between species, and is not limited to resistant isolates. Our results highlight the potential for WGS-informed infection control, greater savings by including susceptible isolates, and an incremental cost-effectiveness ratio (ICER) classification by pathogen species. Funding Novo Nordisk Foundation, Beta.Health, Den Frie Forskningsfond Competing Interest Statement Martin Lucas Joergensen, Theiss Bendixen and Roshkan Srinathan were employed by Nordic Healthcare Group, Copenhagen, a private company during the study period. Funding Statement This work was funded by Department of Clinical Microbiology, Rigshospitalet, Denmark, Beta.Health (ID:1188), Den Frie Forskningsfond (DFF) (3101-00040B), and the Novo Nordisk Foundation (NNF Laureate Grant 18OC0033946). The funders had no role in designing and conducting the study, analysis, and interpretation the data, or the writing, review, and approval of the manuscript. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approval from the Ethical Committee was not necessary. Approval from the Center for Sundhed was sufficient and has been obtained according to Danish law (journaldata.center-forsundhed@ regionh.dk) The extraction of data from registries was approved by the local data protection agency (Journal-nr.: R-21015888) and registered in Pactius (P-2020-743). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data will be made available when submitted to a journal or by request.