Enhanced performance of next-generation sequencing diagnostics compared with standard of care microbiological diagnostics in patients suffering from septic shock

Objectives: Culture-based diagnostics represent the standard of care in septic patients, but are highly insensitive and in many cases unspecific. We recently demonstrated the general feasibility of next-generation sequencing-based diagnostics using free circulating nucleic acids (cell-free DNA) in p...

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Hauptverfasser: Grumaz, Silke (VerfasserIn) , Decker, Sebastian (VerfasserIn) , Weigand, Markus A. (VerfasserIn) , Brenner, Thorsten (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: May 2019
In: Critical care medicine
Year: 2019, Jahrgang: 47, Heft: 5, Pages: e394-e402
ISSN:1530-0293
DOI:10.1097/CCM.0000000000003658
Online-Zugang:Verlag, Volltext: https://doi.org/10.1097/CCM.0000000000003658
Verlag, Volltext: https://journals.lww.com/ccmjournal/Fulltext/2019/05000/Enhanced_Performance_of_Next_Generation_Sequencing.21.aspx
Volltext
Verfasserangaben:Silke Grumaz, Christian Grumaz, Yevhen Vainshtein, Philip Stevens, Karolina Glanz, Sebastian O. Decker, Stefan Hofer, Markus A. Weigand, Thorsten Brenner, Kai Sohn

MARC

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520 |a Objectives: Culture-based diagnostics represent the standard of care in septic patients, but are highly insensitive and in many cases unspecific. We recently demonstrated the general feasibility of next-generation sequencing-based diagnostics using free circulating nucleic acids (cell-free DNA) in plasma samples of septic patients. Within the presented investigation, higher performance of next-generation sequencing-based diagnostics was validated by comparison to matched blood cultures. - Design: A secondary analysis of a prospective, observational, single-center study. - Setting: Surgical ICU of a university hospital and research laboratory. - Patients: Fifty patients with septic shock, 20 uninfected patients with elective surgery as control cohort. - Interventions: None. - Measurements and Main Results: From 256 plasma samples of 48 septic patients at up to seven consecutive time points within the 28-day observation period, cell-free DNA was isolated and analyzed by next-generation sequencing and relevance scoring. In parallel, results from culture-based diagnostics (e.g., blood culture) were obtained. Plausibility of blood culture and next-generation sequencing results as well as adequacy of antibiotic therapy was evaluated by an independent expert panel. In contrast to blood culture with a positivity rate of 33% at sepsis onset, the positivity rate for next-generation sequencing-based pathogen identification was 72%. Over the whole study period, blood culture positivity was 11%, and next-generation sequencing positivity was 71%. Ninety-six percent of positive next-generation sequencing results for acute sepsis time points were plausible and would have led to a change to a more adequate therapy in 53% of cases as assessed by the expert evaluation. - Conclusions: Our results show that next-generation sequencing-based analyses of bloodstream infections provide a valuable diagnostic platform for the identification of clinically relevant pathogens with higher sensitivity and specificity than blood culture, indicating that patients might benefit from a more appropriate therapy based on next-generation sequencing-based diagnosis. 
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