Emerging Biomarkers of Illness Severity: Urinary Metabolites Associated with Sepsis and Necrotizing Methicillin-Resistant Staphylococcus aureus Pneumonia

Lilliam Ambroggio, Todd A. Florin, Samir S. Shah, Richard Ruddy, Larisa Yeomans, Julie Trexel, Kathleen A. Stringer*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Our objective was to illustrate the potential of metabolomics to identify novel biomarkers of illness severity in a child with fatal necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). We present a case report with two control groups and a metabolomics analysis: an infant with fatal MRSA 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 1H-nuclear magnetic resonance spectrometry. Normalized metabolite concentration data from children with influenza pneumonia and healthy controls were compared by using an unpaired Student t test. To identify differentiating metabolites of MRSA pneumonia, the fold change of each metabolite was calculated by dividing each urine metabolite concentration of the patient with fatal MRSA pneumonia by the median urine concentration values of the same metabolite of the patients with influenza pneumonia and healthy controls, respectively. MetScape (http://metscape.ncibi.org/), a bioinformatics tool, was used for data visualization and interpretation. Urine metabolite concentrations previously identified as associated with sepsis in children (e.g., 3-hydroxybutyrate, carnitine, and creatinine) were higher in the patient with fatal MRSA pneumonia compared with those of patients with influenza pneumonia and healthy controls. The concentrations of additional metabolites—acetone, acetoacetate, choline, fumarate, glucose, and 3-aminoisobutyrate—were more than 25-fold higher in the patient with MRSA 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.

Original languageEnglish (US)
Pages (from-to)1033-1042
Number of pages10
JournalPharmacotherapy
Volume37
Issue number9
DOIs
StatePublished - Sep 1 2017

Fingerprint

Staphylococcal Pneumonia
Methicillin-Resistant Staphylococcus aureus
Sepsis
Pneumonia
Biomarkers
Human Influenza
Urine
Metabolomics
Control Groups
Phenotype
Fumarates
3-Hydroxybutyric Acid
Carnitine
Infection Control
Choline
Computational Biology
Creatinine
Spectrum Analysis
Magnetic Resonance Spectroscopy
Pediatrics

Keywords

  • metabolomics
  • necrotizing pneumonia
  • nuclear magnetic resonance
  • pediatrics
  • septic shock

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Ambroggio, Lilliam ; Florin, Todd A. ; Shah, Samir S. ; Ruddy, Richard ; Yeomans, Larisa ; Trexel, Julie ; Stringer, Kathleen A. / Emerging Biomarkers of Illness Severity : Urinary Metabolites Associated with Sepsis and Necrotizing Methicillin-Resistant Staphylococcus aureus Pneumonia. In: Pharmacotherapy. 2017 ; Vol. 37, No. 9. pp. 1033-1042.
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abstract = "Our objective was to illustrate the potential of metabolomics to identify novel biomarkers of illness severity in a child with fatal necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). We present a case report with two control groups and a metabolomics analysis: an infant with fatal MRSA 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 1H-nuclear magnetic resonance spectrometry. Normalized metabolite concentration data from children with influenza pneumonia and healthy controls were compared by using an unpaired Student t test. To identify differentiating metabolites of MRSA pneumonia, the fold change of each metabolite was calculated by dividing each urine metabolite concentration of the patient with fatal MRSA pneumonia by the median urine concentration values of the same metabolite of the patients with influenza pneumonia and healthy controls, respectively. MetScape (http://metscape.ncibi.org/), a bioinformatics tool, was used for data visualization and interpretation. Urine metabolite concentrations previously identified as associated with sepsis in children (e.g., 3-hydroxybutyrate, carnitine, and creatinine) were higher in the patient with fatal MRSA pneumonia compared with those of patients with influenza pneumonia and healthy controls. The concentrations of additional metabolites—acetone, acetoacetate, choline, fumarate, glucose, and 3-aminoisobutyrate—were more than 25-fold higher in the patient with MRSA 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.",
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Emerging Biomarkers of Illness Severity : Urinary Metabolites Associated with Sepsis and Necrotizing Methicillin-Resistant Staphylococcus aureus Pneumonia. / Ambroggio, Lilliam; Florin, Todd A.; Shah, Samir S.; Ruddy, Richard; Yeomans, Larisa; Trexel, Julie; Stringer, Kathleen A.

In: Pharmacotherapy, Vol. 37, No. 9, 01.09.2017, p. 1033-1042.

Research output: Contribution to journalArticle

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AU - Ambroggio, Lilliam

AU - Florin, Todd A.

AU - Shah, Samir S.

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AB - Our objective was to illustrate the potential of metabolomics to identify novel biomarkers of illness severity in a child with fatal necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). We present a case report with two control groups and a metabolomics analysis: an infant with fatal MRSA 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 1H-nuclear magnetic resonance spectrometry. Normalized metabolite concentration data from children with influenza pneumonia and healthy controls were compared by using an unpaired Student t test. To identify differentiating metabolites of MRSA pneumonia, the fold change of each metabolite was calculated by dividing each urine metabolite concentration of the patient with fatal MRSA pneumonia by the median urine concentration values of the same metabolite of the patients with influenza pneumonia and healthy controls, respectively. MetScape (http://metscape.ncibi.org/), a bioinformatics tool, was used for data visualization and interpretation. Urine metabolite concentrations previously identified as associated with sepsis in children (e.g., 3-hydroxybutyrate, carnitine, and creatinine) were higher in the patient with fatal MRSA pneumonia compared with those of patients with influenza pneumonia and healthy controls. The concentrations of additional metabolites—acetone, acetoacetate, choline, fumarate, glucose, and 3-aminoisobutyrate—were more than 25-fold higher in the patient with MRSA 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.

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