Next-generation sequencing diagnostics of bacteremia in sepsis (Next GeneSiS-Trial): Study protocol of a prospective, observational, noninterventional, multicenter, clinical trial. Issue 6 (February 2018)

• Record Type: Journal Article
• Authors: Brenner, Thorsten; Decker, Sebastian O.; Grumaz, Silke; Stevens, Philip; Bruckner, Thomas; Schmoch, Thomas; Pletz, Mathias W.; Bracht, Hendrik; Hofer, Stefan; Marx, Gernot; Weigand, Markus A.; Sohn, Kai
• Is Part Of: Medicine. Volume 97:Issue 6(2018)
• Publication Date: 2018-02
• Subjects: bacteremia -- blood culture -- next generation sequencing -- procalcitonin -- sepsis -- sequential organ failure assessment (SOFA) score; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000009868
• Languages: English
• ISSNs: 0025-7974

Abstract

Abstract: Background: Sepsis remains a major challenge, even in modern intensive care medicine. The identification of the causative pathogen is crucial for an early optimization of the antimicrobial treatment regime. In this context, culture-based diagnostic procedures (e.g., blood cultures) represent the standard of care, although they are associated with relevant limitations. Accordingly, culture-independent molecular diagnostic procedures might be of help for the identification of the causative pathogen in infected patients. The concept of an unbiased sequence analysis of circulating cell-free DNA (cfDNA) from plasma samples of septic patients by next-generation sequencing (NGS) has recently been identified to be a promising diagnostic platform for critically ill patients suffering from bloodstream infections. Although this new approach might be more sensitive and specific than culture-based state-of-the-art technologies, additional clinical trials are needed to exactly define the performance as well as clinical value of a NGS-based approach. Methods: Next GeneSiS is a prospective, observational, noninterventional, multicenter study to assess the diagnostic performance of a NGS-based approach for the detection of relevant infecting organisms in patients with suspected or proven sepsis [according to recent sepsis definitions (sepsis-3)] by the use of the quantitative sepsis indicating quantifier (SIQ) score in comparison to standard (culture-based) microbiological diagnostics. The clinical value of this NGS-based approach will be estimated by a panel of independent clinical specialists, retrospectively identifying potential changes in patients' management based on NGS results. Further subgroup analyses will focus on the clinical value especially for patients suffering from a failure of empiric treatment within the first 3 days after onset [as assessed by death of the patient or lack of improvement of the patient's clinical condition (in terms of an inadequate decrease of SOFA-score) or persistent high procalcitonin levels]. Discussion: This prospective, observational, noninterventional, multicenter study for the first time investigates the performance as well as the clinical value of a NGS-based approach for the detection of bacteremia in patients with sepsis and may therefore be a pivotal step toward the clinical use of NGS in this indication. Trial registration: DRKS-ID: DRKS00011911 (registered October 9, 2017)https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011911 ; ClinicalTrials.gov Identifier: NCT03356249 (registered November 29, 2017)https://clinicaltrials.gov/ct2/show/NCT03356249 Abstract : Supplemental Digital Content is available in the text