两性霉素B快速加量治疗隐球菌性脑膜炎疗效和安全性分析  

Analysis of efficacy and safety of rapid add on amphotericin B for the treatment of HIV-negative cryptococcal meningitis

作　　者：杨露 刘佳[1] 江滢[1] 王翼洁 徐晓峰[1] 甘周庆 陈灼林 彭福华[1] YANG Lu;LIU Jia;JIANG Ying;WANG Yijie;XU Xiaofeng;GAN Zhouqing;CHEN Zhuolin;PENG Fuhua(the Third Affiliated hospital of Sun Yet-San University,Guangzhou 510000,China)

机构地区：[1]中山大学附属第三医院神经内科,广州510000

出　　处：《中国神经精神疾病杂志》2021年第6期348-354,共7页Chinese Journal of Nervous and Mental Diseases

基　　金：国家自然科学基金面上项目(编号:82071265);广东省科技计划项目(编号:2017B020230003)。

摘　　要：目的探讨两性霉素B普通针剂快速加量方法治疗人类免疫缺陷病毒阴性隐球菌性脑膜炎的疗效及安全性。方法回顾性分析我院2014年至2019年间41例确诊为隐球菌性脑膜炎的病例,按照两性霉素B加量速度的不同将病例分为快速加量组与常规加量组:若两性霉素B增量>5 mg/d或加量至0.5 mg/kg剂量所需时间<7 d,则纳入快速加量组;若增量<5 mg/d或加量至0.5 mg/kg剂量所需时间≥7 d,则纳入常规加量组。通过对比两组患者的隐球菌涂片转阴时间、住院时间、出院时及10周后返院复查时的治疗有效率评估其疗效差异,通过对比两组之间血电解质紊乱、肝肾功能损伤的发生率来评估两组之间的安全性差异。结果快速加量组与常规加量组患者隐球菌涂片转阴时间分别为12.00(5.00,22.00)d vs.41.00(24.75,91.50)d,住院时间分别为25.00(20.20,44.25)d vs.40.00(34.00,53.00)d,差异有统计学意义(P<0.05);两组出院时治疗有效率、电解质紊乱、肝功能不全、肾功能不全发生率分别为86.36%vs.63.16%、45.45%vs.31.58%、36.36%vs.15.79%、40.90%vs.42.11%,10周后返院复查时分别为81.82%vs.78.95%、16.67%vs.25.00%、11.11%vs.6.25%、11.11%vs.37.50%,两组之间无统计学差异(P>0.05)。结论两性霉素B普通针剂快速加量治疗隐球菌性脑膜炎可使患者脑脊液隐球菌清除速度加快、住院时间缩短,其不良反应发生率与传统加量法相似,临床可推广使用。Objective To evaluate the efficacy and safety of rapid add on Amphotericin B(AmB)for the treatment of patients with HIV-negative Cryptococcal meningitis.Method Forty-one cases were recruited from 2014 to 2019 from the Third Affiliated hospital of Sun Yet-San University.Patients were further divided into two groups:rapid add on and routing add on groups.In the rapid add on group,the patients received rapid add on AmB-the increment was greater than 5mg per day or the total days needed for escalating to the target dose(0.5mg/kg)were fewer than 7 days.While in the routing add on group,the increment was fewer than 5mg per day or the total days was more than 7 days or the highest dose was fewer than 0.5mg/kg.The efficacy was evaluated by measuring negative conversion time of cerebrospinal fluid(CSF)cryptococcal organisms count as evidenced by India ink stain,hospital stay and the effective rate at discharge or at reexamination 10 weeks after discharge.The safety was evaluated by measuring incidence of electrolyte disturbances and liver and kidney function damage.SPSS25.0 was used for statistical analysis.Result The negative conversion time of cryptococcal smear was 12.00(5.00,22.00)d in rapid add on group vs.41.00(24.75,91.50)d in routing add on group and the length of hospital stay was 25.00(20.20,44.25)d in rapid add on group vs.40.00(34.00,53.00)d in routing add on group respectively(P<0.05).The rates of effective rate,electrolyte disorder,liver insufficiency and renal insufficiency were 86.36%vs.63.16%,45.45%vs.31.58%,36.36%vs.15.79%,40.90%vs.42.11%at discharge,and 81.82%vs.78.95%,16.67%vs.25.00%,11.11%vs.6.25%,11.11%vs.37.50%at return to hospital after 10 weeks,respectively(P>0.05).Conclusion Rapid add on AmB in the treatment of cryptococcal meningitis can accelerate the clearance rate of Cryptococcus in the CSF and shorten the hospital stay but with similar side effects with routing add on therapy which is worth promoting in clinical application.

关 键 词：隐球菌性脑膜炎 两性霉素B 快速加量 疗效 安全性 

分 类 号：R742.6[医药卫生—神经病学与精神病学]