Skip to content
1887

Journal of Medical Microbiology logo Journal of Medical Microbiology

Volume 74, Issue 1

Investigating the time to blood culture positivity: why does it take so long? Open Access

Abstract

Bloodstream infections (BSIs) are one of the most serious infections investigated by microbiologists. However, the time to detect a BSI fails to meet the rapidity required to inform clinical decisions in real time.

Blood culture (BC) is considered the gold standard for diagnosing bloodstream infections. However, the time to blood culture positivity can be lengthy. Underpinning this is the reliance on bacteria replicating to a high concentration, which is necessary for the detection using routine blood culture systems. To improve the diagnosis and management of patients with BSIs, more sensitive detection methods are required.

The study aimed to answer key questions addressing the delay in BSI detection and whether the time to BSI detection could be expedited using a Scattered Light Integrated Collection (SLIC) device.

A proof-of-concept study was conducted to compare the time to positivity (TTP) of Gram-negative BCs flagging positive on BacT/ALERT with an SLIC device. An SLIC device was utilized to compare the TTP of the most prevalent BSI pathogens derived from nutrient broth and BC, the influence of bacterial load on TTP and the TTP directly from whole blood. Additionally, the overall turnaround time (TAT) of SLIC was compared with that of a standard hospital workflow.

Most pathogens tested took significantly longer to replicate when derived from BC than from nutrient medium. The median TTP of Gram-negative BC on BacT/ALERT was 13.56 h with a median bacterial load of 6.4×10 c.f.u. ml. All pathogens (7/7) derived from BC at a concentration of 10 c.f.u. ml were detectable in under 70 min on SLIC. Decreasing BC concentration from 10 to 10 c.f.u. ml increased the TTP of SLIC from 15 to 85 min. Direct BSI detection from whole blood on SLIC demonstrated a 76% reduction in TAT when compared with the standard hospital workflow.

An SLIC device significantly reduced the TTP of common BSI pathogens. The application of this technology could have a major impact on the detection and management of BSI.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): blood culture , bloodstream infection and rapid diagnostics
Funding
This study was supported by the:
  • University of St Andrews
    • Principle Award Recipient: KerryJane Falconer
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001942
2025-01-06
2025-01-14
Loading full text...

Full text loading...

/deliver/fulltext/jmm/74/1/jmm001942.html?itemId=/content/journal/jmm/10.1099/jmm.0.001942&mimeType=html&fmt=ahah

