{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T20:06:46Z","timestamp":1778011606998,"version":"3.51.4"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018625","name":"Science and Technology Innovation Plan Of Shanghai Science and Technology Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Bloodstream infection is a life-threatening complication in critically ill patients. Multi-drug resistant bacteria or fungi may increase the risk of invasive infections in hospitalized children and are difficult to treat in intensive care units. The purpose of this study was to use metagenomic next-generation sequencing (mNGS) to understand the bloodstream microbiomes of children with suspected sepsis in a pediatric intensive care unit (PICU). mNGS were performed on microbial cell-free nucleic acid from 34 children admitted to PICU, and potentially pathogenic microbes were identified. The associations of serological inflammation indicators, lymphocyte subpopulations, and other clinical phenotypes were also examined. mNGS of blood samples from children in PICU revealed potential eukaryotic microbial pathogens. The abundance of <jats:italic>Pneumocystis jirovecii<\/jats:italic> was positively correlated with a decrease in total white blood cell count and immunodeficiency. Hospital-acquired pneumonia patients showed a significant increase in blood bacterial species richness compared with community-acquired pneumonia children. The abundance of bloodstream bacteria was positively correlated with serum procalcitonin level. Microbial genome sequences from potential pathogens were detected in the bloodstream of children with suspected sepsis in PICU, suggesting the presence of bloodstream infections in these children.<\/jats:p>","DOI":"10.3389\/fcimb.2021.665226","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T11:07:42Z","timestamp":1629803262000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":45,"title":["Metagenomic Next-Generation Sequencing of Bloodstream Microbial Cell-Free Nucleic Acid in Children With Suspected Sepsis in Pediatric Intensive Care Unit"],"prefix":"10.3389","volume":"11","author":[{"given":"Gangfeng","family":"Yan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhao","family":"Tao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodi","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingbang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoping","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00386-19","article-title":"Viruses in Vietnamese Patients Presenting With Community-Acquired Sepsis of Unknown Cause","volume":"57","author":"Anh","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s00134-020-05943-5","article-title":"Critical Care Management of Adults With Community-Acquired Severe Respiratory Viral Infection","volume":"46","author":"Arabi","year":"2020","journal-title":"Intensive Care Med."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e27734","DOI":"10.1002\/pbc.27734","article-title":"Cell-Free DNA Next-Generation Sequencing Successfully Detects Infectious Pathogens in Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients at Risk for Invasive Fungal Disease","volume":"66","author":"Armstrong","year":"2019","journal-title":"Pediatr. Blood Cancer"},{"key":"B4","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1080\/21505594.2015.1134072","article-title":"Bloodstream Infections in the Intensive Care Unit","volume":"7","author":"Bassetti","year":"2016","journal-title":"Virulence"},{"key":"B5","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/s41564-018-0349-6","article-title":"Analytical and Clinical Validation of a Microbial Cell-Free DNA Sequencing Test for Infectious Disease","volume":"4","author":"Blauwkamp","year":"2019","journal-title":"Nat. Microbiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ebiom.2018.07.017","article-title":"BKV, CMV, and EBV Interactions and Their Effect on Graft Function One Year Post-Renal Transplantation: Results From a Large Multi-Centre Study","volume":"34","author":"Blazquez-Navarro","year":"2018","journal-title":"EBioMedicine"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A Flexible Trimmer for Illumina Sequence Data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"18738","DOI":"10.1073\/pnas.1906320116","article-title":"A Cell-Free DNA Metagenomic Sequencing Assay That Integrates the Host Injury Response to Infection","volume":"116","author":"Cheng","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B9","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1056\/NEJM200008173430707","article-title":"Epstein-Barr Virus Infection","volume":"343","author":"Cohen","year":"2000","journal-title":"N. Engl. J. Med."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2018.00405","article-title":"Transcriptomic Abnormalities in Epstein Barr Virus Associated T\/NK Lymphoproliferative Disorders","volume":"6","author":"de Mel","year":"2018","journal-title":"Front. Pediatr."},{"key":"B11","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/s41564-019-0637-9","article-title":"Metagenomic Sequencing With Spiked Primer Enrichment for Viral Diagnostics and Genomic Surveillance","volume":"5","author":"Deng","year":"2020","journal-title":"Nat. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"13336","DOI":"10.1073\/pnas.1517494112","article-title":"Noninvasive Monitoring of Infection and Rejection After Lung Transplantation","volume":"112","author":"De Vlaminck","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1164\/rccm.201705-0983LE","article-title":"Clinical Metagenomics for the Diagnosis of Hospital-Acquired Infections: Promises and Hurdles","volume":"196","author":"Emonet","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1111\/j.1439-0507.2009.01715.x","article-title":"Molecular Diagnosis of Pneumocystis Jiroveci Pneumonia in Immunocompromised Patients","volume":"53","author":"Jarboui","year":"2010","journal-title":"Mycoses"},{"key":"B15","doi-asserted-by":"publisher","first-page":"334","DOI":"10.3855\/jidc.11056","article-title":"Enterobacterial Infection in Saudi Arabia: First Record of Klebsiella Pneumoniae With Triple Carbapenemase Genes Resistance","volume":"13","author":"Khan","year":"2019","journal-title":"J. Infect. Dev. Ctries"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2590","DOI":"10.1111\/crj.12961","article-title":"The Association Between Cytomegalovirus Co-Infection With Pneumocystis Pneumonia and Mortality in Immunocompromised Non-HIV Patients","volume":"12","author":"Korkmaz Ekren","year":"2018","journal-title":"Clin. Respir. J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"9623","DOI":"10.1073\/pnas.1707009114","article-title":"Numerous Uncharacterized and Highly Divergent Microbes Which Colonize Humans are Revealed by Circulating Cell-Free DNA","volume":"114","author":"Kowarsky","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B18","doi-asserted-by":"publisher","first-page":"ofaa109","DOI":"10.1093\/ofid\/ofaa109","article-title":"High Carriage Rates of Multidrug-Resistant Gram-Negative Bacteria in Neonatal Intensive Care Units From Ghana","volume":"7","author":"Labi","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00697","article-title":"How to Optimize the Use of Blood Cultures for the Diagnosis of Bloodstream Infections? A State-of-the Art","volume":"7","author":"Lamy","year":"2016","journal-title":"Front. