2505. Integration of Next-Generation Sequencing, Viral Sequencing, and Host-Response Profiling for the Diagnosis of Acute Infections
Session: Oral Abstract Session: Featured Oral Abstract
Saturday, October 7, 2017: 4:45 PM
Room: 06AB
Background: To guide treatment of infectious diseases, clinicians need sensitive, specific and rapid diagnostics. We aim to incorporate complementary methods of microbial sequencing and host-response profiling to improve the diagnosis of patients at risk for acute infections.

Methods: We enrolled 200 adult patients with systemic inflammatory response syndrome (SIRS) at the Stanford Emergency Department. Physicians with specialty training in infectious diseases conducted retrospective two-physician chart review to establish likely admission diagnoses. Blood samples were tested with a previously described 18-gene host-response integrated antibiotics decision model (IADM) that distinguishes non-infectious SIRS, bacterial infections and viral infections. Plasma samples were tested with shotgun metagenomic next-generation sequencing (NGS) and viral sequencing with VirCapSeq. A novel statistical algorithm was developed to identify contaminant organism sequences in NGS data.

Results: The physician chart review classified 99 patients (49%) as infected, 69 (35%) possibly infected and 32 (16%) non-infected. Compared to chart review, the IADM distinguished bacterial from viral infections with an area under curve of 0.85 (95% confidence interval 0.77-0.93). NGS results to date confirmed positive blood cultures in 7 of 9 patients, with 2 of 4 blood culture-positive E. coli patients turning up negative on NGS due to E. coli contamination. NGS also confirmed positive cultures from other sites in 2 of 6 patients with negative blood cultures. Preliminary VirCapSeq data from 23 patients confirmed positive viral tests in 5 of 6 patients with Hepatitis C, BK Virus, Cytomegalovirus and Epstein-Barr Virus infections. VirCapSeq did not identify a causative agent in the plasma of 11 patients with confirmed respiratory viral infection and intestinal Norovirus infection, and 6 patients with idiopathic illness. Interestingly, VirCapSeq found viral reactivation in 8 of 12 immunocompromised patients.

Conclusion: The diagnosis of suspected infections may be enhanced by integrating host-response and microbial data alongside clinical judgment. Our results and large cohort lay the foundation to demonstrate the utility of this approach and in which patients these tools may be most useful.

Henry Cheng, MS1,2, Fiona Strouts, PhD2, Timothy E. Sweeney, MD, PhD3, Thomas Briese, PhD4, Pratheepa Jeganathan, PhD5, Veda Khadka, BA2, Simone Thair, PhD6, Stephen Popper, ScD2, Sudeb Dalai, MD, MS7, Susanna Tan, MD7, Matthew Hitchcock, MD, MPH7, Ashrit Multani, MD7, Natalie Campen, BA2, Samuel Yang, MD6, Susan P. Holmes, PhD5, W. Ian Lipkin, MD4, Purvesh Khatri, PhD3 and David A. Relman, MD, FIDSA2, (1)Bioengineering, Stanford University, Stanford, CA, (2)Medicine, Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA, (3)Institute for Immunity, Transplantation, and Infections and Division of Biomedical Informatics, Department of Medicine, Stanford University, Stanford, CA, (4)Department of Epidemiology and Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, (5)Statistics, Stanford University, Stanford, CA, (6)Emergency Medicine, Stanford University Medical Center, Stanford, CA, (7)Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA

Disclosures:

H. Cheng, None

F. Strouts, None

T. E. Sweeney, Inflammatix, Inc: Employee and Shareholder , Salary

T. Briese, Roche: Columbia University has licensed VirCapSeq to Roche , Licensing agreement or royalty

P. Jeganathan, None

V. Khadka, None

S. Thair, None

S. Popper, None

S. Dalai, None

S. Tan, None

M. Hitchcock, None

A. Multani, None

N. Campen, None

S. Yang, None

S. P. Holmes, None

W. I. Lipkin, Roche: Columbia University has licensed VirCapSeq to Roche. , Licensing agreement or royalty

P. Khatri, Inflammatix, Inc.: Co-founder , Scientific Advisor and Shareholder , Licensing agreement or royalty and ownership stock

D. A. Relman, Karius: Consultant , Stock options
Arc Bio LLC: Consultant , Stock options

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