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We present a case report with two control groups and a metabolomics analysis: an infant with fatal <jats:styled-content style=\"fixed-case\">MRSA<\/jats:styled-content> pneumonia, four children with influenza pneumonia (pneumonia control group), and seven healthy children with no known infections (healthy control group). Urine samples were collected from all children. Metabolites were identified and quantified using <jats:sup>1<\/jats:sup>H\u2010nuclear magnetic resonance spectrometry. Normalized metabolite concentration data from children with influenza pneumonia and healthy controls were compared by using an unpaired Student <jats:italic>t<\/jats:italic> test. To identify differentiating metabolites of <jats:styled-content style=\"fixed-case\">MRSA<\/jats:styled-content> pneumonia, the fold change of each metabolite was calculated by dividing each urine metabolite concentration of the patient with fatal <jats:styled-content style=\"fixed-case\">MRSA<\/jats:styled-content> pneumonia by the median urine concentration values of the same metabolite of the patients with influenza pneumonia and healthy controls, respectively. MetScape (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/metscape.ncibi.org\/\">http:\/\/metscape.ncibi.org\/<\/jats:ext-link>), a bioinformatics tool, was used for data visualization and interpretation. Urine metabolite concentrations previously identified as associated with sepsis in children (e.g., 3\u2010hydroxybutyrate, carnitine, and creatinine) were higher in the patient with fatal <jats:styled-content style=\"fixed-case\">MRSA<\/jats:styled-content> pneumonia compared with those of patients with influenza pneumonia and healthy controls. The concentrations of additional metabolites\u2014acetone, acetoacetate, choline, fumarate, glucose, and 3\u2010aminoisobutyrate\u2014were more than 25\u2010fold higher in the patient with <jats:styled-content style=\"fixed-case\">MRSA<\/jats:styled-content> pneumonia than those of patients with influenza pneumonia and healthy controls. These metabolic changes in the urine preceded the clinical severe sepsis phenotype, suggesting that detection of the extent of metabolic disruption can aid in the early identification of a sepsis phenotype in advance of the clinical diagnosis. These data also support the utility of metabolomics for the development of clinical assays to identify patients with pediatric pneumonia at high risk for deterioration.<\/jats:p>","DOI":"10.1002\/phar.1973","type":"journal-article","created":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T13:52:42Z","timestamp":1497966762000},"page":"1033-1042","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Emerging Biomarkers of Illness Severity: Urinary Metabolites Associated with Sepsis and Necrotizing Methicillin\u2010Resistant <i>Staphylococcus aureus<\/i> Pneumonia"],"prefix":"10.1002","volume":"37","author":[{"given":"Lilliam","family":"Ambroggio","sequence":"first","affiliation":[{"name":"Division of Hospital Medicine Cincinnati Children's Hospital Medical Center Cincinnati Ohio"},{"name":"Division of Biostatistics and Epidemiology Cincinnati Children's Hospital Medical Center Cincinnati Ohio"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd A.","family":"Florin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Ohio"},{"name":"Division of Emergency Medicine Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samir S.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Hospital Medicine Cincinnati Children's Hospital Medical Center Cincinnati Ohio"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Ohio"},{"name":"Division of Infectious Diseases Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Ruddy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Ohio"},{"name":"Division of Emergency Medicine Cincinnati Children's Hospital Medical Center Cincinnati Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larisa","family":"Yeomans","sequence":"additional","affiliation":[{"name":"Nuclear Magnetic Resonance Metabolomics Laboratory University of Michigan Ann Arbor Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Trexel","sequence":"additional","affiliation":[{"name":"Nuclear Magnetic Resonance Metabolomics Laboratory University of Michigan Ann Arbor Michigan"},{"name":"Department of Clinical Pharmacy College of Pharmacy University of Michigan Ann Arbor Michigan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0238-7774","authenticated-orcid":false,"given":"Kathleen A.","family":"Stringer","sequence":"additional","affiliation":[{"name":"Nuclear Magnetic Resonance Metabolomics 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