An Electronic Health Record-Wide Association Study to identify populations at increased risk ofE. colibloodstream infections

Background Escherichia coli bloodstream infections (BSIs) have been under mandatory surveillance in the UK for fifteen years, but cases continue to rise. Systematic searches of all features present within electronic healthcare records (EHRs), described here as an EHR-wide association study (EHR-WAS), could potentially identify under-appreciated factors that could be targeted to reduce infections.

We used data from Oxfordshire, UK, and an EHR-WAS method developed for use with large-scale COVID-19 data to estimate associations between E. coli BSI cases, hospital-exposed controls, and 377 potential risk factors using Poisson regression models adjusted for potential confounders for three two-year financial year (FY) periods. Findings FY2022/23-2023/24 analysis included 757 (0·3%) cases and 276,758 (99·7%) controls. We identified six broad disease areas associated with increased and decreased risk of E. coli BSIs. Selected renal/urological/urinary tract infection-related variables had the largest impact on risk, with 47% risk theoretically removed if prevalence of these factors could be minimised. Cancer-related variables were also associated with higher E. coli BSI risk (e.g. 1·20 times higher (95%CI 1·08-1·34) for every three months closer chemotherapy was delivered in the last year) as were gastrointestinal disease-related and infectious disease-related variables. Selected cardiac/respiratory-related variables were associated with lower E. coli BSI risk, whereas healthcare exposure had mixed effects. Associated factors varied across periods; however, broad groups were similar. Interpretation Applying an EHR-WAS approach, we show E. coli BSIs are largely driven by known risk factors and frailty, potentially explaining why enhanced surveillance has not reduced incidence. Funding National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with UK Health Security Agency (NIHR200915). Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was funded by the National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University in partnership with the UK Health Security Agency (UKHSA) (NIHR200915) and the NIHR Biomedical Research Centre, Oxford. DWE is supported by a Robertson Fellowship. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research, the Department of Health or the UKHSA. 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: The data used in this study, the Infections in Oxfordshire Research Database (IORD), has approvals from the National Research Ethics Service South Central-Oxford C Research Ethics Committee (19/SC/0403), Health Research Authority and Confidentiality Advisory Group (19/CAG/0144) as a deidentified database without individual consent. 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 The datasets analysed during the current study are not publicly available as they contain personal data but are available from the Infections in Oxfordshire Research Database (https://oxfordbrc.nihr.ac.uk/research-themes-overview/antimicrobial-resistance-and-modernising-microbiology/infections-in-oxfordshire-research-database-iord/), subject to an application and research proposal meeting the ethical and governance requirements of the Database. For further details on how to apply for access to the data and for a research proposal template please email iord{at}ndm.ox.ac.uk.