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

• Verfasst von: Grumaz, Silke [VerfasserIn]
• Verfasst von: Decker, Sebastian [VerfasserIn]
• Verfasst von: Weigand, Markus A. [VerfasserIn]
• Verfasst von: Brenner, Thorsten [VerfasserIn]
• Titel: Enhanced performance of next-generation sequencing diagnostics compared with standard of care microbiological diagnostics in patients suffering from septic shock
• Verf.angabe: Silke Grumaz, Christian Grumaz, Yevhen Vainshtein, Philip Stevens, Karolina Glanz, Sebastian O. Decker, Stefan Hofer, Markus A. Weigand, Thorsten Brenner, Kai Sohn
• E-Jahr: 2019
• Jahr: May 2019
• Umfang: 9 S.
• Fussnoten: Gesehen am 12.08.2019
• Titel Quelle: Enthalten in: Critical care medicine
• Ort Quelle: Hagerstown, Md. : Lippincott Williams & Wilkins, 1973
• Jahr Quelle: 2019
• Band/Heft Quelle: 47(2019), 5, Seite e394-e402
• ISSN Quelle: 1530-0293
• DOI: doi:10.1097/CCM.0000000000003658
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1671184890

Abstract

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.