摘要：

目的: 探讨脑脊液宏基因组学第二代测序（mNGS）在颅内感染诊断与治疗中的应用价值。方法: 纳入2020年1月至2022年12月广东省深圳市第二人民医院收治的117例颅内感染患者，均于启动经验性广谱抗生素治疗前收集脑脊液行微生物培养（常规培养组，58例）和（或）mNGS测序（mNGS组，59例），并根据结果回报调整抗生素治疗方案，对比两种检测方法的病原体检出率和结果回报时间、抗生素强度分级，以及重症监护病房（ICU）住院时间、总住院时间和病死率。结果: 本组117例患者经脑脊液微生物培养和（或）mNGS测序共检出65种病原体，尤以病毒占比最高，为49.23%（32/65），其次依次为革兰阴性菌（24.62%，16/65）、革兰阳性菌（18.46%，12/65）和真菌（7.69%，5/65）。脑脊液mNGS测序的病原体检出率高于（χ² = 22.781，P = 0.000）、结果回报早于（t = - 32.588，P = 0.000）微生物培养；根据结果回报，mNGS组有20例（33.90%）调整抗生素治疗方案，抗生素应用强度降级5例、升级15例，常规培养组有30例（51.72%）调整抗生素治疗方案，抗生素应用强度降级17例、升级13例，组间差异无统计学意义（Z = - 1.917，P = 0.055）；两组ICU住院时间（Z = - 0.716，P = 0.474）、总住院时间（Z = - 0.933，P = 0.351）和病死率（Fisher确切概率法：P = 0.496）差异亦无统计学意义。结论: 脑脊液mNGS测序可以有效提高颅内感染病原体检出率，尽可能减少广谱抗生素应用时间、降低抗生素总体应用强度，有助于临床准确诊断与精确治疗。

关键词: 中枢神经系统感染, 脑脊髓液, 序列分析, DNA, 细菌学技术, 抗菌药

Abstract:

Objective: To investigate the effect of cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) in diagnosis and treatment of intracranial infection. Methods: A retrospective analysis of 117 patients with intracranial infection were admitted to Shenzhen Second People's Hospital from January 2020 to December 2022. Before initiating empirical broad-spectrum antibiotic treatment, CSF samples were collected for microbial culture (conventional culture group, n = 58) and/or mNGS (mNGS group, n = 59). The results were used to adjust the antibiotic treatment plan, and the study compared the pathogen detection rates and result reporting times of the two testing methods, as well as the antibiotic intensity grading, the intensive care unit (ICU) stay, total hospital stay, and mortality rate. Results: A total of 65 pathogens were detected from the CSF samples of all the patients through microbial culture and/or mNGS, with viruses being the most prevalent, accounting for 49.23% (32/65), followed by Gram-negative bacteria (24.62%, 16/65), Gram-positive bacteria (18.46%, 12/65) and fungi (7.69%, 5/65). The pathogen detection rate of CSF mNGS was higher than that of CSF microbial culture (χ² = 22.781, P = 0.000), and the results were reported earlier (t =-32.588, P = 0.000). Based on the results, 20 cases (33.90%) in the mNGS group adjusted antibiotic treatment plan, with 5 cases downgrading and 15 cases upgrading the intensity of antibiotic application. In the conventional culture group, 30 cases (51.72%) adjusted their antibiotic treatment plan, with 17 cases downgrading and 13 cases upgrading the intensity of antibiotic application. There was no significant difference between the 2 groups (Z =-1.917, P = 0.055). And there was no statistically significant difference in ICU stay (Z =-0.716, P = 0.474), total hospital stay (Z =-0.933, P = 0.351) and mortality rate (Fisher's exact probability: P = 0.496) between the 2 groups. Conclusions: The application of mNGS can effectively improve the detection rate of intracranial infection pathogens, which may shorten the duration of antibiotic use and reduce the intensity of broad-spectrum antibiotics, so as to help clinical effective judgment and treatment decision.

Key words: Central nervous system infections, Cerebrospinal fluid, Sequence analysis, DNA, Bacteriological techniques, Anti-bacterial agents