Wang Lili, Guo Wenzheng, Shen Hui, Guo Jian, Wen Donghua, Yu Yuetian, Wu Wenjuan
Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Critical Care Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Mol Biosci. 2021 May 28;8:659390. doi: 10.3389/fmolb.2021.659390. eCollection 2021.
Sepsis is a common life-threatening disease in the intensive care unit (ICU) that is usually treated empirically without pathogen identification. As a non-invasive and high-throughput technology, plasma microbial cell-free DNA (mcfDNA) sequencing can detect unknown pathogens independent of previous clinical or laboratory information. In this study, a total of 199 cases suspected of bloodstream infection (BSI) from January 2020 to June 2020 were collected, and potential pathogens were detected by simultaneous blood culture and plasma mcfDNA sequencing. Other clinical microbiological assays were performed within 7 days of plasma mcfDNA sequencing, including smear, culture of samples taken from relevant infected sites, and β-D-glucan/galactomannan (BDG/GM) tests, among others. The diagnoses were classified as sepsis [94 (47.2%)], non-sepsis [87 (43.7%)], and non-infectious disease [18 (9.0%)]. The sensitivity and specificity of plasma mcfDNA sequencing for diagnosing sepsis were 68.1 and 63.2%, respectively, which were significantly better than those of blood culture, especially for the common bacteria that cause hospital-acquired infection, namely, ( < 0.01) and ( < 0.01), and DNA viruses (plasma mcfDNA sequencing only, < 0.01). However, there was no significant difference in the rate of positivity between plasma mcfDNA sequencing and blood culture for antibiotic-non-exposed cases (43.6 vs. 30.9%, = 0.17). In the non-sepsis group, 44.8% of cases (13/29) detected only by plasma mcfDNA sequencing showed infections in other parts of the body, such as lower respiratory infection (LRI), intra-abdominal infection (IAI) and central nervous system infection (CNSI). For some common pathogens (not including anaerobes), turnaround time (TAT) 3 (TAT from the initiation of blood sample processing by nucleic acid extraction to the completion of sequencing analysis) was longer than TAT1 (TAT from blood culture bottles in Virtuo to off Virtuo). With disease progression, significant dynamic changes in microbial species were clearly detected by plasma mcfDNA sequencing.
脓毒症是重症监护病房（ICU）中一种常见的危及生命的疾病，通常在未明确病原体的情况下进行经验性治疗。作为一种非侵入性的高通量技术，血浆微生物游离DNA（mcfDNA）测序能够独立于先前的临床或实验室信息检测未知病原体。在本研究中，收集了2020年1月至2020年6月期间共199例疑似血流感染（BSI）的病例，并通过同时进行血培养和血浆mcfDNA测序来检测潜在病原体。在血浆mcfDNA测序后的7天内进行了其他临床微生物学检测，包括涂片、从相关感染部位采集样本进行培养以及β-D-葡聚糖/半乳甘露聚糖（BDG/GM）检测等。诊断结果分为脓毒症[94例（47.2%）]、非脓毒症[87例（43.7%）]和非感染性疾病[18例（9.0%）]。血浆mcfDNA测序诊断脓毒症的敏感性和特异性分别为68.1%和63.2%，显著优于血培养，尤其是对于引起医院获得性感染的常见细菌，即（<0.01）和（<0.01），以及DNA病毒（仅血浆mcfDNA测序，<0.01）。然而，对于未使用抗生素的病例，血浆mcfDNA测序和血培养的阳性率没有显著差异（43.6%对30.9%，=0.17）。在非脓毒症组中，仅通过血浆mcfDNA测序检测到的病例中有44.8%（13/29）在身体其他部位出现感染，如下呼吸道感染（LRI）、腹腔内感染（IAI）和中枢神经系统感染（CNSI）。对于一些常见病原体（不包括厌氧菌），周转时间（TAT）3（从通过核酸提取开始处理血样到完成测序分析的TAT）长于TAT1（从Virtuo中的血培养瓶到移出Virtuo的TAT）。随着疾病进展，通过血浆mcfDNA测序可清晰检测到微生物种类的显著动态变化。
