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Diagnostic accuracy of SeptiFast multi-pathogen real-time PCR in the setting of suspected healthcare-associated bloodstream infection

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Abstract

Purpose

SeptiFast is a real-time PCR assay which targets ribosomal DNA sequences of bacteria and fungi, enabling detection and identification of the commonest pathogens in blood within a few hours, including those acquired in healthcare settings. We report here the first detailed assessment of SeptiFast that focuses on healthcare-associated bloodstream infections which develop during routine critical care.

Methods

This was a prospective multicentre study designed to compare the clinical diagnostic accuracy of SeptiFast versus microbiological culture and independent clinical adjudication. This Phase III diagnostic study was performed in an adequately sized cohort of adult patients who developed new signs of suspected bloodstream infection while receiving routine critical care.

Results

Of 1,006 new episodes of suspected bloodstream infection in 853 patients, 922 (92 %) of these episodes in 795 patients met the inclusion criteria of the study. Patients had been exposed to a median of 8 days (interquartile range 4–16) of hospital care and had received high levels of organ support and recent antibiotic exposure. The SeptiFast test, when compared with bloodstream infection at the species/genus level, had a greater specificity [0.86, 95 % confidence interval (CI) 0.83–0.88] than sensitivity (0.50, 95 % CI 0.39–0.61). There was a low prevalence of blood culture-proven pathogens (9.2 %, 95 % CI 7.4–11.2 %), and the post-test probabilities of both a positive (26.3 %, 95 % CI 19.8–33.7 %) and a negative SeptiFast test (5.6 %, 95 % CI 4.1–7.4 %) indicated potential limitations of this technology in diagnosing bloodstream infection.

Conclusion

When compared with blood culture, SeptiFast is likely to have limited utility for the diagnosis of healthcare-associated bloodstream infection in critical care patients despite its potential to deliver results more rapidly.

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Acknowledgements

We would like to thank Sister Tracey Evans for coordinating patient recruitment with Sisters Alison Royle, Alison Middleton and Elaine Coghlan. We also thank Dr. Gareth Thomas, Dr. John Hopper, Dr. Jane Eddleston, Dr. Paul Dean and all of the critical care and laboratory staff at the recruitment sites: Salford Royal NHS Foundation Trust, University Hospital of South Manchester NHS Foundation Trust, Central Manchester University Hospitals NHS Foundation Trust and East Lancashire Hospitals NHS Trust. We appreciate the molecular assay laboratory support from Pamela Davies and administration assistance from various NIHR Clinical Trial Graduate Interns during study planning and conduct: Matthew Langley, Claire Wilson, Daniel Graham and Kate Timms. We thank Dr. Neil Pendleton, Professor John Wain and Mrs Rosemary Martin for their independent leadership and contributions to the NIHR HTA Trial Steerign Committee. We would like to thank Professor Bill Ollier, Rachel Georgiou and their staff in the Research and Development Department at Salford Royal NHS Foundation Trust (the study Sponsors) for their support and advice throughout the study. The study was funded by the UK Health Technology Assessment (HTA) programme of the National Institute of Health Research: grant number NIHR HTA 08/13/16.

Conflicts of interest

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Authors and Affiliations

  1. Infection, Injury and Inflammation Research Group, Biomedical Facility, Clinical Sciences, Manchester Academic Health Sciences Centre, Salford Royal NHS Foundation Trust, Salford, Greater Manchester, M6 8HD, UK

    Geoffrey Warhurst, Satanayarana Maddi, Gordon L. Carlson & Paul Dark

  2. Intensive Care Unit, Salford Royal NHS Foundation Trust, Salford, Greater Manchester, M6 8HD, UK

    Murad Ghrew & Paul Dark

  3. Microbiology Department, Salford Royal NHS Foundation Trust, Salford, Greater Manchester, M6 8HD, UK

    Paul Chadwick

  4. Intensive Care Unit, University Hospital of South Manchester NHS Foundation Trust, Manchester, M23 9LT, UK

    Peter Alexander & Andrew Bentley

  5. Intensive Care Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, M13 9WL, UK

    John Moore & Michael Sharman

  6. Centre for Biostatistics, Faculty of Medical and Human Sciences, Institute of Population Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, M13 9PT, UK

    Graham Dunn

  7. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, OX3 9DU, UK

    Duncan Young

  8. Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester, M13 9PT, UK

    Geoffrey Warhurst, Andrew Bentley, Gordon L. Carlson & Paul Dark

Authors
  1. Geoffrey Warhurst
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  2. Satanayarana Maddi
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  3. Graham Dunn
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  4. Murad Ghrew
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  5. Paul Chadwick
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  6. Peter Alexander
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  7. Andrew Bentley
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  8. John Moore
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  9. Michael Sharman
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  10. Gordon L. Carlson
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  11. Duncan Young
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  12. Paul Dark
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Corresponding author

Correspondence to Paul Dark.

Additional information

Take home message

We report a phase III diagnostic accuracy study of SeptiFast real-time PCR in the setting of healthcare associated infection in critical care. Our main finding was that when compared with blood culture, SeptiFast is likely to have limited utility for the diagnosis of bloodstream infection despite its potential to deliver results more rapidly.

Study registration: UK Health Technology Assessment programme of the National Institute of Health Research (08/13/16).

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Warhurst, G., Maddi, S., Dunn, G. et al. Diagnostic accuracy of SeptiFast multi-pathogen real-time PCR in the setting of suspected healthcare-associated bloodstream infection. Intensive Care Med 41, 86–93 (2015). https://doi.org/10.1007/s00134-014-3551-x

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  • DOI: https://doi.org/10.1007/s00134-014-3551-x

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