RT Journal Article
SR Electronic
T1 Fast I(n)dentification of Pathogens in Neonates (FINDPATH-N): protocol for a prospective pilot cohort study of next-generation sequencing for pathogen identification in neonates with suspected sepsis
JF BMJ Paediatrics Open
JO BMJ Paediatrics Open
FD BMJ Publishing Group Ltd
SP e000651
DO 10.1136/bmjpo-2020-000651
VO 4
IS 1
A1 Jennifer Ann Klowak
A1 Salhab el Helou
A1 Jeffrey M Pernica
A1 Melissa J Parker
A1 Michael Surette
A1 Hendrik Poinar
A1 Alison E Fox-Robichaud
A1 ,
YR 2020
UL http://bmjpaedsopen.bmj.com/content/4/1/e000651.abstract
AB Introduction Sepsis is a major source of morbidity and mortality in neonates; however, identification of the causative pathogens is challenging. Many neonates have negative blood cultures despite clinical evidence of sepsis. Next-generation sequencing (NGS) is a high-throughput, parallel sequencing technique for DNA. Pathogen-targeted enrichment followed by NGS has the potential to be more sensitive and faster than current gold-standard blood culture. In this pilot study, we will test the feasibility and pathogen detection patterns of pathogen-targeted NGS in neonates with suspected sepsis. Additionally, the distribution and diagnostic accuracy of biomarkers cell-free DNA and protein C levels at two time points will be explored.Methods and analysis We will conduct a prospective, pilot observational study. Neonates over 1 kg with suspected sepsis from a single tertiary care children’s hospital will be recruited for the study. Recruitment will be censored at 200 events or 6 months’ duration. Two blood study samples will be taken: the first simultaneous to the blood culture (time=0 hour, for NGS and biomarkers) via an exception to consent (deferred consent) and another 24 hours later after prospective consent (biomarkers only). Neonates will be adjudicated into those with clinical sepsis, culture-proven sepsis and without sepsis based on clinical criteria. Feasibility parameters (eg, recruitment) and NGS process time will be reported.For analysis, NGS results will be described in aggregate, compared with the simultaneous blood culture (sensitivity and specificity) and reviewed via expert panel for plausibility. Pilot data for biomarker distribution and diagnostic accuracy (sensitivity and specificity) for distinguishing between septic and non-septic neonates will be reported.Ethics and dissemination Ethics approval has been granted by the Hamilton Integrated Research Ethics Board. We will seek publication of study results in peer-reviewed journals.