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Universal Risk Factors for Mortality in Bloodstream Infections (UNIFORM): A Systematic Review and Delphi Survey

Varon B, Palacios-Baena ZR, de Kraker MEA, Rodríguez-Baño J, Leibovici L, Paul M; UNIFORM research group.

Background: Significant variations in the variables collected in clinical studies focusing on bacteraemia lead to inconsistency in the evaluation of risk factors for mortality.

Objective: We aimed to define a minimum set of risk factors that should be assessed and reported in all studies assessing survival in bacteraemia.

Study eligibility: We conducted a systematic review including observational prospective and retrospective cohort studies that assessed all-cause mortality among patients with bacteraemia. We included only studies computing an adjusted analysis for mortality, with >500 participants.

Exposures: Independently significant risk factors for all-cause, preferably 30-day, mortality.

Data sources: PubMed was used to identify eligible studies published between 2000 and 2020. A Delphi survey among experts was used to evaluate and prioritize the factors identified by the systematic review.

Risk of bias: SIGN checklist complemented by risk of bias assessment of the adjusted analysis.

Data synthesis: Definite universal risk factors were defined as those assessed in >50% of all included studies and significant in >50% of those. Potential universal risk factors were defined as those significant in >50% of studies evaluating the factor and a subgroup analysis was performed for studies of Staphylococcus aureus bacteraemia.

Results: We included in the systematic review 62 studies, comprising more than 300,000 patients, from which a list of 17 risk factors was derived, whose association with all-cause mortality was statistically significant in most studies. The factors address baseline patient variables, the setting of infection acquisition, factors associated with the specific infection, the inflammatory response at onset of sepsis and management parameters where relevant. There were 14 risk factors for S. aureus bacteraemia.

Conclusion: We identified a minimum set of universal factors to be collected, reported, and assessed, in all future studies evaluating factors associated with mortality in bacteraemia to improve study quality and harmonization.

Keywords: Bloodstream infections; Cohort studies; Methodology; Mortality; Risk factors; Sepsis.

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