Abstract
Background Bloodstream infections (BSI), are common, life threatening infections. However, it remains unclear whether deaths following BSI are primarily due to uncontrolled infection or underlying comorbidities. We aimed to determine the overall mortality, infection-attributable mortality, and causes of death for four leading BSI pathogens.
Methods This retrospective cohort study was conducted within the SAIL Databank, containing anonymised population-scale electronic health record data for Wales, UK. We included adults with Escherichia coli, Klebsiella sp, Pseudomonas aeruginosa and Staphylococcus aureus BSI between 2010-2022 using linked data from Public Health Wales and the Office for National Statistics. 30-day all-cause and sepsis-specific mortality, as a proxy for infection-attributable mortality, were compared using Cox proportional hazards and competing risk regression respectively.
Findings We identified 35,691 adults with BSI. E. coli was the most prevalent (59.6%). Adjusted analyses revealed that all organisms had a higher 30-day mortality vs. E. coli with MRSA the highest (HR: 2.04 [1.83-2.37], p<0.001).
Cancer was the leading cause of death following BSI for all organisms, particularly deaths occurring between 30-90 days (35.9%). 25.5% of deaths within 30 days involved sepsis. MRSA was associated with the highest sepsis mortality vs. E. coli (HR: 2.45 [2.12-2.82], p<0.001). Peak CRP was positively associated with increased sepsis mortality (p<0.001).
Interpretation This population-level study challenges the assumption that most deaths following BSI are directly attributable to uncontrolled infection. Our findings underscore the need for re-evaluating clinical trial design and developing better preventative strategies for BSI.
Funding This work is funded by the Medical Research Council [grant number MR/T023791/1].
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
This work and Jonathan Underwood are funded by the Medical Research Council [grant number MR/T023791/1]. The authors and their institutions did not at any time receive any other specific payment or services from a third party for any aspect of the submitted work.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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This project uses anonymised individual-level data sources held within the Trusted Research Environment provided by the SAIL Databank at Swansea University, Swansea, UK. All proposals to use SAIL data are subject to review by the independent Information Governance Review Panel (IGRP). This work was approved under proposal number 0923 after careful considerations by IGRP Panel.
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Data Availability
This project uses anonymised individual-level data sources held within the Trusted Research Environment provided by the SAIL Databank at Swansea University, Swansea, UK. All proposals to use SAIL data are subject to review by the independent Information Governance Review Panel (IGRP). As such, data is not available for sharing without explicit permission by the IGRP.