An Electronic Health Record-Wide Association Study to identify populations at increased risk of E. coli bloodstream infections

BackgroundEscherichia 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. MethodsWe 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. FindingsFY2022/23-2023/24 analysis included 757 (0{middle dot}3%) cases and 276,758 (99{middle dot}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{middle dot}20 times higher (95%CI 1{middle dot}08-1{middle dot}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. InterpretationApplying 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. FundingNational 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).