Emerging Technologies for Molecular Diagnosis of Sepsis

Mridu Sinha; Julietta Jupe; Hannah Mack; Todd P Coleman; Shelley M Lawrence; Stephanie I Fraley

doi:10.1128/CMR.00089-17

Emerging Technologies for Molecular Diagnosis of Sepsis

Clin Microbiol Rev. 2018 Feb 28;31(2):e00089-17. doi: 10.1128/CMR.00089-17. Print 2018 Apr.

Authors

Mridu Sinha^#¹, Julietta Jupe^#², Hannah Mack¹, Todd P Coleman^{1

3}, Shelley M Lawrence^{4

5

6

3}, Stephanie I Fraley^{7

6

3}

Affiliations

¹ Bioengineering Department, University of California, San Diego, San Diego, California, USA.
² Donald Danforth Plant Science Center, Saint Louis, Missouri, USA.
³ Center for Microbiome Innovation, University of California, San Diego, San Diego, California, USA.
⁴ Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California, San Diego, San Diego, California, USA slawrence@ucsd.edu sifraley@ucsd.edu.
⁵ Rady Children's Hospital of San Diego, San Diego, California, USA.
⁶ Clinical Translational Research Institute, University of California, San Diego, San Diego, California, USA.
⁷ Bioengineering Department, University of California, San Diego, San Diego, California, USA slawrence@ucsd.edu sifraley@ucsd.edu.

^# Contributed equally.

Abstract

Rapid and accurate profiling of infection-causing pathogens remains a significant challenge in modern health care. Despite advances in molecular diagnostic techniques, blood culture analysis remains the gold standard for diagnosing sepsis. However, this method is too slow and cumbersome to significantly influence the initial management of patients. The swift initiation of precise and targeted antibiotic therapies depends on the ability of a sepsis diagnostic test to capture clinically relevant organisms along with antimicrobial resistance within 1 to 3 h. The administration of appropriate, narrow-spectrum antibiotics demands that such a test be extremely sensitive with a high negative predictive value. In addition, it should utilize small sample volumes and detect polymicrobial infections and contaminants. All of this must be accomplished with a platform that is easily integrated into the clinical workflow. In this review, we outline the limitations of routine blood culture testing and discuss how emerging sepsis technologies are converging on the characteristics of the ideal sepsis diagnostic test. We include seven molecular technologies that have been validated on clinical blood specimens or mock samples using human blood. In addition, we discuss advances in machine learning technologies that use electronic medical record data to provide contextual evaluation support for clinical decision-making.

Keywords: DNA sequencing; biomedical engineering; diagnostic; infectious disease; microbiology techniques.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Bacteriological Techniques / standards
Bacteriological Techniques / trends*
Humans
Molecular Diagnostic Techniques / standards
Molecular Diagnostic Techniques / trends*
Sepsis / diagnosis*
Sepsis / microbiology*