Exploring the Clinical Utility of Metagenomic Next-Generation Sequencing in the Diagnosis of Pulmonary Infection

Xie, Guijuan; Zhao, Bo; Wang, Xun; Bao, Lei; Xu, Yiming; Ren, Xian; Ji, Jiali; He, Ting; Zhao, Hongqing

doi:10.1007/s40121-021-00476-w

Cited by 42 publications

(35 citation statements)

References 45 publications

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“…Xie found that the most common co-infection was bacterial and fungal mixed infection, followed by bacterial and bacterial infection. 40 Wang found that the most common mixed pulmonary infection was virus and fungal mixed infection. 39 Legoff found that the most common mixed infection was bacterial and viral mixed infection.…”

Section: Discussionmentioning

confidence: 99%

Clinical Application and Evaluation of Metagenomic Next-Generation Sequencing in Pulmonary Infection with Pleural Effusion

Xu¹,

Hu²,

Wang³

et al. 2022

IDR

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Purpose Metagenomic next-generation sequencing (mNGS) is a novel technique of pathogens detection that plays an increasingly important role in clinical practice. In this study, we explored the application value of mNGS in pulmonary infection combined with pleural effusion applied to samples of pleural effusion fluid. Patients and Methods We reviewed 80 cases of pulmonary infection with pleural effusion between August 2020 and October 2021. Among them, 40 patients were placed in the mNGS group and underwent both culture and mNGS testing; the patients in the control group were only subjected to culture test. The effectiveness of mNGS was evaluated for microbial composition and diagnostic accuracy in every pleural effusion specimen type. Results We found that the positive rate of mNGS was 70% (28/40). The comparison between mNGS and culture method resulted that the sensitivity was 100% (95% CI: 29.2–100%) and the specificity was 64.9% (95% CI: 47.5–79.8%). The positive predictive value of mNGS was 18.8% (95% CI, 13.0–26.3%), and the negative predictive value was 100%. The most commonly identified potential pathogens were bacteria, such as Streptococcus , Prevotella , Parvimonas , Porphyromonas and Gemella . The most detected fungal infection was Candida and Pneumocystis . A total of 11 patients were identified as mixed infection by mNGS. Treatment regimen adjustments were made according to mNGS results and the overall length of hospital stay in the mNGS group was shorter compared to that of the control group. Conclusion In this study, mNGS produced higher positive rates than the culture method in detecting pathogens in the pleural effusion specimens. The technology performed satisfactorily, providing more diagnostic evidence and reducing the length of hospital stay.

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Section: Discussionmentioning

confidence: 99%

Clinical Application and Evaluation of Metagenomic Next-Generation Sequencing in Pulmonary Infection with Pleural Effusion

Xu¹,

Hu²,

Wang³

et al. 2022

IDR

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“…Based on high-throughput sequencing, metagenomic next-generation sequencing (mNGS) is thought to be a promising microbial identification technology because of its rapid cycles and high sensitivity. mNGS identifies and classifies a wide range of pathogens (including respiratory tract ( Xie et al., 2021 ), blood stream ( Jing et al., 2021 ), central nervous system ( Wilson et al., 2019 ), and prosthetic joints pathogens ( Thoendel et al., 2018 )), and is a widely used microbial test for infectious diseases, particularly for special and rare pathogens. It can also be used to analyze drug resistance genes and virulence factors in pathogens.…”

Section: Introductionmentioning

confidence: 99%

Metagenomic next-generation sequencing for the diagnosis of pulmonary aspergillosis in non-neutropenic patients: a retrospective study

Bao¹,

Song²,

Chen³

et al. 2022

Front. Cell. Infect. Microbiol.

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This study aimed to obtain further in-depth information on the value of metagenomic next-generation sequencing (mNGS) for diagnosing pulmonary aspergillosis in non-neutropenic patients. We did a retrospective study, in which 33 non-neutropenic patients were included, of which 12 were patients with pulmonary aspergillosis and 21 were diagnosed with non-pulmonary aspergillosis. Fungi and all other co-pathogens in bronchoalveolar lavage fluid (BALF) (27 cases), blood (6 cases), and/or pleural fluid (1 case) samples were analyzed using mNGS. One of the patients submitted both BALF and blood samples. We analyzed the clinical characteristics, laboratory tests, and radiologic features of pulmonary aspergillosis patients and compared the diagnostic accuracy, including sensitivity, specificity, positive predictive value, and negative predictive value of mNGS with conventional etiological methods and serum (1,3)-β-D-glucan. We also explored the efficacy of mNGS in detecting mixed infections and co-pathogens. We further reviewed modifications of antimicrobial therapy for patients with pulmonary aspergillosis according to the mNGS results. Finally, we compared the detection of Aspergillus in BALF and blood samples from three patients using mNGS. In non-neutropenic patients, immunocompromised conditions of non-pulmonary aspergillosis were far less prevalent than in patients with pulmonary aspergillosis. More patients with pulmonary aspergillosis received long-term systemic corticosteroids (50% vs. 14.3%, p < 0.05). Additionally, mNGS managed to reach a sensitivity of 91.7% for diagnosing pulmonary aspergillosis, which was significantly higher than that of conventional etiological methods (33.3%) and serum (1,3)-β-D-glucan (33.3%). In addition, mNGS showed superior performance in discovering co-pathogens (84.6%) of pulmonary aspergillosis; bacteria, bacteria-fungi, and bacteria-PJP-virus were most commonly observed in non-neutropenic patients. Moreover, mNGS results can help guide effective treatments. According to the mNGS results, antimicrobial therapy was altered in 91.7% of patients with pulmonary aspergillosis. The diagnosis of Aspergillus detected in blood samples, which can be used as a supplement to BALF samples, seemed to show a higher specificity than that in BALF samples. mNGS is a useful and effective method for the diagnosis of pulmonary aspergillosis in non-neutropenic patients, detection of co-pathogens, and adjustment of antimicrobial treatment.

