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

作者: Lilliam Ambroggio , Todd A. Florin , Samir S. Shah , Richard Ruddy , Larisa Yeomans

DOI: 10.1002/PHAR.1973

关键词:

摘要: tudy Objective To illustrate the potential of metabolomics to identify novel biomarkers illness severity in a child with fatal necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Design Case report two control groups and analysis. Patients An infant MRSA pneumonia, four children influenza (pneumonia group), seven healthy no known infections (healthy group). Measurements Main Results Urine samples were collected from all children. Metabolites identified quantified using 1H-nuclear magnetic resonance spectrometry. Normalized metabolite concentration data controls compared an unpaired Student's t test. To differentiating metabolites fold change each was calculated dividing urine patient median values same patients controls, respectively. Metscape (http://metscape.ncibi.org/), bioinformatics tool, used for visualization interpretation. Urine concentrations previously as associated sepsis (e.g., 3-hydroxybutyrate, carnitine, creatinine) higher those controls. The additional metabolites—acetone, acetoacetate, choline, fumarate, glucose 3-aminoisobutyrate—were more than 25-fold controls. Conclusion These metabolic changes preceded clinical severe phenotype, which suggests that detection extent disruption can aid early identification phenotype advance diagnosis. These also support utility development assays pediatric at high risk deterioration. This article is protected copyright. All rights reserved.

参考文章(36)
Stephanie E. Reuter, Allan M. Evans, Carnitine and Acylcarnitines Clinical Pharmacokinetics. ,vol. 51, pp. 553- 572 ,(2012) , 10.1007/BF03261931
William W. Coon, George D. Zuidema, Marvin M. Kirsh, Kuang H. Wu, Barry Sherman, Verne Hoshal, The production of hyperammonemia in dogs with eck fistula Journal of Surgical Research. ,vol. 4, pp. 377- 379 ,(1964) , 10.1016/S0022-4804(64)80087-1
Joseph L. McClay, Daniel E. Adkins, Nancy G. Isern, Thomas M. O’Connell, Jan B. Wooten, Barbara K. Zedler, Madhukar S. Dasika, Bradley Todd Webb, Bobbie-Jo Webb-Robertson, Joel G. Pounds, Edward L. Murrelle, Mark F. Leppert, Edwin J. C. G. van den Oord, 1H Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function Journal of Proteome Research. ,vol. 9, pp. 3083- 3090 ,(2010) , 10.1021/PR1000048
Gurli Baer, Philipp Baumann, Michael Buettcher, Ulrich Heininger, Gerald Berthet, Juliane Schäfer, Heiner C Bucher, Daniel Trachsel, Jacques Schneider, Muriel Gambon, Diana Reppucci, Jessica M Bonhoeffer, Jody Stähelin-Massik, Philipp Schuetz, Beat Mueller, Gabor Szinnai, Urs B Schaad, Jan Bonhoeffer, None, Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infection in children and adolescents (ProPAED): a randomized controlled trial. PLOS ONE. ,vol. 8, ,(2013) , 10.1371/JOURNAL.PONE.0068419
Scott L. Weiss, Mary A. Selak, Florin Tuluc, Jose Perales Villarroel, Vinay M. Nadkarni, Clifford S. Deutschman, Lance B. Becker, Mitochondrial dysfunction in peripheral blood mononuclear cells in pediatric septic shock. Pediatric Critical Care Medicine. ,vol. 16, ,(2015) , 10.1097/PCC.0000000000000277
Karsten Suhre, Henri Wallaschofski, Johannes Raffler, Nele Friedrich, Robin Haring, Kathrin Michael, Christina Wasner, Alexander Krebs, Florian Kronenberg, David Chang, Christa Meisinger, H-Erich Wichmann, Wolfgang Hoffmann, Henry Völzke, Uwe Völker, Alexander Teumer, Reiner Biffar, Thomas Kocher, Stephan B Felix, Thomas Illig, Heyo K Kroemer, Christian Gieger, Werner Römisch-Margl, Matthias Nauck, A genome-wide association study of metabolic traits in human urine Nature Genetics. ,vol. 43, pp. 565- 569 ,(2011) , 10.1038/NG.837
Robert C. Noland, Timothy R. Koves, Sarah E. Seiler, Helen Lum, Robert M. Lust, Olga Ilkayeva, Robert D. Stevens, Fausto G. Hegardt, Deborah M. Muoio, Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control Journal of Biological Chemistry. ,vol. 284, pp. 22840- 22852 ,(2009) , 10.1074/JBC.M109.032888
Michael A. Puskarich, Michael A. Finkel, Alla Karnovsky, Alan E. Jones, Julie Trexel, Brooke N. Harris, Kathleen A. Stringer, Pharmacometabolomics of l-Carnitine Treatment Response Phenotypes in Patients with Septic Shock Annals of the American Thoracic Society. ,vol. 12, pp. 46- 56 ,(2015) , 10.1513/ANNALSATS.201409-415OC
Jonathan R. Swann, Kieran M. Tuohy, Peter Lindfors, Duncan T. Brown, Glenn R. Gibson, Ian D. Wilson, James Sidaway, Jeremy K. Nicholson, Elaine Holmes, Variation in antibiotic-induced microbial recolonization impacts on the host metabolic phenotypes of rats. Journal of Proteome Research. ,vol. 10, pp. 3590- 3603 ,(2011) , 10.1021/PR200243T
Todd A. Florin, Lilliam Ambroggio, Biomarkers for Community-Acquired Pneumonia in the Emergency Department Current Infectious Disease Reports. ,vol. 16, pp. 451- ,(2014) , 10.1007/S11908-014-0451-8