一例格特隐球菌感染引起脑膜脑炎患者的临床表现与实验室鉴定分析

Clinical presentation and laboratory identification analysis for a case of crytococcal meningoencephalitis caused by Cryptococcus gattii

目的探讨格特隐球菌引起脑膜脑炎的临床及病原学特点,为临床和实验室认识及诊疗该类疾病提供帮助。方法分析患者的临床资料、实验室辅助检查、诊疗经过和实验室对病原菌的分离鉴定、药敏试验及18S rRNA序列测定并复习相关文献。结果该患者有慢性肝炎的消耗性、免疫力低下病史,临床表现为头痛、发热和呕吐等,脑部影像学显示病变侵及脑膜和脑实质,一度发生脑疝,病情凶险。实验室检测血常规显示白细胞、中性粒细胞及CRP升高;脑脊液压力明显升高,脑脊液细胞总数、白细胞数、单核细胞及蛋白升高,葡萄糖和氯化物降低,墨汁染色阳性;脑脊液真菌培养在显色培养基上生长为白色菌落,在豆氨酸-甘氨酸-溴麝香草酚蓝(CGB)培养基生长使其变蓝色;分离菌经Vitek-2 Compact鉴定为新型隐球菌(99%),最终经18S rRNA测序和系统发育分析确定为格特隐球菌(相似度>99.0%)。药敏试验结果显示,该菌株对5-氟尿嘧啶、两性霉素B、氟康唑、伊曲康唑和伏立康唑均敏感。临床应用两性霉素B联合氟康唑和5-氟尿嘧啶治疗后患者症状及体征好转,回当地继续治疗。结论 CGB培养基可作为格特隐球菌的初筛培养基,分子学方法较自动化仪器鉴定格特隐球菌更准确可靠;治疗应以两性霉素B和5-氟尿嘧啶为主的联合治疗,早诊断、早治疗、足量和足疗程是治疗隐球菌病的关键。

Objective To investigate the charicteristics of clinic and pathogen of crytococcal meningoencephalitis caused by Cryptococcus gattii and to provide assistance for clinical diagnosis and therapy. Methods The clinical data, laboratory examination, diagnosis and treatment were analyzed, respectively, and the isolation and identifcation of pathogenic fungus, antimicrobial susceptibility testing and 18S rRNA sequence were determined to the isolate. Results The patient had a history of long-term chronic hepatitis and immunodeficiency. Clinical manifestations were strenuous headache, high fever and vomiting. Brain imaging showed that parenchymal was damaged. The detection results of cerebrospinal fuid showed that CSF pressure, the white blood cell count, and protein increased signifcantly, but the glucose and chloride reduced. The ink staining result of CSF was positive. The isolate of CSF in Chromogenic medium was white colonies and Canavanine-glycine-bromthymol blue （CGB） medium showed blue. The isolate was identified as cryptococcus neoformans by Vitek-2 Compact, which was identified as Cryptococcus gattii by 18S rRNA sequencing （similarity 〉 99%） and phylogenetic analysis. Drug susceptibility results showed that Cryptococcus gattii was sensitive tothe 5-fluorouracil, amphotericin B, fluconazole, itraconazole andvoriconazole. Patients symptoms and signs improved after combined application of fuconazole, amphotericin B and 5-fluorouracil. Conclusions Molecular method for identification of Cryptococcus gattii was rapid and accurate. Early pathogenic diagnosis, early combined treatment with amphotericin B and 5-fuorouracil,suffcient and full course of treatment are the key for treatment of crytococcal meningoencephalitis.