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Abstract：
BACKGROUND: The emergence of metagenomic next-generation sequencing (mNGS) may provide a promising tool for early and comprehensive identification of the causative pathogen in community-acquired pneumonia (CAP). In this study, we aim to further evaluate the etiological diagnostic value of mNGS in suspected CAP.
METHODS: A total of 555 bronchoalveolar lavage fluid (BALF) samples were collected for pathogen detection by mNGS from 541 patients with suspected CAP. The clinical value was assessed based on infection diagnosis and treatment guidance. The diagnostic performance for pathogen identification by mNGS and sputum culture and for tuberculosis (TB) by mNGS and X-pert MTB/RIF were compared. To evaluate the potential for treatment guidance, we analyzed the treatment regimen of patients with suspected CAP, including imaging changes of lung after empirical antibacterial therapy, intensified regimen, antifungal treatment, and a 1-year follow up for patients with unconfirmed diagnosis and non-improvement imaging after anti-infective treatment and patients with high suspicion of TB or NTM infection who were transferred to the Wuhan Pulmonary Hospital for further diagnosis and even anti-mycobacterium therapy.
RESULTS: Of the 516 BALF samples that were analyzed by both mNGS and sputum culture, the positivity rate of mNGS was significantly higher than that of sputum culture (79.1% vs. 11.4%, P = 0.001). A total of 48 samples from patients with confirmed TB were analyzed by both mNGS and X-pert MTB/RIF, and the sensitivity of mNGS for the diagnosis of active TB was significantly lower than that of X-pert MTB/RIF (64.6% vs. 85.4%, P = 0.031). Of the 106 pathogen-negative cases, 48 were ultimately considered non-infectious diseases, with a negative predictive value of 45.3%. Of the 381 pathogen-positive cases, 311 were eventually diagnosed as CAP, with a positive predictive value of 81.6%. A total of 487 patients were included in the evaluation of the therapeutic effect, and 67.1% improved with initial empirical antibiotic treatment. Of the 163 patients in which bacteria were detected, 77.9% improved with antibacterial therapy; of the 85 patients in which fungi were detected, 12.9% achieved remission after antifungal therapy.
CONCLUSIONS: Overall, mNGS had unique advantages in the detection of suspected CAP pathogens. However, mNGS was not superior to X-pert MTB/RIF for the diagnosis of TB. In addition, mNGS was not necessary as a routine test for all patients admitted with suspected CAP. Furthermore, when fungi are detected by mNGS, antifungal therapy should be cautious.
METHODS: A total of 555 bronchoalveolar lavage fluid (BALF) samples were collected for pathogen detection by mNGS from 541 patients with suspected CAP. The clinical value was assessed based on infection diagnosis and treatment guidance. The diagnostic performance for pathogen identification by mNGS and sputum culture and for tuberculosis (TB) by mNGS and X-pert MTB/RIF were compared. To evaluate the potential for treatment guidance, we analyzed the treatment regimen of patients with suspected CAP, including imaging changes of lung after empirical antibacterial therapy, intensified regimen, antifungal treatment, and a 1-year follow up for patients with unconfirmed diagnosis and non-improvement imaging after anti-infective treatment and patients with high suspicion of TB or NTM infection who were transferred to the Wuhan Pulmonary Hospital for further diagnosis and even anti-mycobacterium therapy.
RESULTS: Of the 516 BALF samples that were analyzed by both mNGS and sputum culture, the positivity rate of mNGS was significantly higher than that of sputum culture (79.1% vs. 11.4%, P = 0.001). A total of 48 samples from patients with confirmed TB were analyzed by both mNGS and X-pert MTB/RIF, and the sensitivity of mNGS for the diagnosis of active TB was significantly lower than that of X-pert MTB/RIF (64.6% vs. 85.4%, P = 0.031). Of the 106 pathogen-negative cases, 48 were ultimately considered non-infectious diseases, with a negative predictive value of 45.3%. Of the 381 pathogen-positive cases, 311 were eventually diagnosed as CAP, with a positive predictive value of 81.6%. A total of 487 patients were included in the evaluation of the therapeutic effect, and 67.1% improved with initial empirical antibiotic treatment. Of the 163 patients in which bacteria were detected, 77.9% improved with antibacterial therapy; of the 85 patients in which fungi were detected, 12.9% achieved remission after antifungal therapy.
