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Mortality Risk Profiling of Staphylococcus aureus Bacteremia by Multi-omic Serum Analysis Reveals Early Predictive and Pathogenic Signatures.
Wozniak, Jacob M; Mills, Robert H; Olson, Joshua; Caldera, J R; Sepich-Poore, Gregory D; Carrillo-Terrazas, Marvic; Tsai, Chih-Ming; Vargas, Fernando; Knight, Rob; Dorrestein, Pieter C; Liu, George Y; Nizet, Victor; Sakoulas, George; Rose, Warren; Gonzalez, David J.
Afiliação
  • Wozniak JM; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La
  • Mills RH; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La
  • Olson J; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jo
  • Caldera JR; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Sepich-Poore GD; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
  • Carrillo-Terrazas M; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La
  • Tsai CM; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
  • Vargas F; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Knight R; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA; D
  • Dorrestein PC; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA.
  • Liu GY; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
  • Nizet V; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jo
  • Sakoulas G; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La Jolla, CA 92093, USA; Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.
  • Rose W; School of Pharmacy, School of Medicine and Public Health University of Wisconsin-Madison, Madison, WI 53705, USA; Department of Medicine, School of Medicine and Public Health University of Wisconsin-Madison, Madison, WI 53705, USA.
  • Gonzalez DJ; Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA; Collaborative to Halt Antibiotic-Resistant Microbes, University of California, San Diego, La
Cell ; 182(5): 1311-1327.e14, 2020 09 03.
Article em En | MEDLINE | ID: mdl-32888495
ABSTRACT
Staphylococcus aureus bacteremia (SaB) causes significant disease in humans, carrying mortality rates of ∼25%. The ability to rapidly predict SaB patient responses and guide personalized treatment regimens could reduce mortality. Here, we present a resource of SaB prognostic biomarkers. Integrating proteomic and metabolomic techniques enabled the identification of >10,000 features from >200 serum samples collected upon clinical presentation. We interrogated the complexity of serum using multiple computational strategies, which provided a comprehensive view of the early host response to infection. Our biomarkers exceed the predictive capabilities of those previously reported, particularly when used in combination. Last, we validated the biological contribution of mortality-associated pathways using a murine model of SaB. Our findings represent a starting point for the development of a prognostic test for identifying high-risk patients at a time early enough to trigger intensive monitoring and interventions.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 4_TD Problema de saúde: 4_sepsis Assunto principal: Infecções Estafilocócicas / Staphylococcus aureus / Bacteriemia Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Laos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Contexto em Saúde: 4_TD Problema de saúde: 4_sepsis Assunto principal: Infecções Estafilocócicas / Staphylococcus aureus / Bacteriemia Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Laos