|
|
mNGS技术在下呼吸道感染精准诊断中的运用与挑战
|
Abstract:
下呼吸道感染长期以来都是全球主要导致死亡的原因之一，并且随着感染多重耐药菌患者的比例增加，快速而又准确地明确致病微生物在治疗中变得至关重要。宏基因组二代测序的出现打破了传统检测方法的局限性，它能一次性检测出标本中已知或未知的细菌、真菌及病毒，为病原微生物的检测提供了一种更全面和精准的工具。目前宏基因组二代测序已广泛运用于临床中，虽然它在使用中还面临着一些挑战和局限性，但其在感染性疾病的诊断中展现出的独特优势，使其成为一种极具潜力的技术工具。
Lower respiratory tract infections have long been one of the leading causes of mortality worldwide. With the increasing proportion of patients infected with multidrug-resistant pathogens, rapidly and accurately identifying causative microorganisms has become crucial in treatment. The advent of metagenomic next-generation sequencing (mNGS) has overcome the limitations of traditional detection methods, enabling the simultaneous identification of known and unknown bacteria, fungi, and viruses in a single sample, providing a more comprehensive and precise tool for pathogen detection. Currently, mNGS has been widely applied in clinical practice. Despite facing certain challenges and limitations in its implementation, its unique advantages in diagnosing infectious diseases make it an exceptionally promising technological tool.
| [1] | Naghavi, M., Ong, K.L., Aali, A., Ababneh, H.S., Abate, Y.H., Abbafati, C., et al. (2024) Global Burden of 288 Causes of Death and Life Expectancy Decomposition in 204 Countries and Territories and 811 Subnational Locations, 1990-2021: A Systematic Analysis for the Global Burden of Disease Study 2021. The Lancet, 403, 2100-2132. https://doi.org/10.1016/s0140-6736(24)00367-2 |
| [2] | Magill, S.S., Edwards, J.R., Bamberg, W., Beldavs, Z.G., Dumyati, G., Kainer, M.A., et al. (2014) Multistate Point-Prevalence Survey of Health Care-Associated Infections. New England Journal of Medicine, 370, 1198-1208. https://doi.org/10.1056/nejmoa1306801 |
| [3] | Murray, C.J.L., Ikuta, K.S., Sharara, F., Swetschinski, L., Robles Aguilar, G., Gray, A., et al. (2022) Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. The Lancet, 399, 629-655. https://doi.org/10.1016/s0140-6736(21)02724-0 |
| [4] | Miao, Q., Ma, Y., Wang, Q., Pan, J., Zhang, Y., Jin, W., et al. (2018) Microbiological Diagnostic Performance of Metagenomic Next-Generation Sequencing When Applied to Clinical Practice. Clinical Infectious Diseases, 67, S231-S240. https://doi.org/10.1093/cid/ciy693 |
| [5] | Cheng, M.P., Stenstrom, R., Paquette, K., Stabler, S.N., Akhter, M., Davidson, A.C., et al. (2019) Blood Culture Results before and after Antimicrobial Administration in Patients with Severe Manifestations of Sepsis: A Diagnostic Study. Annals of Internal Medicine, 171, 547-554. https://doi.org/10.7326/m19-1696 |
| [6] | Hendriksen, R.S., Bortolaia, V., Tate, H., Tyson, G.H., Aarestrup, F.M. and McDermott, P.F. (2019) Using Genomics to Track Global Antimicrobial Resistance. Frontiers in Public Health, 7, Article 242. https://doi.org/10.3389/fpubh.2019.00242 |
| [7] | Qian, Y., Wang, H., Zhou, Y., Zhang, H., Zhu, Y., Zhou, X., et al. (2021) Improving Pulmonary Infection Diagnosis with Metagenomic Next Generation Sequencing. Frontiers in Cellular and Infection Microbiology, 10, Article 567615. https://doi.org/10.3389/fcimb.2020.567615 |
| [8] | Zhou, J., Ding, W., Liu, Y., Gao, Y., Xu, L., Geng, R., et al. (2022) Diagnostic Value of Metagenomic Next-Generation Sequencing for Pulmonary Infection in Intensive Care Unit and Non-Intensive Care Unit Patients. Frontiers in Cellular and Infection Microbiology, 12, Article 929856. https://doi.org/10.3389/fcimb.2022.929856 |
