摘要：

目的: 探讨集束化治疗方案对于重度颅内感染的疗效。方法: 共纳入2020年7月至2023年6月深圳大学总医院和广东省深圳市第二人民医院收治的43例重度颅内感染患者，采取集束化治疗方案，先予以广谱抗生素；多途径引流并获取脑脊液行常规和生化检测、微生物培养及第二代测序（NGS）；完善头部和胸部CT和（或）MRI平扫和增强扫描；待脑脊液NGS测序结果回报后精准调整抗生素治疗方案；序贯引流脑脊液；严重脑室内感染患者予脑室镜（软式内镜）冲洗和脑室造瘘；定期复查行脑脊液和血液感染指标测定和微生物培养，待各项指标正常1周后调整抗生素或停药；根据临床表现、实验室和影像学检查结果综合判断疗效。结果: 16例予广谱抗生素美罗培南+ 万古霉素抗感染治疗；脑脊液检查，微生物（细菌、真菌、病毒）培养阳性12例（27.91%），NGS测序阳性35例（81.40%），经NGS测序明确病原体后，15例调整为敏感抗生素，12例症状明显改善、3例无明显改善；27例（62.79%）行外科治疗，包括脓肿穿刺引流术7例（16.28%）、Ommaya囊植入术6例（13.95%）、脑室外引流术11例（25.58%，其中8例行脑室镜冲洗和脑室造瘘）、腰大池引流术3例（6.98%）；住院时间为30（19，57）d，37例（86.05%）治愈出院、6例（13.95%）死亡。结论: 重度颅内感染患者经集束化治疗后治愈率显著提高，早期启动集束化治疗方案可明显改善患者预后，值得临床推广应用。

关键词: 中枢神经系统感染, 集束化治疗（非MeSH词）, 脑脊髓液, 序列分析, DNA, 抗菌药

Abstract:

Objective: To investigate the efficacy of cluster therapy in the treatment of severe intracranial infection. Methods: The clinical data of 43 patients with severe intracranial infection in Shenzhen University General Hospital and Shenzhen Second People's Hospital from July 2020 to June 2023 were retrospectively analyzed. Patients with intracranial infection were treated with cluster therapy: systemic broad-spectrum antibiotics were used at first; cerebrospinal fluid was obtained by multiple drainage routes for routine and biochemical testing, and then cultured and undertook next-generation sequencing (NGS); head/chest CT and brain MRI plain and enhanced scan were performed; after the NGS results were reported, precisely adjust the drug treatment according to the infection pathogen; sequentially use different drainage protocols of infected cerebrospinal fluid. Patients with severe intraventricular inflammation were treated with ventriculoscope (flexible endoscope) irrigation and fistula; cerebrospinal fluid, microbial culture and whole blood test for infection indicators were regularly extracted for laboratory test, and the type and dosage of antibiotics were adjusted one week after the indicators returned to normal, and the treatment effect of patients was judged comprehensively according to blood, cerebrospinal fluid, imaging results and clinical signs of infection. Results: Sixteen patients were administered a broad-spectrum antibiotic regimen consisting of meropenem and vancomycin.Cerebrospinal fluid analysis revealed that 12 cases (27.91%) were culture-positive for microbial organisms (bacteria, fungi, viruses), while 35 cases (81.40%) yielded positive results in NGS. Upon identification of the pathogen via NGS, 15 cases were switched to targeted, sensitive antibiotics, with 12 cases exhibiting notable improvements in symptoms, and 3 cases demonstrating no significant changes. A total of 27 patients (62.79%) underwent surgical intervention, including 7 patients (16.28%) who underwent abscess puncture drainage, 6 patients (13.95%) who received Ommaya sac implantation, 11 patients (25.58%) who underwent external ventricular drainage (8 of whom also underwent ventriculoscopic irrigation and ventriculostomy), and 3 patients (6.98%) who were treated with lumbocisterna drainage. The length of hospitalization was 30 (19, 57) d. The 37 cases (86.05%) were successfully cured, while 6 cases (13.95%) died. Conclusions: The cure rate of patients with severe intracranial infection was significantly improved after cluster therapy, and early initiation of cluster therapy can significantly improve the prognosis of patients, which is worthy of clinical application.

Key words: Central nervous system infections, Cluster therapy (not in MeSH), Cerebrospinal fluid, Sequence analysis, DNA, Anti-bacterial agents