Application of mNGS in the Etiological Analysis of Lower Respiratory Tract Infections and the Prediction of Drug Resistance

Liu, Haibing; Zhang, Yue; Yang, Jun; Liu, Yanfang; Chen, Jianguo

doi:10.1128/spectrum.02502-21

Cited by 29 publications

(27 citation statements)

References 26 publications

(28 reference statements)

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“…With the application of mNGS, more pathogen types have been detected, especially opportunistic pathogens ( 33 ). In this case, interpreting mNGS results accurately and identifying opportunistic pathogens in the corresponding patients remain difficult to achieve ( 34 ). In the present study, a number of opportunistic pathogenic microorganisms were identified by blood mNGS, but these positive results posed interpretational challenges; partial results should be interpreted within the context of its limitations.…”

Section: Discussionmentioning

confidence: 99%

Application value of blood metagenomic next-generation sequencing in patients with connective tissue diseases

Yan

et al. 2022

Front. Immunol.

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ObjectiveThis study aimed to analyze the application value of blood metagenomic next-generation sequencing (mNGS) in patients with connective tissue diseases (CTDs) to provide a reference for infection diagnosis and guidance for treatment.MethodsA total of 126 CTD patients with suspected infections who were hospitalized in the Department of Rheumatology, the Second Hospital of Shanxi Medical University from January 2020 to December 2021 were enrolled in this study. We retrospectively reviewed the results of mNGS and conventional diagnostic tests (CDTs).ResultsSystemic lupus erythematosus (SLE) and polymyositis/dermatomyositis (DM/PM) had the highest incidence of infections. The positive pathogen detection rates of mNGS were higher than those of CDT. The virus infections are the most common type in CTD patients with single or mixed infection, especially Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), and Human alphaherpesvirus 1. The incidence of prokaryote and eukaryote infections is secondary to viruses. Bloodstream infections of rare pathogens such as Pneumocystis jirovecii should be of concern. Meanwhile, the most common mixed infection was bacterial–virus coinfection.ConclusionmNGS has incremental application value in patients with CTD suspected of co-infection. It has a high sensitivity, and a wide detection range for microorganisms in CTD patients. Furthermore, the high incidence of opportunistic virus infections in CTD patients should be of sufficient concern.

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Section: Discussionmentioning

confidence: 99%

Application value of blood metagenomic next-generation sequencing in patients with connective tissue diseases

Yan

et al. 2022

Front. Immunol.

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“…The type of specimen, genome length, sequencing depth, and the throughput rate of the platform will affect the reads number in mNGS. We chose the reads per kilobase of transcript per million mapped reads (RPKM) as the normalization method for mNGS reads, based on the study by Liu et al (Liu et al, 2022c) and the sequencing characteristics of this study (single-end sequencing). RPKM was calculated using the formula: gene reads/[the total mapped reads (millions) × genome length (KB)].…”

Section: Statistical Analysis and Data Visualizationmentioning

confidence: 99%

Application of metagenomic next-generation sequencing in the diagnosis of pulmonary invasive fungal disease

Wang

You²,

Fu³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundMetagenomic next-generation sequencing (mNGS) is increasingly being used to detect pathogens directly from clinical specimens. However, the optimal application of mNGS and subsequent result interpretation can be challenging. In addition, studies reporting the use of mNGS for the diagnosis of invasive fungal infections (IFIs) are rare.ObjectiveWe critically evaluated the performance of mNGS in the diagnosis of pulmonary IFIs, by conducting a multicenter retrospective analysis. The methodological strengths of mNGS were recognized, and diagnostic cutoffs were determined.MethodsA total of 310 patients with suspected pulmonary IFIs were included in this study. Conventional microbiological tests (CMTs) and mNGS were performed in parallel on the same set of samples. Receiver operating characteristic (ROC) curves were used to evaluate the performance of the logarithm of reads per kilobase per million mapped reads [lg(RPKM)], and read counts were used to predict true-positive pathogens.ResultThe majority of the selected patients (86.5%) were immunocompromised. Twenty species of fungi were detected by mNGS, which was more than was achieved with standard culture methods. Peripheral blood lymphocyte and monocyte counts, as well as serum albumin levels, were significantly negatively correlated with fungal infection. In contrast, C-reactive protein and procalcitonin levels showed a significant positive correlation with fungal infection. ROC curves showed that mNGS [and especially lg(RPKM)] was superior to CMTs in its diagnostic performance. The area under the ROC curve value obtained for lg(RPKM) in the bronchoalveolar lavage fluid of patients with suspected pulmonary IFIs, used to predict true-positive pathogens, was 0.967, and the cutoff value calculated from the Youden index was −5.44.ConclusionsIn this study, we have evaluated the performance of mNGS-specific indicators that can identify pathogens in patients with IFIs more accurately and rapidly than CMTs, which will have important clinical implications.