| [9] | Ju, C., Lian, Q., Guan, W., Chen, A., Zhang, J., Xu, X., et al. (2022) Metagenomic Next-Generation Sequencing for Diagnosing Infections in Lung Transplant Recipients: A Retrospective Study. Transplant International, 36, Article 10265. https://doi.org/10.3389/ti.2022.10265 |
| [10] | Chen, T., Zhang, L., Huang, W., Zong, H., Li, Q., Zheng, Y., et al. (2023) Detection of Pathogens and Antimicrobial Resistance Genes in Ventilator-Associated Pneumonia by Metagenomic Next-Generation Sequencing Approach. Infection and Drug Resistance, 16, 923-936. https://doi.org/10.2147/idr.s397755 |
| [11] | Lv, T., Zhao, Q., Liu, J., Wang, S., Wu, W., Miao, L., et al. (2024) Utilizing Metagenomic Next-Generation Sequencing for Pathogen Detection and Diagnosis in Lower Respiratory Tract Infections in Real-World Clinical Practice. Infection, 52, 625-636. https://doi.org/10.1007/s15010-024-02185-1 |
| [12] | Zhong, J., Liu, Y., Luo, N., Wei, Q., Su, Q., Zou, J., et al. (2023) Metagenomic Next-Generation Sequencing for Rapid Detection of Pulmonary Infection in Patients with Acquired Immunodeficiency Syndrome. Annals of Clinical Microbiology and Antimicrobials, 22, Article No. 57. https://doi.org/10.1186/s12941-023-00608-9 |
| [13] | Dong, Y., Chen, Q., Tian, B., Li, J., Li, J. and Hu, Z. (2023) Advancing Microbe Detection for Lower Respiratory Tract Infection Diagnosis and Management with Metagenomic Next-Generation Sequencing. Infection and Drug Resistance, 16, 677-694. https://doi.org/10.2147/idr.s387134 |
| [14] | Liang, W., Zhang, Q., Qian, Q., Wang, M., Ding, Y., Zhou, J., et al. (2024) Diagnostic Strategy of Metagenomic Next-Generation Sequencing for Gram Negative Bacteria in Respiratory Infections. Annals of Clinical Microbiology and Antimicrobials, 23, Article No. 10. https://doi.org/10.1186/s12941-024-00670-x |
| [15] | Liu, X., Chen, Y., Ouyang, H., Liu, J., Luo, X., Huang, Y., et al. (2021) Tuberculosis Diagnosis by Metagenomic Next-Generation Sequencing on Bronchoalveolar Lavage Fluid: A Cross-Sectional Analysis. International Journal of Infectious Diseases, 104, 50-57. https://doi.org/10.1016/j.ijid.2020.12.063 |
| [16] | Deng, W., Xu, H., Wu, Y. and Li, J. (2022) Diagnostic Value of Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing in Pediatric Pneumonia. Frontiers in Cellular and Infection Microbiology, 12, Article 950531. https://doi.org/10.3389/fcimb.2022.950531 |
| [17] | Fang, X., Mei, Q., Fan, X., Zhu, C., Yang, T., Zhang, L., et al. (2020) Diagnostic Value of Metagenomic Next-Generation Sequencing for the Detection of Pathogens in Bronchoalveolar Lavage Fluid in Ventilator-Associated Pneumonia Patients. Frontiers in Microbiology, 11, Article 599756. https://doi.org/10.3389/fmicb.2020.599756 |
| [18] | Qu, J., Zhang, J., Chen, Y., Huang, Y., Xie, Y., Zhou, M., et al. (2022) Aetiology of Severe Community Acquired Pneumonia in Adults Identified by Combined Detection Methods: A Multi-Centre Prospective Study in China. Emerging Microbes & Infections, 11, 556-566. https://doi.org/10.1080/22221751.2022.2035194 |
| [19] | 符蓉, 林韧, 范志平, 等. 宏基因组二代测序在异基因造血干细胞移植后耶氏肺孢子菌肺炎诊断中的意义[J]. 中华血液学杂志, 2024, 45(1): 62-67. https://rs.yiigle.com/cmaid/1496598 |
