摘要：

目的 探讨基于宏基因组的第二代测序技术（mNGS）在神经外科手术后并发颅内感染诊断中的应用价值。方法 前瞻性纳入2019年1-10月共15例神经外科手术后拟诊颅内感染患者，2周后由3位神经外科专家共同判断是否确诊颅内感染。腰椎穿刺留取脑脊液标本，分别行常规、生化、细菌涂片和细菌培养以及mNGS测序。结果 共8例患者临床确诊术后颅内感染，其中4例脑脊液mNGS测序（序列数分别为212、329、1601和5371）和细菌培养（鲍曼不动杆菌2例、皮特不动杆菌1例、产气肠杆菌1例）均呈阳性；4例经随访临床确诊术后颅内感染，但脑脊液mNGS测序和细菌培养均呈阴性。7例临床诊断为无菌性脑膜炎，其中3例脑脊液mNGS测序序列数< 100；1例脑室外引流管管头细菌培养为表皮葡萄球菌，但脑脊液mGNS测序呈阴性，随访后确认为污染所致。脑脊液mNGS测序诊断术后颅内感染的灵敏度为4/8、特异度为7/7，准确率为11/15。结论 初步证实mNGS测序诊断神经外科手术后并发颅内感染有一定价值，可以作为传统检测方法的有效补充，但mNGS测序结果须结合临床实际情况合理判读。

关键词: 宏基因组, 基因检测, 神经外科手术, 手术后并发症, 中枢神经系统感染

Abstract:

Objective To investigate the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of intracranial infection after neurosurgery. Methods Fifteen patients suspected of intracranial infection after neurosurgery were prospectively enrolled in Department of Neurosurgery of Xuanwu Hospital of Capital Medical University from January to October, 2019. Two weeks later, three neurosurgeons analyzed and judged whether it was clinical intracranial infection. The cerebrospinal fluild (CSF) routine, biochemical, bacterial smear and culture were recorded. The same CSF sample was sent for mNGS. All cases were followed up for 3 months, and the final diagnosis and treatment outcome were recorded. Results Eight cases were clinically diagnosed as intracranial infection. Among them positive for bacterial culture and mNGS, 3 cases were negative for both, one case was positive for bacterial smear in CSF at the early stage, but negative for culture and mNGS. Diagnosis of intracranial infection were excluded in 7 cases clinically. All the 7 cases were negative for bacterial culture and mNGS, one case was positive for bacterial culture of Staphylococcus epidermidis with head of ventricular drainage tube, and negative for bacterial culture and mNGS in CSF. The bed was judged to be contaminated by the tube head specimen. The number of detection sequence of pathogenic bacteria genes in the 4 cases with positive mNGS was 212, 329, 1601 and 5371, which was accompanied by the decrease of glucose and the increase of leukocyte in CSF. The number of gene sequences of non-infectious background bacteria was less than 100. The sensitivity and specificity of mNGS sequencing in the diagnosis of postoperative intracranial infection were 4/8 and 7/7, and the accuracy was 11/15. Conclusions The clinical value of mNGS in the diagnosis and treatment of intracranial infection after neurosurgery is preliminarily verified. Based on the traditional detection method, mNGS in CSF can be used as a supplement, but the detection of mNGS must be interpreted reasonably according to the clinical situation.

Key words: Metagenome, Genetic testing, Neurosurgical procedures, Postoperative complications, Central nervous system infections