Association of time to positivity with disease severity in bloodstream infections—a population-based cohort study

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OBJECTIVES: Short time to positivity (TTP) has been proposed as a prognostic indicator in bloodstream infection (BSI) but results have been conflicting. The aim of this study was to explore the association between TTP and disease severity, using non-linear models. METHODS: This population-based retrospective study included all blood cultures in southern Sweden from 2021 to 2023. Using healthcare databases, BSI episodes were linked to information regarding prespecified disease severity markers at the time of culture (laboratory values and vital signs) as well as patient outcomes (intensive care admission and all-cause mortality at 30 days). The associations between TTP vs. disease severity were explored using non-linear regression models. RESULTS: The study included 12 585 unique BSI episodes, with a median (interquartile range) TTP of 12.1 (9.7-17.7) hours, and an overall 30-day mortality rate of 14.4%. Non-linear regression models indicated a higher mortality rate with shorter TTP, with a mortality rate of 20% at a TTP of 6 hours, and 30% at a TTP of 3 hours. In Enterobacterales, beta-haemolytic streptococci, Streptococcus pneumoniae, Staphylococcus aureus, as well as in polymicrobial findings, regression models indicated that shorter TTP was associated with a risk of >30% of intensive care admission or mortality, as compared with an overall rate of 18.2%. Shorter TTP was also associated with laboratory values and vital signs. For lactate, with an overall median value of 1.9 mmol/L, the model indicated a value of 3 mmol/L at a TTP of 8 hours, and at 4 mmol/L at a TTP of 4 hours. All associations with disease severity markers and outcomes were non-linear. DISCUSSION: TTP is an indicator of disease severity and prognosis in BSIs. The exponential association provides a biologically plausible explanation for previously conflicting results. Future studies should focus on determining the clinical utility of TTP.

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