| [20] | Chen, Y., Feng, W., Ye, K., Guo, L., Xia, H., Guan, Y., et al. (2021) Application of Metagenomic Next-Generation Sequencing in the Diagnosis of Pulmonary Infectious Pathogens from Bronchoalveolar Lavage Samples. Frontiers in Cellular and Infection Microbiology, 11, Article 541092. https://doi.org/10.3389/fcimb.2021.541092 |
| [21] | Azoulay, E., Russell, L., Van de Louw, A., Metaxa, V., Bauer, P., Povoa, P., et al. (2020) Diagnosis of Severe Respiratory Infections in Immunocompromised Patients. Intensive Care Medicine, 46, 298-314. https://doi.org/10.1007/s00134-019-05906-5 |
| [22] | Liu, Y., Wu, W., Xiao, Y., Zou, H., Hao, S. and Jiang, Y. (2024) Application of Metagenomic Next-Generation Sequencing and Targeted Metagenomic Next-Generation Sequencing in Diagnosing Pulmonary Infections in Immunocompetent and Immunocompromised Patients. Frontiers in Cellular and Infection Microbiology, 14, Article 1439472. https://doi.org/10.3389/fcimb.2024.1439472 |
| [23] | Maini, R., Henderson, K.L., Sheridan, E.A., Lamagni, T., Nichols, G., Delpech, V., et al. (2013) Increasing Pneumocystis Pneumonia, England, UK, 2000-2010. Emerging Infectious Diseases, 19, 386-392. https://doi.org/10.3201/eid1903.121151 |
| [24] | 李晓琴, 杨彩丽, 毛玉环, 等. 宏基因组二代测序用于艾滋病患者中耶氏肺孢子菌感染的诊断价值[J]. 中华检验医学杂志, 2023, 46(2): 169-175. https://rs.yiigle.com/cmaid/1447189 |
| [25] | Tan, Y., Chen, Z., Zeng, Z., Wu, S., Liu, J., Zou, S., et al. (2023) Microbiomes Detected by Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing among HIV-Infected and Uninfected Patients with Pulmonary Infection. Microbiology Spectrum, 11, e00005-23. https://doi.org/10.1128/spectrum.00005-23 |
| [26] | Xie, Y., Dai, B., Zhou, X., Liu, H., Wu, W., Yu, F., et al. (2023) Diagnostic Value of Metagenomic Next-Generation Sequencing for Multi-Pathogenic Pneumonia in HIV-Infected Patients. Infection and Drug Resistance, 16, 607-618. https://doi.org/10.2147/idr.s394265 |
| [27] | Zhuang, L., Zhu, C., Ma, J., Zhu, D., Zhu, H., Zhong, S., et al. (2024) Predictive Performance of Metagenomic Next Generation Sequencing in Early Detection of Post-Liver Transplantation Infections. Heliyon, 10, e36405. https://doi.org/10.1016/j.heliyon.2024.e36405 |
| [28] | Fu, R., Xu, J., Fan, Z., Qu, H., Jiang, Y., Xiong, W., et al. (2024) Metagenomic Next-Generation Sequencing in the Diagnosis of Pulmonary Infections after Allogeneic Hematopoietic Stem Cell Transplantation. Transplantation and Cellular Therapy, 30, 1110.e1-1110.e10. https://doi.org/10.1016/j.jtct.2024.08.014 |
| [29] | Zhang, X., Wang, F., Yu, J. and Jiang, Z. (2023) Clinical Application Value of Metagenomic Second-Generation Sequencing Technology in Hematologic Diseases with and without Transplantation. Frontiers in Cellular and Infection Microbiology, 13, Article 1135460. https://doi.org/10.3389/fcimb.2023.1135460 |
| [30] | Qu, Y., Ding, W., Liu, S., Wang, X., Wang, P., Liu, H., et al. (2022) Metagenomic Next-Generation Sequencing vs. Traditional Pathogen Detection in the Diagnosis of Infection after Allogeneic Hematopoietic Stem Cell Transplantation in Children. Frontiers in Microbiology, 13, Article 868160. https://doi.org/10.3389/fmicb.2022.868160 |
| [31] | Zhu, N., Zhang, D., Wang, W., Li, X., Yang, B., Song, J., et al. (2020) A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine, 382, 727-733. https://doi.org/10.1056/nejmoa2001017 |
