Untargeted next-generation sequencing-based first-line diagnosis of infection in immunocompromised adults: a multicentre, blinded, prospective study

被引：258

作者：

Parize, P. ^{[1
]}

Muth, E. ^{[2
]}

Richaud, C. ^{[3
]}

Gratigny, M. ^{[2
]}

Pilmis, B. ^{[1
]}

Lamamy, A. ^{[2
]}

Mainardi, J. -L. ^{[3
]}

Cheval, J. ^{[2
]}

de Visser, L. ^{[2
]}

Jagorel, F. ^{[2
]}

Ben Yahia, L. ^{[2
]}

Bamba, G. ^{[2
]}

Dubois, M. ^{[2
]}

Join-Lambert, O. ^{[4
]}

Leruez-Ville, M. ^{[4
]}

Nassif, X. ^{[4
]}

Lefort, A. ^{[5
]}

Lanternier, F. ^{[1
]}

Suarez, F. ^{[6
]}

Lortholary, O. ^{[1
]}

Lecuit, M. ^{[1
,7
]}

Eloit, M. ^{[2
,7
]}

机构：

[1] Paris Descartes Univ, Sorbonne Paris Cite, Necker Pasteur Ctr Infect Dis & Trop Med, Necker Enfants Malades Univ Hosp,Inst Imagine, Paris, France

[2] PathoQuest, Batiment Francois Jacob,28,Rue Docteur Roux, F-75015 Paris, France

[3] Univ Paris 05, European Georges Pompidou Hosp, AP HP, Dept Microbiol, Paris, France

[4] Paris Descartes Univ, Sorbonne Paris Cite, Microbiol Lab, Necker Enfants Malades Univ Hosp, Paris, France

[5] Univ Paris Diderot, Hosp Beaujon, Clichy, France

[6] Paris Descartes Sorbonne Paris Cite Univ, Necker Hosp, Dept Hematol, INSERM CNRS ERL8654 U1163,Imagine Inst, Paris, France

[7] Inst Pasteur, Biol Infect Unit, Inserm U1117, Pathogen Discovery Lab, Paris, France

来源：

CLINICAL MICROBIOLOGY AND INFECTION | 2017年 / 23卷 / 08期

关键词：

Diagnostics; Immunodeficiency; Infection; Microorganisms; Next-generation sequencing; BLOOD; BACTEREMIA; BACTERIAL; RELEVANCE; VIRUSES; SAMPLES; UPDATE;

D O I：

10.1016/j.cmi.2017.02.006

中图分类号：

R51 [传染病];

学科分类号：

100201 [内科学];

摘要：

Objective: Infections are the major cause of morbidity and mortality in immunocompromised patients. Improving microbiological diagnosis in these patients is of paramount clinical importance. Methods: We performed this multicentre, blinded, prospective, proof-of-concept study, to compare untargeted next-generation sequencing with conventional microbiological methods for first-line diagnosis of infection in 101 immunocompromised adults. Patients were followed for 30 days and their blood samples, and in some cases nasopharyngeal swabs and/or biological fluids, were analysed. At the end of the study, expert clinicians evaluated the results of both methods. The primary outcome measure was the detection rate of clinically relevant viruses and bacteria at inclusion. Results: Clinically relevant viruses and bacteria identified by untargeted next-generation sequencing and conventional methods were concordant for 72 of 101 patients in samples taken at inclusion (kappa test - 0.2, 95% CI 0.03-0.48). However, clinically relevant viruses and bacteria were detected in a significantly higher proportion of patients with untargeted next-generation sequencing than conventional methods at inclusion (36/101 (36%) vs. 11/101 (11%), respectively, p <0.001), and even when the latter were continued over 30 days (19/101 (19%), p 0.003). Untargeted next-generation sequencing had a high negative predictive value compared with conventional methods (64/65, 95% CI 0.95-1). Conclusions: Untargeted next-generation sequencing has a high negative predictive value and detects more clinically relevant viruses and bacteria than conventional microbiological methods. Untargeted next-generation sequencing is therefore a promising method for microbiological diagnosis in immunocompromised adults. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

引用

页码：574.e1 / 574.e6

页数：6

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