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3546","DOI":"10.1128\/JCM.01555-07","article-title":"Detection of Bloodstream Infections in Adults: How Many Blood Cultures Are Needed","volume":"45","author":"Lee","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2216","DOI":"10.1093\/cid\/ciz901","article-title":"Pneumocystis Infection Outbreaks in Organ Transplantation Units in France: A Nation-Wide Survey","volume":"70","author":"Le Gal","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and Accurate Short Read Alignment With Burrows-Wheeler Transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00005","article-title":"Identification and Characterization of Blood and Neutrophil-Associated Microbiomes in Patients With Severe Acute Pancreatitis Using Next-Generation Sequencing","volume":"8","author":"Li","year":"2018","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13756-020-00728-3","article-title":"Five-Year Change of Prevalence and Risk Factors for Infection and Mortality of Carbapenem-Resistant Klebsiella Pneumoniae Bloodstream Infection in a Tertiary Hospital in North China","volume":"9","author":"Li","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3201\/eid1901.120140","article-title":"Pneumocystis Jirovecii Genotype Associated With Increased Death Rate of HIV-Infected Patients With Pneumonia","volume":"19","author":"Rabodonirina","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e0218318","DOI":"10.1371\/journal.pone.0218318","article-title":"Metagenomic Next-Generation Sequencing of Samples From Pediatric Febrile Illness in Tororo, Uganda","volume":"14","author":"Ramesh","year":"2019","journal-title":"PloS One"},{"key":"B27","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1080\/14737159.2018.1498786","article-title":"16S Metagenomics for Diagnosis of Bloodstream Infections: Opportunities and Pitfalls","volume":"18","author":"Rutanga","year":"2018","journal-title":"Expert Rev. Mol. Diagn."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00188","article-title":"Cytomegalovirus: A Troll in the ICU? Overview of the Literature and Perspectives for the Future","volume":"7","author":"Schildermans","year":"2020","journal-title":"Front. Med. (Lausanne)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/bioinformatics\/btr026","article-title":"Quality Control and Preprocessing of Metagenomic Datasets","volume":"27","author":"Schmieder","year":"2011","journal-title":"Bioinformatics"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1016\/S0140-6736(17)31002-4","article-title":"Neonatal Sepsis","volume":"390","author":"Shane","year":"2017","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1007\/s00134-020-05950-6","article-title":"Bloodstream Infections in Critically Ill Patients: An Expert Statement","volume":"46","author":"Timsit","year":"2020","journal-title":"Intensive Care Med."},{"key":"B32","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0140-6736(09)61569-5","article-title":"Accurate and Rapid Identification of Bacterial Species From Positive Blood Cultures With a DNA-Based Microarray Platform: An Observational Study","volume":"375","author":"Tissari","year":"2010","journal-title":"Lancet"},{"key":"B33","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.bbi.2018.10.006","article-title":"Alteration of Gut Microbiota-Associated Epitopes in Children With Autism Spectrum Disorders","volume":"75","author":"Wang","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00321-18","article-title":"Alterations in Gut Glutamate Metabolism Associated With Changes in Gut Microbiota Composition in Children With Autism Spectrum Disorder","volume":"4","author":"Wang","year":"2019","journal-title":"mSystems"},{"key":"B35","doi-asserted-by":"publisher","first-page":"e0202049","DOI":"10.1371\/journal.pone.0202049","article-title":"Detection of Pathogenic Bacteria in the Blood From Sepsis Patients Using 16S rRNA Gene Amplicon Sequencing Analysis","volume":"13","author":"Watanabe","year":"2018","journal-title":"PloS One"},{"key":"B36","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1080\/14787210.2017.1305887","article-title":"Diagnosis and Management of Pneumocystis Jirovecii Infection","volume":"15","author":"White","year":"2017","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1056\/NEJMoa1401268","article-title":"Actionable Diagnosis of Neuroleptospirosis by Next-Generation Sequencing","volume":"370","author":"Wilson","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1002\/ana.24499","article-title":"Diagnosing Balamuthia Mandrillaris Encephalitis With Metagenomic Deep Sequencing","volume":"78","author":"Wilson","year":"2015","journal-title":"Ann. Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.bbi.2019.06.039","article-title":"Altered Gut Microbiota and Mucosal Immunity in Patients With Schizophrenia","volume":"85","author":"Xu","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"B40","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12941-017-0191-3","article-title":"Systematic Review and Meta-Analysis of Mortality of Patients Infected With Carbapenem-Resistant Klebsiella Pneumoniae","volume":"16","author":"Xu","year":"2017","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"B41","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.jnutbio.2018.09.016","article-title":"Association of Serum Bilirubin in Newborns Affected by Jaundice With Gut Microbiota Dysbiosis","volume":"63","author":"Zhou","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1093\/cid\/ciy802","article-title":"Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children","volume":"68","author":"Zinter","year":"2019","journal-title":"Clin. Infect. Dis."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.665226\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T11:07:46Z","timestamp":1629803266000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2021.665226\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,24]]},"references-count":42,"alternative-id":["10.3389\/fcimb.2021.665226"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2021.665226","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,24]]},"article-number":"665226"}}