| [32] | Cillóniz, C., Torres, A., Niederman, M., van der Eerden, M., Chalmers, J., Welte, T., et al. (2016) Community-Acquired Pneumonia Related to Intracellular Pathogens. Intensive Care Medicine, 42, 1374-1386. https://doi.org/10.1007/s00134-016-4394-4 |
| [33] | Wen, S., Zeng, J. and Li, Y. (2024) Rickettsia Felis Pulmonary Infection Detected via Metagenomic Next-Generation Sequencing in a Clonorchiasis Patient: A Case Report. Infection and Drug Resistance, 17, 5189-5194. https://doi.org/10.2147/idr.s481950 |
| [34] | Ni, L., Wu, Z. and Huang, J. (2024) Detection of Pulmonary Actinomycosis by Metagenomic Next-Generation Sequencing in a Cancer Patient Receiving Maintenance Olaparib: A Review and Case Report. Respiratory Medicine Case Reports, 48, Article 102007. https://doi.org/10.1016/j.rmcr.2024.102007 |
| [35] | Li, Y., Li, Q., Lei, H., Wei, X., Feng, T., Qin, H., et al. (2024) Co-Infection with Nocardia Terpene and Pneumocystis Jirovecii in a Patient with Anti-Synthetase Syndrome: A Case Report. Infection and Drug Resistance, 17, 3777-3783. https://doi.org/10.2147/idr.s474836 |
| [36] | Jiang, Y., Tian, R., Zhang, C., Zhang, L., Cui, X. and Wang, P. (2024) Diagnosis and Treatment of a Patient with Pulmonary Infection Caused by Emergomyces orientalis: A Case Report. Future Microbiology, 19, 1195-1202. https://doi.org/10.1080/17460913.2024.2366653 |
| [37] | Li, K., Zhang, Y., Zhang, D., Chen, Q. and Fang, X. (2024) Case Report: Systemic Multi-Organ Involvement in an Adult-Onset Immunodeficiency Patient Infected with Talaromyces marneffei. Frontiers in Immunology, 15, Article 1430179. https://doi.org/10.3389/fimmu.2024.1430179 |
| [38] | Tao, L.-L., Hu, B.-J., He, L.-X., Wei, L., Xie, H.-M., Wang, B.-Q., et al. (2012) Etiology and Antimicrobial Resistance of Community-Acquired Pneumonia in Adult Patients in China. Chinese Medical Journal, 125, 2967-2972. |
| [39] | Chung, D.R., Song, J., Kim, S.H., Thamlikitkul, V., Huang, S., Wang, H., et al. (2011) High Prevalence of Multidrug-Resistant Nonfermenters in Hospital-Acquired Pneumonia in Asia. American Journal of Respiratory and Critical Care Medicine, 184, 1409-1417. https://doi.org/10.1164/rccm.201102-0349oc |
| [40] | 中华医学会呼吸病学分会感染学组. 中国成人医院获得性肺炎与呼吸机相关性肺炎诊断和治疗指南(2018年版) [J]. 中华结核和呼吸杂志, 2018, 41(4): 255-280. https://rs.yiigle.com/cmaid/1036232 |
| [41] | Hong, L., Chen, Y. and Ye, L. (2021) Characteristics of the Lung Microbiota in Lower Respiratory Tract Infections with and without History of Pneumonia. Bioengineered, 12, 10480-10490. https://doi.org/10.1080/21655979.2021.1997563 |
| [42] | Wang, J., Zhu, Y., Mo, Q. and Yang, Y. (2022) Case Report: A Chlamydia Psittaci Pulmonary Infection Presenting with Migratory Infiltrates. Frontiers in Public Health, 10, Article 1028989. https://doi.org/10.3389/fpubh.2022.1028989 |
| [43] | Zhang, B., Gui, R., Wang, Q., Jiao, X., Li, Z., Wang, J., et al. (2022) Comparing the Application of mNGS after Combined Pneumonia in Hematologic Patients Receiving Hematopoietic Stem Cell Transplantation and Chemotherapy: A Retrospective Analysis. Frontiers in Cellular and Infection Microbiology, 12, Article 969126. https://doi.org/10.3389/fcimb.2022.969126 |
