Validation of the Sepsis MetaScore for Diagnosis of Neonatal Sepsis

Fecha de publicación: 01/06/2018 Fecha Ahead of Print: 13/04/2017

Autores de IIS La Fe

María Cernada Badía

Autor
Máximo Vento Torres

Autor

Participantes ajenos a IIS La Fe

Sweeney, TE
Wynn, JL
Serna, E
Wong, HR
Baker, HV
Khatri, P

Grupos

Perinatología

Leader

Máximo Vento Torres

Abstract

What's Known on This Subject. Neonates are at increased risk for developing sepsis, but this population often exhibits ambiguous clinical signs that complicate the diagnosis of infection. No biomarker has yet shown enough diagnostic accuracy to rule out sepsis at the time of clinical suspicion. What This Study Adds. We show that a gene-expression-based signature is an accurate objective measure of the risk of sepsis in a neonate or preterm infant, and it substantially improves diagnostic accuracy over that of commonly used laboratory-based testing. Implementation might decrease inappropriate antibiotic use. Background. Neonatal sepsis can have devastating consequences, but accurate diagnosis is difficult. As a result, up to 200 neonates with suspected sepsis are treated with empiric antibiotics for every 1 case of microbiologically confirmed sepsis. These unnecessary antibiotics enhance bacterial antibiotic resistance, increase economic costs, and alter gut microbiota composition. We recently reported an 11-gene diagnostic test for sepsis (Sepsis MetaScore) based on host whole-blood gene expression in children and adults, but this test has not been evaluated in neonates. Methods. We identified existing gene expression microarray-based cohorts of neonates with sepsis. We then tested the accuracy of the Sepsis MetaScore both alone and in combination with standard diagnostic laboratory tests in diagnosing sepsis. Results. We found 3 cohorts with a total of 213 samples from control neonates and neonates with sepsis. The Sepsis MetaScore had an area under the receiver operating characteristic curve of 0.92-0.93 in all 3 cohorts. We also found that, as a diagnostic test for sepsis, it outperformed standard laboratory measurements alone and, when used in combination with another test(s), resulted in a significant net reclassification index (0.3-0.69) in 5 of 6 comparisons. The mean point estimates for sensitivity and specificity were 95% and 60%, respectively, which, if confirmed prospectively and applied in a high-risk cohort, could reduce inappropriate antibiotic usage substantially. Conclusions. The Sepsis MetaScore had excellent diagnostic accuracy across 3 separate cohorts of neonates from 3 different countries. Further prospective targeted study will be needed before clinical application.

Datos de la publicación

ISSN/ISSNe:: 2048-7193, 2048-7207
Tipo:: Article
Páginas:: 129-135
DOI:: 10.1093/jpids/pix021
Factor de Impacto:: 1,204 SCImago ℠
Cuartil:: Q1 SCImago ℠

Documentos

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Métricas

Filiaciones

Sweeney, TE:: Stanford Univ, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA

Stanford Univ, Dept Med, Div Biomed Informat, Stanford, CA 94305 USA
Wynn, JL:: Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA

Univ Florida, Coll Med, Dept Pathol, Gainesville, FL USA

Univ Florida, Coll Med, Dept Immunol & Expt Med, Gainesville, FL USA
Cernada, M:: Instituto de Investigación. Health Research Institute, Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain

Instituto de Investigación. Univ & Polytech Hosp La Fe, Hlth Res Inst, Div Neonatol, Valencia, Spain
Serna, E:: Central Research Unit-INCLIVA, Faculty of Medicine, University of Valencia, Spain

Univ Valencia, Cent Res Unit INCLIVA, Fac Med, Valencia, Spain
Wong, HR:: Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Res Fdn, Cincinnati, OH 45221 USA
Baker, HV:: Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL USA
Vento, M:: Instituto de Investigación. Health Research Institute, Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain

Instituto de Investigación. Univ & Polytech Hosp La Fe, Hlth Res Inst, Div Neonatol, Valencia, Spain
Khatri, P:: Stanford Univ, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA

Stanford Univ, Dept Med, Div Biomed Informat, Stanford, CA 94305 USA