References

  1. Timsit J-F, Soubirou J-F, Voiriot G, Chemam S, Neuville M et al. Treatment of bloodstream infections in ICUs. BMC Infect Dis 2014; 14:489 [View Article] [PubMed]
     [Google Scholar]
  2. Viscoli C. Bloodstream infections: the peak of the iceberg. Virulence 2016; 7:248–251 [View Article] [PubMed]
     [Google Scholar]
  3. Surrey and Sussex Healthcare NHS Trust Microbiology laboratory user’s manual; 2017 https://www.surreyandsussex.nhs.uk/wp-content/uploads/2013/05/Microbiology-Laboratory-Usrs-Manual-Version-5.pdf accessed 9 January 2018
  4. Alder Hey Children’s NHS Foundation Trust A user’s guide to the medical microbiology department; 2017 https://www.alderhey.nhs.uk/wp-content/uploads/2023/09/Microbiology-2139__v1.6-User-guide-Internet.pdf accessed 9 January 2018
  5. Altun O, Almuhayawi M, Lüthje P, Taha R, Ullberg M et al. Controlled evaluation of the new BacT/Alert Virtuo blood culture system for detection and time to detection of bacteria and yeasts. J Clin Microbiol 2016; 54:1148–1151 [View Article] [PubMed]
     [Google Scholar]
  6. Public Health England UK standards for microbiology investigations: Investigation of blood cultures (for organisms other than Mycobacterium species); 2019 https://www.rcpath.org/static/a30a7f3f-503d-425b-99eb7964ef64d4fc/UK-SMI-B-37i82-September-2019-Investigation-of-blood-cultures-for-organisms-other-than-Mycobacterium-species.pdf accessed 21 June 2020
  7. Yagupsky P, Nolte FS. Quantitative aspects of septicemia. Clin Microbiol Rev 1990; 3:269–279 [View Article] [PubMed]
     [Google Scholar]
  8. Dorn GL, Land GA, Wilson GE. Improved blood culture technique based on centrifugation: clinical evaluation. J Clin Microbiol 1979; 9:391–396 [View Article] [PubMed]
     [Google Scholar]
  9. Yue P, Zhou M, Kudinha T, Xie X, Du J et al. Clinical performance evaluation of VersaTrek 528 blood culture system in a Chinese tertiary hospital. Front Microbiol 2018; 9:2027 [View Article] [PubMed]
     [Google Scholar]
  10. Jorgensen JH, Pfaller MA, Carroll KC. Manual of Clinical Microbiology, 11th ed Washington, DC: ASM Press; 2015
     [Google Scholar]
  11. Opota O, Croxatto A, Prod’hom G, Greub G. Blood culture-based diagnosis of bacteraemia: state of the art. Clin Microbiol Infect 2015; 21:313–322 [View Article] [PubMed]
     [Google Scholar]
  12. Congestrì F, Pedna MF, Fantini M, Samuelli M, Schiavone P et al. Comparison of “time to detection” values between BacT/ALERT VIRTUO and BacT/ALERT 3D instruments for clinical blood culture samples. Int J Infect Dis 2017; 62:1–5 [View Article] [PubMed]
     [Google Scholar]
  13. Anjana Gopi KL, Ravikumar MG, Ambarish NN et al. Time to positivity of microorganisms with BACTEC 9050:- an 18-month study among children of 28 days to 60 months in an south indian tertiary hospital. Int J Microbiol Res 2011; 2:12–17
     [Google Scholar]
  14. Riedel S, Eisinger SW, Dam L, Stamper PD, Carroll KC. Comparison of BD Bactec Plus Aerobic/F medium to VersaTREK Redox 1 blood culture medium for detection of Candida spp. in seeded blood culture specimens containing therapeutic levels of antifungal agents. J Clin Microbiol 2011; 49:1524–1529 [View Article] [PubMed]
     [Google Scholar]
  15. Samuel LP, Pimentel JD, Tibbetts RJ, Martin R, Hensley R et al. Comparison of time to positivity of the VersaTREK® REDOX 80-mL and the REDOX EZ draw 40-mL blood culture bottles for common bacterial bloodstream pathogens. Diagn Microbiol Infect Dis 2011; 71:101–105 [View Article] [PubMed]
     [Google Scholar]
  16. Jiang J, Yang J, Mei J, Jin Y, Lu Y. Head-to-head comparison of qSOFA and SIRS criteria in predicting the mortality of infected patients in the emergency department: a meta-analysis. Scand J Trauma Resusc Emerg Med 2018; 26:56 [View Article] [PubMed]
     [Google Scholar]
  17. Daniels R, Nutbeam T. eds The sepsis manual., 6th. edn 2022
     [Google Scholar]
  18. European Antimicrobial Resistance Surveillance Network (EARS-Net) Surveillance report: antimicrobial resistance in EU/EEA (EARS-Net); 2022 https://www.ecdc.europa.eu/sites/default/files/documents/AER-antimicrobial-resistance.pdf accessed 18 March 2024
  19. O’Neill J. Tackling drug-resistant infections globally: final report and recommendations; 2016 https://amr-review.org/sites/default/files/160518_Final%20paper_with%20cover.pdf accessed 14 March 2014
  20. Retamar P, Portillo MM, López-Prieto MD, Rodríguez-López F, de Cueto M et al. Impact of inadequate empirical therapy on the mortality of patients with bloodstream infections: a propensity score-based analysis. Antimicrob Agents Chemother 2012; 56:472–478 [View Article] [PubMed]
     [Google Scholar]
  21. Kumar A, Roberts D, Wood KE, Light B, Parrillo JE et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34:1589–1596 [View Article] [PubMed]
     [Google Scholar]
  22. Lodise TP Jr, Patel N, Kwa A, Graves J, Furuno JP et al. Predictors of 30-day mortality among patients with Pseudomonas aeruginosa bloodstream infections: impact of delayed appropriate antibiotic selection. Antimicrob Agents Chemother 2007; 51:3510–3515 [View Article] [PubMed]
     [Google Scholar]
  23. Gaieski DF, Mikkelsen ME, Band RA, Pines JM, Massone R et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med 2010; 38:1045–1053 [View Article] [PubMed]
     [Google Scholar]
