【作者】 孙琳；

【导师】 韩恩吉；

【作者基本信息】 山东大学 ， 内科学， 2006， 博士

【摘要】 研究背景 中枢神经系统感染是神经系统的常见疾病。近年来，由于临床诊断策略的改进、疫苗接种及大量广谱抗生素的应用，细菌性感染的病死率明显下降。然而，随着社会经济的迅速发展，人员流动性明显增大，加之严重的环境污染、交通事故致脑外伤发生率增高等，中枢神经系统细菌感染率呈上升趋势。细菌性脑膜炎仍位居世界感染性疾病病死率的前十位，且因病原菌诊断困难、治疗延误及滥用抗生素等，约25％～50％的细菌性脑膜炎存活者仍遗留肢体活动障碍、失语、癫痫、智力障碍等后遗症。本病最常见的病原菌为脑膜炎奈瑟菌、肺炎链球菌、流感嗜血杆菌B型，病死率分别为10.3％、26.3％及6.0％。近年来结核性脑膜炎亦呈死灰复燃之势。快速、准确地诊断病原菌，早期合理应用抗菌药物迅速控制病情，是降低死亡率、防止并发症的最有效措施。临床病原菌诊断的“金标准”为细菌培养，但由于某些细菌生长困难、培养要求条件太高、培养前已经应用抗生素等原因，细菌培养的阳性率极低，国外报道只有3.1％～8.3％，且培养周期长，一般需24～48h，而结核分枝杆菌则需2～6周。因此，目前临床工作中，大多依据临床表现、脑脊液的细胞学、生化、免疫学检查及血常规等综合指标，推测细菌或其它致病源感染的可能性。由于病原菌诊断方面的限制，从某种程度上，滥用抗生素已经成为临床工作者的无奈之举，不但误诊及漏诊的发生率增高，而且造成医疗资源的极大浪费。 分子生物学理论和技术的迅速发展，尤其是作为生物技术里程碑的多聚酶链反应(polymerase chain reaction，PCR)的问世，为我们在分子水平精确鉴定病原菌打开了一扇窗口。依据某种细菌的致病基因，设计特异引物，通过扩增其特异性片段来对病原菌作出鉴定，目前已经建立了检测结核分枝杆菌、单纯疱疹病毒、更多还原

【Abstract】 IntroductionCentral nervous system bacterial infection is a commom disease . In recent years, because of the improvement of clinical diagnosis , vaccine inoculation and the modern antimicrobial therapy. , the fatality of this disease has been decreased. However, the prevalence of bacterial meningitis is obviously increased because of several factors such as the increased flowability of population , severe environmental pollution and the higher increased traffic accidence . Now bacterial meningitis is still a "top 10" infectious cause of death worldwide, and about 25%~50% of the survivors have neurologic and other sequelae of the disease such as seizure, hemiparesis, aphasia, dementia and so on. The most common pathogenic bacteria are Neisseria meningitides, Streptococcus pneumoniae and Hemophilies influenzae . Cerebral tuberculosis is seem to be rekindled in recent decade. To reduce death or permanent neurological sequelae as much as possible, a fast and correct diagnosis is of the utmost importance. The current "gold standard "for the diagnosis of bacterial meningitis is bacteria culture of cerebrospinal fluid (CSF). However, this approach might have some disadvantages. Some bacteria are very difficult to grow in nutrient medium and the results of culture may only be available after 24 to 48 h . Moreover, this methods sometimes have low sensitivity, especially when antibiotics have been given to the patient prior to lumbar puncture. The positive rate of bacterial culture is only 3.1%. Therefore, at present , the diagnosis of bacterial meningitis is usually based on the clinical presentation of the patient and the findings in CSF including cytology, biochemistry and immunologic test. To some extent, abusing antibiotic has become更多还原