학술논문

Clinical application of cell-free next-generation sequencing for infectious diseases at a tertiary children’s hospital
Document Type
article
Source
BMC Infectious Diseases. 21(1)
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Pediatric
Clinical Research
Infectious Diseases
Detection
screening and diagnosis
4.1 Discovery and preclinical testing of markers and technologies
4.2 Evaluation of markers and technologies
Infection
Good Health and Well Being
Adolescent
Cell-Free Nucleic Acids
Child
Child
Preschool
Communicable Diseases
Diagnostic Tests
Routine
Female
High-Throughput Nucleotide Sequencing
Hospitals
Pediatric
Humans
Male
Metagenome
Metagenomics
Retrospective Studies
Cell-free plasma
Next-generation sequencing
Children
Microbiology
Medical Microbiology
Clinical sciences
Medical microbiology
Public health
Language
Abstract
BackgroundChildren affected by infectious diseases may not always have a detectable infectious etiology. Diagnostic uncertainty can lead to prolonged hospitalizations, inappropriately broad or extended courses of antibiotics, invasive diagnostic procedures, and difficulty predicting the clinical course and outcome. Cell-free plasma next-generation sequencing (cfNGS) can identify viral, bacterial, and fungal infections by detecting pathogen DNA in peripheral blood. This testing modality offers the ability to test for many organisms at once in a shotgun metagenomic approach with a rapid turnaround time. We sought to compare the results of cfNGS to conventional diagnostic test results and describe the impact of cfNGS on clinical care in a diverse pediatric population at a large academic children's hospital.MethodsWe performed a retrospective chart review of hospitalized subjects at a tertiary pediatric hospital to determine the diagnostic yield of cfNGS and its impact on clinical care.ResultsWe describe the clinical application of results from 142 cfNGS tests in the management of 110 subjects over an 8-month study period. In comparison to conventional testing as a reference standard, cfNGS was found to have a positive percent agreement of 89.6% and negative percent agreement of 52.3%. Furthermore, 32.4% of cfNGS results were directly applied to make a clinical change in management.ConclusionsWe demonstrate the clinically utility of cfNGS in the management of acutely ill children. Future studies, both retrospective and prospective, are needed to clarify the optimal indications for testing.