【作者】 顾菊林；

【导师】 廖万清； 温海；

【作者基本信息】 第二军医大学 ， 皮肤病学与性病学， 2002， 博士

【摘要】 本文旨在发展新生隐球菌性脑膜炎（隐脑）疗效监测指标和确立合适的治疗方案。研究工作包括：1、应用NCCLS M27-A微量稀释法检测了19株新生隐球菌临床分离株对三种抗真菌药物的敏感性，并与各自临床疗效进行比较。结果参试菌株对AmB的MIC值范围在0.5～2(g/ml，对5-FC的MIC值范围在0.25～8(g/ml，对FCA的MIC值范围在2～32(g/ml，其中AmB的MIC范围最为狭窄，现有资料尚不能确定MIC值与临床效果间的相关性。2、建立了流式细胞仪法快速检测新生隐球菌药物敏感性，与微量稀释法结果相比符合率为87.5%，实验时间由72小时缩短为4～5小时。3、电镜观察、动物接种和菌体直接染色方法鉴定脑脊液菌体活性，作为隐脑临床疗效监测的重要指标。4、通过对隐脑患者与正常对照组外周血免疫指标进行分析，发现隐脑患者外周血CD4+细胞及CD4+/CD8+均显著下降。5、对35例隐脑回顾分析表明采用分期综合治疗方案治疗隐脑，明显优于其他治疗方案；AmB鞘内注射应成为常规治疗，在静滴AmB出现副作用时仍可继续使用；脑脊液真菌培养可作为初期治疗结束的指标，脑脊液隐球菌菌体计数作为疗效监测的主要指标是合适的；7例经治疗痊愈的儿童隐脑中4例出现严重的后遗症，及时有效地进行抗真菌治疗、必要时应用外科手段降颅压是减少后遗症的关键。更多还原

【Abstract】 The aim of this paper is to develop new parameters for evaluating clinical therapeutic efficacy and design reasonable strategy for the treatment of cryptococcal meningitis. The work included: (1) The susceptibilities of 19 clinical cryptococcus neoformans isolates to amphotericin B, 5-flucytosine and fluconazole were determined by NCCLS M27-A broth microdilution method. The correlation of MICs and clinical outcome was calculated. Amphotericin B MICs ranged from 0.5 to 2(g/ml, 5-flucytosine MICs ranged from 0.25 to 8(g/ml, while fluconazole MICs ranged from 2 to 32(g/ml. The M27-A-derived MICs did not correlate with clinical outcome. (2) A rapid flow cytometric assay for in vitro antifungal drug susceptibility testing was developed. Good agreement was shown between flow cytometric and broth macrodilution MICs. Compared with the M27-A macrodilution procedure, this assay was more rapid (4-5h versus 72h). (3) Using electron microscope examination, animal inoculation and neutral red staining, a method for evaluating the viability of cryptococcus in cerebrospinal fluid was developed. (4) Analysis of peripheral blood immune parameters showed patients with cryptococcal meningitis had lower CD4 counts and CD4/CD8 ratios than that in health volunteers. (5) By comparing the efficacy of three different antifungal regimens in the treatment of <WP=7>cryptococcal meningitis, we suggested that the two-step combination therapeutic regimen be well suited to the treatment of cryptococcal meningitis. Intrathecally administered amphotericin B should be recommended, especially when serious toxicity emerged because of systemic administration. Our study also demonstrated that a negative CSF culture for cryptococci as an endpoint for initial treatment was feasible, while CSF cryptococcal count as the most important parameter evaluating clinical outcome was reasonable. Among 7 cases of Cryptococcal meningitis in children, 4 of them had severe sequelae. Management of impending complication combined medical and surgical treatment modalities.更多还原