CONCLUSIONS: Overall, mNGS had unique advantages in the detection of suspected CAP pathogens. However, mNGS was not superior to X-pert MTB/RIF for the diagnosis of TB. In addition, mNGS was not necessary as a routine test for all patients admitted with suspected CAP. Furthermore, when fungi are detected by mNGS, antifungal therapy should be cautious.
摘要：
背景：宏基因组下一代测序（mNGS）的出现可能为早期和全面识别社区获得性肺炎（CAP）的病原体提供了有希望的工具。在这项研究中,我们旨在进一步评估mNGS在疑似CAP中的病因诊断价值.
方法：从541例疑似CAP患者中收集555份支气管肺泡灌洗液（BALF）样本，用于mNGS病原体检测。根据感染诊断和治疗指导评估临床价值。比较了mNGS和痰培养对病原体鉴定的诊断性能以及mNGS和X-pertMTB/RIF对结核病（TB）的诊断性能。为了评估治疗指导的潜力，我们分析了疑似CAP患者的治疗方案，包括经验性抗菌治疗后肺部影像学改变，强化治疗方案，抗真菌治疗,对诊断未确诊且在抗感染治疗后影像学检查未改善的患者以及高度怀疑TB或NTM感染的患者转至武汉肺科医院进行进一步诊断甚至抗分枝杆菌治疗的患者进行1年随访。
结果：在通过mNGS和痰培养分析的516个BALF样本中，mNGS阳性率明显高于痰培养(79.1%vs.11.4%,P=0.001)。通过mNGS和X-pertMTB/RIF分析了来自确诊结核病患者的48个样本，mNGS诊断活动性TB的敏感性明显低于X-pertMTB/RIF（64.6%vs.85.4%,P=0.031)。在106例病原体阴性病例中，48人最终被认为是非传染性疾病，阴性预测值为45.3%。在381例病原体阳性病例中，311最终被诊断为CAP，阳性预测值为81.6%。共纳入487例患者的治疗效果评价,和67.1％的改善与最初的经验性抗生素治疗。在检测到细菌的163名患者中，77.9％通过抗菌治疗得到改善；在检测到真菌的85例患者中，12.9%抗真菌治疗后缓解。
结论：总体而言，mNGS在可疑CAP病原体的检测中具有独特的优势。然而,mNGS在诊断TB方面并不优于X-pertMTB/RIF。此外,对于所有疑似CAP患者，不需要将mNGS作为常规检查。此外，当真菌被MNGS检测到时，抗真菌治疗应谨慎。
方法：从541例疑似CAP患者中收集555份支气管肺泡灌洗液（BALF）样本，用于mNGS病原体检测。根据感染诊断和治疗指导评估临床价值。比较了mNGS和痰培养对病原体鉴定的诊断性能以及mNGS和X-pertMTB/RIF对结核病（TB）的诊断性能。为了评估治疗指导的潜力，我们分析了疑似CAP患者的治疗方案，包括经验性抗菌治疗后肺部影像学改变，强化治疗方案，抗真菌治疗,对诊断未确诊且在抗感染治疗后影像学检查未改善的患者以及高度怀疑TB或NTM感染的患者转至武汉肺科医院进行进一步诊断甚至抗分枝杆菌治疗的患者进行1年随访。
结果：在通过mNGS和痰培养分析的516个BALF样本中，mNGS阳性率明显高于痰培养(79.1%vs.11.4%,P=0.001)。通过mNGS和X-pertMTB/RIF分析了来自确诊结核病患者的48个样本，mNGS诊断活动性TB的敏感性明显低于X-pertMTB/RIF（64.6%vs.85.4%,P=0.031)。在106例病原体阴性病例中，48人最终被认为是非传染性疾病，阴性预测值为45.3%。在381例病原体阳性病例中，311最终被诊断为CAP，阳性预测值为81.6%。共纳入487例患者的治疗效果评价,和67.1％的改善与最初的经验性抗生素治疗。在检测到细菌的163名患者中，77.9％通过抗菌治疗得到改善；在检测到真菌的85例患者中，12.9%抗真菌治疗后缓解。
结论：总体而言，mNGS在可疑CAP病原体的检测中具有独特的优势。然而,mNGS在诊断TB方面并不优于X-pertMTB/RIF。此外,对于所有疑似CAP患者，不需要将mNGS作为常规检查。此外，当真菌被MNGS检测到时，抗真菌治疗应谨慎。
