Identification of pathogens in culture-negative infective endocarditis cases by metagenomic analysis

Abstract

Pathogens identification is critical for the proper diagnosis and precise treatment of infective endocarditis. Although blood and valve cultures are the gold standard for IE pathogens detection, many cases are culture-negative, especially in patients who had received long-term antibiotic treatment, and precise diagnosis has therefore become a major challenge in the clinic. Metagenomic sequencing can provide both information on the pathogenic strain and the antibiotic susceptibility profile of patient samples without culturing, offering a powerful method to deal with culture-negative cases. In this work, we assessed the feasibility of a metagenomic approach to detect the causative pathogens in resected valves from IE patients.Using our in-house developed bioinformatics pipeline, we analyzed the sequencing results generated from both next-generation sequencing and Oxford Nanopore Technologies MinION nanopore sequencing for the direct identification of pathogens from the resected valves of seven clinically culture-negative IE patients according to the modified Duke criteria. Moreover, we were able to simultaneously characterize respective antimicrobial resistance features. This provides clinicians with valuable information to diagnose and treat IE patients after valve replacement surgery.

Infective endocarditis at a tertiary-care hospital in China

“…Previous antibiotic administration contributed to the higher incidence of negative blood culture in our study. Metagenomic analysis has recently been successfully used in detecting pathogens in culture-negative infective endocarditis [16,17], however more researches are required to prove its potential role in diagnosing culture-negative infective endocarditis.…”

High‐throughput identification and diagnostics of pathogens and pests: Overview and practical recommendations

“…In 2015, a paired‐end ultra‐HTS platform BGISEQ (www.seq500.com/en/), which is similar to the Illumina platform, was released. So far, it has been used for metagenomic detection of human pathogens (Cheng et al, ). Given its shorter read length (2 × 150 paired‐end or 400 bases single end), it is currently suboptimal for amplicon‐based detection and identification of organisms.…”

“…In 2015, a paired-end ultra-HTS platform BGISEQ (www.seq500.com/en/), which is similar to the Illumina platform, was released. So far, it has been used for metagenomic detection of human pathogens (Cheng et al, 2018). Given its shorter read reducing the error rate to a minimum (0.1%) at 9-to 11-fold consensus (Tedersoo, Tooming-Klunderud, & Anslan, 2017).…”

Blood and Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing in Pneumonia

“…Metagenomic next-generation sequencing (mNGS) has made a revolution in the mode of pathogen identification, as it can detect sequences from all pathogens including bacteria, fungi, viruses, and parasites simultaneously by untargeted sequencing DNA/RNA [1]. Since the reduction of sequencing costs, mNGS has been applied to improve the pathogenic diagnosis in various infectious diseases [2][3][4][5][6][7][8][9][10]. However, mNGS also has some weaknesses such as high human host background and microbial contaminants that may limit its sensitivity [1].…”