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“…However, in respiratory samples (e.g., sputum, BAL), many attempts remain in the verification phase due to the complex microbial community. Meanwhile, the detection performance of mNGS in pneumonia is not completely consistent in multiple studies [ 17 , 27 , 32 , 33 ]. Thus, although mNGS may have great potential for broad-spectrum surveillance or as a universal pathogen detection method, the results of mNGS should be interpreted with caution.…”

Section: Discussionmentioning

confidence: 93%

“…Miao et al reported that mNGS is not better than culture in recognizing bacteria but has superior feasibility in detecting fungi [ 28 ]. However, some studies reported inconsistent conclusions [ 17 , 34 , 35 ]. Possible explanations for this divergence are due to different sample types and some different test conditions of mNGS and culture.…”

Section: Discussionmentioning

confidence: 99%

“…The inclusion criteria were as follows: (1) patients who were diagnosed with pneumonia; (2) respiratory samples and detection process passed quality control for mNGS. The exclusion criteria were as follows: (1) patients who refused to undergo the mNGS examination and (2) patients without clinical data [ 17 ]. Pneumonia was diagnosed based on a composite reference standard based on the diagnostic criteria of community-acquired pneumonia (CAP) [ 18 ] and hospital-acquired pneumonia (HAP) [ 19 ].…”

Section: Study Design and Methodsmentioning

confidence: 99%

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Enhanced DNA and RNA pathogen detection via metagenomic sequencing in patients with pneumonia

Fang

Shi

et al. 2022

J Transl Med

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Background Metagenomic next-generation sequencing (mNGS) is an important supplement to conventional tests for pathogen detections of pneumonia. However, mNGS pipelines were limited by irregularities, high proportion of host nucleic acids, and lack of RNA virus detection. Thus, a regulated pipeline based on mNGS for DNA and RNA pathogen detection of pneumonia is essential. Methods We performed a retrospective study of 151 patients with pneumonia. Three conventional tests, culture, loop-mediated isothermal amplification (LAMP) and viral quantitative real-time polymerase chain reaction (qPCR) were conducted according to clinical needs, and all samples were detected using our optimized pipeline based on the mNGS (DNA and RNA) method. The performances of mNGS and three other tests were compared. Human DNA depletion was achieved respectively by MolYsis kit and pre-treatment using saponin and Turbo DNase. Three RNA library preparation methods were used to compare the detection performance of RNA viruses. Results An optimized mNGS workflow was built, which had only 1-working-day turnaround time. The proportion of host DNA in the pre-treated samples decreased from 99 to 90% and microbiome reads achieved an approximately 20-fold enrichment compared with those without host removal. Meanwhile, saponin and Turbo DNase pre-treatment exhibited an advantage for DNA virus detection compared with MolYsis. Besides, our in-house RNA library preparation procedure showed a more robust RNA virus detection ability. Combining three conventional methods, 76 (76/151, 50.3%) cases had no clear causative pathogen, but 24 probable pathogens were successfully detected in 31 (31/76 = 40.8%) unclear cases using mNGS. The agreement of the mNGS with the culture, LAMP, and viral qPCR was 60%, 82%, and 80%, respectively. Compared with all conventional tests, mNGS had a sensitivity of 70.4%, a specificity of 72.7%, and an overall agreement of 71.5%. Conclusions A complete and effective mNGS workflow was built to provide timely DNA and RNA pathogen detection for pneumonia, which could effectively remove the host sequence, had a higher microbial detection rate and a broader spectrum of pathogens (especially for viruses and some pathogens that are difficult to culture). Despite the advantages, there are many challenges in the clinical application of mNGS, and the mNGS report should be interpreted with caution.

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Exploring the Clinical Utility of Metagenomic Next-Generation Sequencing in the Diagnosis of Pulmonary Infection

Cited by 42 publications

References 45 publications

Clinical Application and Evaluation of Metagenomic Next-Generation Sequencing in Pulmonary Infection with Pleural Effusion

Clinical Application and Evaluation of Metagenomic Next-Generation Sequencing in Pulmonary Infection with Pleural Effusion

Metagenomic next-generation sequencing for the diagnosis of pulmonary aspergillosis in non-neutropenic patients: a retrospective study

Enhanced DNA and RNA pathogen detection via metagenomic sequencing in patients with pneumonia

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