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“…Standard microbiological blood cultures can have variable yields, long turnaround times, and low sensitivity, which contribute to inappropriate antibiotic therapy [ 13 ]. Metagenomic next-generation sequencing (mNGS) provides a sensitive and thorough approach that allows detection of pathogens in clinical samples regardless of whether they are viral, bacterial, fungal, or parasitic [ 14 ]. The detection approach of mNGS has become increasingly available to identify pathogens in cases of various diseases such as central nervous system infection [ 15 ], tuberculous meningitis [ 16 ], and severe pneumonia [ 17 ], showing better sensitivity and specificity than conventional methods.…”

Section: Introductionmentioning

confidence: 99%

Risk Factors and Outcome of Sepsis in Traumatic Patients and Pathogen Detection Using Metagenomic Next-Generation Sequencing

Tong

Zhang

et al. 2022

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Objective. Sepsis, a life-threatening clinical syndrome, is a leading cause of mortality after experiencing multiple traumas. Once diagnosed with sepsis, patients should be given an appropriate empiric antimicrobial treatment followed by the specific antibiotic therapy based on blood culture due to its rapid progression to tissue damage and organ failure. In this study, we aimed to analyze the risk factors and outcome of sepsis in traumatic patients and to investigate the performance of metagenomic next-generation sequencing (mNGS) compared with standard microbiological diagnostics in post-traumatic sepsis. Methods. The study included 528 patients with multiple traumas among which there were 142 cases with post-traumatic sepsis. Patients’ demographic and clinical data were recorded. The outcome measures included mortality during the emergency intensive care unit (EICU), EICU length of stay (LOS), all-cause 28-day mortality, and total ventilator days in 28 days after admission. A total of 89 blood samples from 89 septic patients underwent standard microbiological blood cultures and 89 samples of peripheral blood (n = 21), wound secretion (n = 41), bronchoalveolar lavage fluid (BALF) (19), ascites (n = 5), and sputum (n = 3) underwent mNGS. Pathogen detection was compared between standard microbiological blood cultures and mNGS. Results. The sepsis group and non-sepsis group exhibited significant differences regarding shock on admission, blood transfusion, mechanical ventilation, body temperature, heart rate, WBC count, neutrophil count, hematocrit, urea nitrogen, creatinine, CRP, D-D dimer, PCT, scores of APACHE II, sequential organ failure assessment (SOFA), and Injury Severity Score (ISS) on admission to the EICU, and Multiple Organ Dysfunction Syndromes (MODS) ( P < 0.05 ). Multivariate logistic regression analysis showed that scores of APACHE II, SOFA, and ISS on admission, and MODS were independent risk factors for the occurrence of sepsis in patients with multiple traumas. The 28-day mortality was higher in the sepsis group than in the non-sepsis group (45.07% vs. 19.17%, P < 0.001 ). The mortality during the EICU was higher in the sepsis group than in the non-sepsis group ( P = 0.002 ). The LOS in the EICU in the sepsis group was increased compared with the non-sepsis group ( P = 0.004 ). The total ventilator days in 28 days after admission in the sepsis group was increased compared with the non-sepsis group ( P < 0.001 ). Multivariate logistic regression analysis showed that septic shock, APACHE II score on admission, SOFA score, and MODS were independent risk factors of death for patients with post-traumatic sepsis. The positive detection rate of mNGS was 91.01% (81/89), which was significantly higher than that of standard microbiological blood cultures (39.33% (35/89)). Standard microbiological blood cultures and mNGS methods demonstrated double positive results in 33 (37.08%) specimens and double-negative results in 8 (8.99%) specimens, while 46 (51.69%) samples and 2 (2.25%) samples had positive results only with mNGS or culture alone, respectively. Conclusion. Our study identifies risk factors for the incidence and death of sepsis in traumatic patients and shows that mNGS may serve as a better diagnostic tool for the identification of pathogens in post-traumatic sepsis than standard microbiological blood cultures.

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Application of mNGS in the Etiological Analysis of Lower Respiratory Tract Infections and the Prediction of Drug Resistance

Abstract: LRTIs are caused by hundreds of pathogens, and they have become a great threat to human health due to the limitations of traditional etiological detection methods. As an unbiased approach to detect pathogens, mNGS overcomes such etiological diagnostic challenges.

Cited by 29 publications

References 26 publications

Application value of blood metagenomic next-generation sequencing in patients with connective tissue diseases

Application value of blood metagenomic next-generation sequencing in patients with connective tissue diseases

Application of metagenomic next-generation sequencing in the diagnosis of pulmonary invasive fungal disease

Risk Factors and Outcome of Sepsis in Traumatic Patients and Pathogen Detection Using Metagenomic Next-Generation Sequencing

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