Next-Generation Sequencing to Detect Pathogens in Pediatric Febrile Neutropenia: A Single-Center Retrospective Study of 112 Cases.
blood microbiome
febrile neutropenia
metagenomics
microbial diversity
next-generation sequencing
Journal
Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
received:
01
03
2021
accepted:
27
04
2021
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
4
12
2021
Statut:
epublish
Résumé
Febrile neutropenia (FN) is a frequent complication in immunocompromised patients. However, causative microorganisms are detected in only 10% of patients. This study aimed to detect the microorganisms that cause FN using next-generation sequencing (NGS) to identify the genome derived from pathogenic microorganisms in the bloodstream. Here, we implemented a metagenomic approach to comprehensively analyze microorganisms present in clinical samples from patients with FN. FN is defined as a neutrophil count <500 cells/µL and fever ≥37.5°C. Plasma/serum samples of 112 pediatric patients with FN and 10 patients with neutropenia without fever (NE) were sequenced by NGS and analyzed by a metagenomic pipeline, PATHDET. The putative pathogens were detected by NGS in 5 of 10 FN patients with positive blood culture results, 15 of 87 FN patients (17%) with negative blood culture results, and 3 of 8 NE patients. Several bacteria that were common in the oral, skin, and gut flora were commonly detected in blood samples, suggesting translocation of the human microbiota to the bloodstream in the setting of neutropenia. The cluster analysis of the microbiota in blood samples using NGS demonstrated that the representative bacteria of each cluster were mostly consistent with the pathogens in each patient. NGS technique has great potential for detecting causative pathogens in patients with FN. Cluster analysis, which extracts characteristic microorganisms from a complex microbial population, may be effective to detect pathogens in minute quantities of microbiota, such as those from the bloodstream.
Sections du résumé
BACKGROUND
BACKGROUND
Febrile neutropenia (FN) is a frequent complication in immunocompromised patients. However, causative microorganisms are detected in only 10% of patients. This study aimed to detect the microorganisms that cause FN using next-generation sequencing (NGS) to identify the genome derived from pathogenic microorganisms in the bloodstream. Here, we implemented a metagenomic approach to comprehensively analyze microorganisms present in clinical samples from patients with FN.
METHODS
METHODS
FN is defined as a neutrophil count <500 cells/µL and fever ≥37.5°C. Plasma/serum samples of 112 pediatric patients with FN and 10 patients with neutropenia without fever (NE) were sequenced by NGS and analyzed by a metagenomic pipeline, PATHDET.
RESULTS
RESULTS
The putative pathogens were detected by NGS in 5 of 10 FN patients with positive blood culture results, 15 of 87 FN patients (17%) with negative blood culture results, and 3 of 8 NE patients. Several bacteria that were common in the oral, skin, and gut flora were commonly detected in blood samples, suggesting translocation of the human microbiota to the bloodstream in the setting of neutropenia. The cluster analysis of the microbiota in blood samples using NGS demonstrated that the representative bacteria of each cluster were mostly consistent with the pathogens in each patient.
CONCLUSIONS
CONCLUSIONS
NGS technique has great potential for detecting causative pathogens in patients with FN. Cluster analysis, which extracts characteristic microorganisms from a complex microbial population, may be effective to detect pathogens in minute quantities of microbiota, such as those from the bloodstream.
Identifiants
pubmed: 34859110
doi: 10.1093/ofid/ofab223
pii: ofab223
pmc: PMC8634086
doi:
Types de publication
Journal Article
Langues
eng
Pagination
ofab223Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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