Metagenomic next-generation sequencing provides prognostic warning by identifying mixed infections in nocardiosis

Abstract

Nocardia is an opportunistic pathogen that mainly involves immunosuppressed patients and causes a high mortality rate. As an emerging approach to detect infectious pathogens, metagenomic next-generation sequencing (mNGS) was reported in the detection of Nocardia. However, there is no evidence demonstrating the effect of mNGS on the prognosis of Nocardia infection. In this retrospective study, we included 18 nocardiosis patients. Nocardia species were detected by mNGS from their clinical samples. All the patients were diagnosed with nocardiosis by clinical experts through a comprehensive evaluation. Of these 18 patients, fever is the most frequent initial symptom. Compared to traditional culture methods, mNGS provides a faster turnaround time (TAT) and higher sensitivity. Pulmonary nocardiosis was the most common clinical presentation in the study. mNGS detected 13 types of Nocardia species, of which Nocardia abscessus and Nocardia cyriacigeorgica were the most common species. The study’s most noteworthy discovery is that mNGS outperforms culture at detecting mixed infections (more than one pathogen detected in one clinical specimen, including bacteria, fungi, and excluding virus), and number of infectious species was an independent risk factor for nocardiosis patients’ prognostics after adjusting age, ICU days, gender and underlying diseases (adjusted HR = 1.47, 95% CI: 1.09-1.98, p = 0.011). As a result, we believe that by detecting mixed infections (more than one pathogenic species), mNGS can provide a clinical risk warning for the prognosis of nocardiosis.

Clinical Evaluation of Metagenomic Next-Generation Sequencing Method for the Diagnosis of Suspected Ascitic Infection in Patients with Liver Cirrhosis in a Clinical Laboratory

“…In addition, although a previous study reported that SBP is typically a monobacterial infection ( 13 ), effective antibiotic coverage of pathogens could be limited when solely based on culture, leading to severe clinical outcomes. Our results showed that mNGS could detect a large number of samples with polymicrobial infections and the 6-month mortality of those patients significantly increased, which was consistent with recent studies ( 19 – 21 ). There are several possible reasons for this.…”

Nontuberculous mycobacteria by metagenomic next-generation sequencing: Three cases reports and literature review

“…Cutadapt V2.10 (-q 25, 25 -m 50) was used to remove adapter sequences and low-quality reads. High-quality reads were mapped to the human genome (hg38, https://hgdownload.soe.ucsc.edu/downloads.html#human ) using default parameters on bwa-mem 2 V2.1, and then all unmapped reads were aligned to the NCBI nt database ( https://ftp.ncbi.nlm.nih.gov/genomes/ ) using BLAST V2.9.0 + (-task megablast -num_alignments 10 -max_hsps 1 -evalue 1e-10) ( 7 ). Alignments were required to be full-length with at least 95% sequence identity.…”

Literature Review of Pathogen Agnostic Molecular Testing of Clinical Specimens From Difficult-to-Diagnose Patients: Implications for Public Health

“…Results from mNGS supported the identification of multiple new pathogens. 3 , 17 , 38 , 47 Researchers used mNGS to detect single pathogens, 18 , 24 , 26 , 33 , 34 multiple pathogens, 29-31 , 39 , 48 , 42 and rare pathogens. 22 , 28 Results from mNGS were also used to correlate with clinical symptoms, 42 test specimens from patients with atypical or no symptoms, 21 , 40 , 49 and facilitate more accurate 28 and improved clinical care.…”

“…Metagenomic sequencing was used to determine associations between genotype and clinical phenotype, 46 elucidate etiologies, 23 , 41 , 43 , 44 , 46 investigate a pathogen's epidemiology by subsequent whole-genome capture, 50 and characterize clusters of divergent strains. 39 Additionally, in some cases, mNGS offered a faster turnaround time for results than traditional culture methods 29 and broader agnostic detection capabilities than nucleic acid amplification testing. 23 , 51 Overall, mNGS exhibits good sensitivity and specificity for diagnosing central nervous system infection and diagnostic performance during clinical application by assisting in identifying the pathogen.…”