| [44] | Yang, T., Mei, Q., Fang, X., Zhu, S., Wang, Y., Li, W., et al. (2022) Clinical Value of Metagenomics Next-Generation Sequencing in Bronchoalveolar Lavage Fluid for Patients with Severe Hospital-Acquired Pneumonia: A Nested Case-Control Study. Infection and Drug Resistance, 15, 1505-1514. https://doi.org/10.2147/idr.s356662 |
| [45] | Liu, H., Zhang, Y., Yang, J., Liu, Y. and Chen, J. (2022) Application of mNGS in the Etiological Analysis of Lower Respiratory Tract Infections and the Prediction of Drug Resistance. Microbiology Spectrum, 10, e02502-21. https://doi.org/10.1128/spectrum.02502-21 |
| [46] | 中华医学会呼吸病学分会. 下呼吸道感染宏基因组二代测序报告临床解读路径专家共识[J]. 中华结核和呼吸杂志, 2023, 46(4): 322-335. https://rs.yiigle.com/cmaid/1446380 |
| [47] | Diao, Z., Han, D., Zhang, R. and Li, J. (2022) Metagenomics Next-Generation Sequencing Tests Take the Stage in the Diagnosis of Lower Respiratory Tract Infections. Journal of Advanced Research, 38, 201-212. https://doi.org/10.1016/j.jare.2021.09.012 |
| [48] | Wang, K., Li, P., Lin, Y., Chen, H., Yang, L., Li, J., et al. (2020) Metagenomic Diagnosis for a Culture-Negative Sample from a Patient with Severe Pneumonia by Nanopore and Next-Generation Sequencing. Frontiers in Cellular and Infection Microbiology, 10, Article 182. https://doi.org/10.3389/fcimb.2020.00182 |
| [49] | Hao, J., Li, W., Wang, Y., Zhao, J. and Chen, Y. (2023) Clinical Utility of Metagenomic Next-Generation Sequencing in Pathogen Detection for Lower Respiratory Tract Infections and Impact on Clinical Outcomes in Southernmost China. Frontiers in Cellular and Infection Microbiology, 13, Article 1271952. https://doi.org/10.3389/fcimb.2023.1271952 |
| [50] | Chen, H., Bai, X., Gao, Y., Liu, W., Yao, X. and Wang, J. (2021) Profile of Bacteria with ARGs among Real-World Samples from ICU Admission Patients with Pulmonary Infection Revealed by Metagenomic NGS. Infection and Drug Resistance, 14, 4993-5004. https://doi.org/10.2147/idr.s335864 |
| [51] | Zhu, L., Xu, H., Pu, Y., Fu, C., Pan, Q. and Zhao, H. (2023) Case Report: Comprehensive Management of Pneumocystis Jiroveci Pneumonia (PJP) and Secondary Infections of Multiple-Drug Resistant Enterobacter cloacae complex and Pseudomonas aeruginosa in a Kidney Transplant Recipient with Sulfonamide Allergies. Infection and Drug Resistance, 16, 6185-6193. https://doi.org/10.2147/idr.s428890 |
| [52] | Lin, L., Zhang, R., Zhang, Z., Chang, Y., Lin, R., Dou, H., et al. (2023) Clinical Value of Metagenomics Next-Generation Sequencing in Antibiotic Resistance of a Patient with Severe Refractory Mycoplasma Pneumoniae Pneumonia: A Case Report. Infection and Drug Resistance, 16, 4593-4597. https://doi.org/10.2147/idr.s419873 |
| [53] | Zheng, Y., Liu, W., Xiao, T., Chen, H. and Liu, Y. (2024) Clinical Utility of Metagenomic Next-Generation Sequencing on Bronchoalveolar Lavage Fluid in Diagnosis of Lower Respiratory Tract Infections. BMC Pulmonary Medicine, 24, Article No. 422. https://doi.org/10.1186/s12890-024-03237-w |
| [54] | Zhan, S., Li, S., Cao, Y., Liu, D. and Feng, J. (2024) Value of Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing in Acute Exacerbation of Fibrosing Interstitial Lung Disease: An Individualized Treatment Protocol Based on Microbiological Evidence. BMC Pulmonary Medicine, 24, Article No. 400. https://doi.org/10.1186/s12890-024-03216-1 |
