Time-to-positivity in bloodstream infection is not a prognostic marker for mortality: analysis of a prospective multicentre randomized control trial

Fergus W Hamilton, Rebecca N Evans, Peter Ghazal, Alasdair P Macgowan

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Objectives
Time to positivity (TTP), calculated automatically in modern blood culture systems, is considered a proxy to microbial load and has been suggested a potential prognostic marker in bloodstream infection. In this large, multi-centre, prospectively collected cohort, our primary analysis aimed to quantify the relationship between TTP of monomicrobial blood cultures and mortality.

Methods
Data from a multi-centre randomised control trial (RAPIDO) in bloodstream infection was analysed. Bloodstream infections were classified into 13 groups/subgroups. The relationship between mortality and TTP was assessed by logistic regression, adjusted for site, organism, and clinical variables; and linear regression applied to examine the association between clinical variables and TTP. Robustness was assessed by sensitivity analysis.

Results
4,468 participants were included in RAPIDO. After exclusions, 3,462 were analysed, with the most common organisms being coagulase-negative staphylococci (1,072 patients) and E.coli (861 patients). 785 (22.7%) patients died within 28 days. We find no relationship between TTP and mortality for all groups except for Streptococci and Candida. Unexpectedly for Candida, an association with mortality with longer TTPs was identified. There was large variability between organisms and sites in TTP. Fever, age, and neutrophilia were associated with TTP.

Conclusions
Time to positivity is not associated with mortality, except in Candida spp (longer times associated with worse outcomes), and possibly in Streptococci (shorter times associated with worse outcomes). There was large variation between median times across centres, limiting external validity.
Original languageEnglish
JournalClinical Microbiology and Infection
Early online date6 Jun 2021
DOIs
Publication statusE-pub ahead of print - 6 Jun 2021

Bibliographical note

Funding Information:
The authors declare that they have no conflicts of interest. FH's time was funded by the GW4 Wellcome Doctoral Fellowship scheme. PG's time was funded by the Welsh Government and EU-ERDF funding (Ser Cymru Programme). The National Institute for Health Research (NIHR) Programme Grants for Applied Research funded the RAPIDO trial (RP-PG-0707-10043). The views and opinions expressed are those of the authors and do not necessarily reflect those of the NIHR HTA programme, the NIHR, the UK NHS or the Department of Health.

Publisher Copyright:
© 2021 European Society of Clinical Microbiology and Infectious Diseases

Keywords

  • bloodstream infection
  • time-to-positivity
  • prognostic marker
  • mortality

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