  24. Paul M, Shani V, Muchtar E, Kariv G, Robenshtok E et al. Systematic review and meta-analysis of the efficacy of appropriate empiric antibiotic therapy for sepsis. Antimicrob Agents Chemother 2010; 54:4851–4863 [View Article]
     [Google Scholar]
  25. Lee C-C, Lee C-H, Hong M-Y, Tang H-J, Ko W-C. Timing of appropriate empirical antimicrobial administration and outcome of adults with community-onset bacteremia. Crit Care 2017; 21:119 [View Article]
     [Google Scholar]
  26. Robineau O, Robert J, Rabaud C, Bedos J-P, Varon E et al. Management and outcome of bloodstream infections: a prospective survey in 121 French hospitals (SPA-BACT survey). Infect Drug Resist 2018; 11:1359–1368 [View Article] [PubMed]
     [Google Scholar]
  27. Hammond RJH, Falconer K, Powell T, Bowness R, Gillespie SH. A simple label-free method reveals bacterial growth dynamics and antibiotic action in real-time. Sci Rep 2022; 12:19393 [View Article] [PubMed]
     [Google Scholar]
  28. Miles AA, Misra SS, Irwin JO. The estimation of the bactericidal power of the blood. J Hyg (Lond) 1938; 38:732–749 [View Article] [PubMed]
     [Google Scholar]
  29. UK Health Security Agency UK standards for microbiology investigations. Sepsis and systemic or disseminated infections; 2023 https://www.rcpath.org/static/3f51b8e5-1ebe-469d-a79f3a3323bfaec9/7e38a3d1-fdc7-4c6e-aadc7e55b698ef26/uk-smi-s-12i1-sepsis-and-systemic-or-disseminated-infection-january-2023-pdf.pdf accessed 21 October 2024
  30. Falconer K, Hammond R, Gillespie SH. Improving the recovery and detection of bloodstream pathogens from blood culture. J Med Microbiol 2020; 69:806–811 [View Article] [PubMed]
     [Google Scholar]
  31. Ruiz-Giardín JM, Martin-Díaz RM, Jaqueti-Aroca J, Garcia-Arata I, San Martín-López JV et al. Diagnosis of bacteraemia and growth times. Int J Infect Dis 2015; 41:6–10 [View Article] [PubMed]
     [Google Scholar]
  32. Wang M-C, Lin W-H, Yan J-J, Fang H-Y, Kuo T-H et al. Early identification of microorganisms in blood culture prior to the detection of a positive signal in the BACTEC FX system using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. J Microbiol Immunol Infect 2015; 48:419–424 [View Article] [PubMed]
     [Google Scholar]
  33. EUCAST EUCAST reading guide for broth microdilution. Version 5; 2024 https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/MIC_testing/Reading_guide_BMD_v_5.0_2024.pdf accessed 18 March 2024
  34. Minasyan H. Erythrocyte and blood antibacterial defense. Eur J Immunol 2014; 4:138–143 [View Article]
     [Google Scholar]
  35. Pishchany G, McCoy AL, Torres VJ, Krause JC, Crowe JE et al. Specificity for human hemoglobin enhances Staphylococcus aureus Infection. Cell Host & Microbe 2010; 8:544–550 [View Article]
     [Google Scholar]
  36. Pishchany G, Skaar EP. Taste for blood: hemoglobin as a nutrient source for pathogens. PLOS Pathog 2012; 8:e1002535 [View Article] [PubMed]
     [Google Scholar]
  37. Kim HK, DeDent A, Cheng AG, McAdow M, Bagnoli F et al. IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge. Vaccine 2010; 28:6382–6392 [View Article]
     [Google Scholar]
  38. Huddleson JF. Growth of bacteria in blood. use of cation exchange resins for enhancing or suppressing growth. Bulletin World Health Organisation 1959; 21:187–199
     [Google Scholar]
  39. Roome APCH, Tozer RA. Effect of dilution on the growth of bacteria from blood cultures. J Clin Pathol 1968; 21:719–721 [View Article] [PubMed]
     [Google Scholar]
  40. Lee D-H, Koh E-H, Choi S-R, Kim S, Kim DH et al. Effect of sodium citrate on growth of bacteria in blood culture. Ann Clin Microbiol 2013; 16:168 [View Article]
     [Google Scholar]
  41. Pishchany G, Haley KP, Skaar EP. Staphylococcus aureus growth using human hemoglobin as an iron source. J Vis Exp 201350072 [View Article] [PubMed]
     [Google Scholar]
  42. Diekema DJ, Hsueh P-R, Mendes RE, Pfaller MA, Rolston KV et al. The microbiology of bloodstream infection: 20-year trends from the SENTRY antimicrobial surveillance program. Antimicrob Agents Chemother 2019; 63:e00355–19 [View Article]
     [Google Scholar]
  43. Buetti N, Atkinson A, Marschall J et al. Incidence of bloodstream infections: a nationwide surveillance of acute care hospitals in Switzerland 2008-2014. BMJ Open 2017; 7:e013665 [View Article] [PubMed]
     [Google Scholar]
  44. Kumar A, Ellis P, Arabi Y, Roberts D, Light B et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009; 136:1237–1248 [View Article] [PubMed]
     [Google Scholar]
  45. Nannan Panday RS, Wang S, van de Ven PM, Hekker TAM, Alam N et al. Evaluation of blood culture epidemiology and efficiency in a large European teaching hospital. PLoS One 2019; 14:e0214052 [View Article] [PubMed]
     [Google Scholar]
  46. Falconer K, Hammond R, Parcell BJ, Gillespie SH. Rapid determination of antimicrobial susceptibility of Gram-negative bacteria from clinical blood cultures using a scattered light-integrated collection device. J Med Microbiol 2024; 73:001812 [View Article] [PubMed]
     [Google Scholar]
/content/journal/jmm/10.1099/jmm.0.001942
Loading
Investigating the time to blood culture positivity: why does it take so long?
J. Med. Microbiol. 74, 001942 (2025); https://doi.org/10.1099/jmm.0.001942
/content/journal/jmm/10.1099/jmm.0.001942
/content/journal/jmm/10.1099/jmm.0.001942
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error