Department of Respiratory Medicine, The Second Clinical Medical School of Nanjing Medical Universitygrid.89957.3a, Nanjing, Jiangsu, China.
Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Nanjing Medical Universitygrid.89957.3a, Nanjing, Jiangsu, China.
Microbiol Spectr. 2022 Aug 31;10(4):e0247321. doi: 10.1128/spectrum.02473-21. Epub 2022 Aug 9.
Metagenomic next-generation sequencing (mNGS) has been gradually applied to clinical practice due to its unbiased characteristics of pathogen detection. However, its diagnostic performance and clinical value in suspected pulmonary infection need to be evaluated. We systematically reviewed the clinical data of 246 patients with suspected pulmonary infection from 4 medical institutions between January 2019 and September 2021. The diagnostic performances of mNGS and conventional testing (CT) were systematically analyzed based on bronchoalveolar lavage fluid (BALF). The impacts of mNGS and CT on diagnosis modification and treatment adjustment were also assessed. The positive rates of mNGS and CT were 47.97% and 23.17%, respectively. The sensitivity of mNGS was significantly higher than that of CT (53.49% versus 23.26%, < 0.01), especially for infections of Mycobacterium tuberculosis (67.86% versus 17.86%, < 0.01), atypical pathogens (100.00% versus 7.14%, < 0.01), viruses (92.31% versus 7.69%, < 0.01), and fungi (78.57% versus 39.29%, < 0.01). The specificity of mNGS was superior to that of CT, with no statistical difference (90.32% versus 77.42%, = 0.167). The positive predictive value (PPV) and negative predictive value (NPV) of mNGS were 97.46% and 21.88%, respectively. Diagnosis modification and treatment adjustment were conducted in 32 (32/246, 13.01%) and 23 (23/246, 9.35%) cases, respectively, according to mNGS results only. mNGS significantly improved the diagnosis of suspected pulmonary infection, especially infections of M. tuberculosis, atypical pathogens, viruses, and fungi, and it demonstrated the pathogen distribution of pulmonary infections. It is expected to be a promising microbiological detection and diagnostic method in clinical practice. Pulmonary infection is a heterogeneous and complex infectious disease with high morbidity and mortality worldwide. In clinical practice, a considerable proportion of the etiology of pulmonary infection is unclear, microbiological diagnosis being challenging. Metagenomic next-generation sequencing detects all nucleic acids in a sample in an unbiased manner, revealing the microbial community environment and organisms and improving the microbiological detection and diagnosis of infectious diseases in clinical settings. This study is the first multicenter, large-scale retrospective study based entirely on BALF for pathogen detection by mNGS, and it demonstrated the superior performance of mNGS for microbiological detection and diagnosis of suspected pulmonary infection, especially in infections of Mycobacterium tuberculosis, atypical pathogens, viruses, and fungi. It also demonstrated the pathogen distribution of pulmonary infections in the real world, guiding targeted treatment and improving clinical management and prognoses.
基于宏基因组下一代测序(mNGS)在病原体检测方面具有无偏倚的特点,其已逐渐应用于临床实践。然而,其在疑似肺部感染中的诊断性能和临床价值仍需要评估。我们系统地回顾了 2019 年 1 月至 2021 年 9 月期间 4 家医疗机构的 246 例疑似肺部感染患者的临床数据。我们基于支气管肺泡灌洗液(BALF),系统地分析了 mNGS 和常规检测(CT)的诊断性能。还评估了 mNGS 和 CT 对诊断修正和治疗调整的影响。mNGS 和 CT 的阳性率分别为 47.97%和 23.17%。mNGS 的灵敏度明显高于 CT(53.49%比 23.26%,<0.01),尤其是结核分枝杆菌(67.86%比 17.86%,<0.01)、非典型病原体(100.00%比 7.14%,<0.01)、病毒(92.31%比 7.69%,<0.01)和真菌(78.57%比 39.29%,<0.01)感染。mNGS 的特异性优于 CT,但无统计学差异(90.32%比 77.42%,=0.167)。mNGS 的阳性预测值(PPV)和阴性预测值(NPV)分别为 97.46%和 21.88%。仅根据 mNGS 结果,分别有 32 例(32/246,13.01%)和 23 例(23/246,9.35%)进行了诊断修正和治疗调整。mNGS 显著提高了疑似肺部感染的诊断,特别是结核分枝杆菌、非典型病原体、病毒和真菌感染的诊断,并且揭示了肺部感染的病原体分布。预计它将成为临床实践中一种有前途的微生物检测和诊断方法。
肺部感染是一种异质性和复杂的传染病,在全球范围内发病率和死亡率都很高。在临床实践中,相当一部分肺部感染的病因不明,微生物学诊断具有挑战性。宏基因组下一代测序以无偏倚的方式检测样本中的所有核酸,揭示微生物群落环境和生物体,从而改善临床环境中传染病的微生物学检测和诊断。本研究是第一项完全基于 BALF 进行病原体检测的多中心、大规模回顾性研究,它证明了 mNGS 在疑似肺部感染的微生物学检测和诊断方面具有优越的性能,特别是在结核分枝杆菌、非典型病原体、病毒和真菌感染方面。它还证明了真实世界中肺部感染的病原体分布,指导了靶向治疗,改善了临床管理和预后。
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