含环丝氨酸方案治疗耐多药肺结核患者发生不良反应的临床分析  

Analysis on the adverse events among multidrug-resistant pulmonary tuberculosis patients receiving cycloserine-containing regimen

作　　者：王敬[1] 荆玮[1] 陈维[1] 郭茹[1] 韩喜琴[1] 吴琍敏[2] 杨光旭 杨坤云 陈聪 蒋凛 蔡春葵 窦志 刁丽娟 潘洪秋 王建云 杜斐斐 王黎霞[13] 李仁忠[13] 初乃惠[1] WANG Jing;JING Wei;CHEN Wei;GUO Ru;HAN Xi-qin;WU li-min;YANG Guang-xu;YANG Kun-yun;CHEN Cong;JIANG Lin;CAI Chun-kui;DOU Zhi;DIAO Li-juan;PAN Hong-qiu;WANG Jian-yun;DU Fei-fei;WANG Li-xia;LI Ren-zhong;CHU Nai-hui(Department of Tuberculosis,Beijing Chest Hospital,Capital Medical University,Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China)

机构地区：[1]首都医科大学附属 北京胸科医院北京市结核病胸部肿瘤研究所结核一科,101149 [2]杭州市疾病预防控制中心结核病预防控制所 [3]长春市传染病医院结核病防治所 [4]湖南省胸科医院耐药科 [5]武汉市肺科医院耐多药项目办 [6]赣州市第五人民医院内科一区 [7]大连市结核病医院耐药病房 [8]齐齐哈尔市结核病防治所结核科 [9]南阳市结核病防治所结核内科 [10]镇江市第三人民医院结核病科 [11]兰州市肺科医院感染科 [12]宁夏回族自治区第四人民医院呼吸科 [13]中国疾病预防控制中心结核病预防控制中心

出　　处：《中国防痨杂志》2018年第8期810-814,共5页Chinese Journal of Antituberculosis

摘　　要：目的 分析含环丝氨酸（Cs）化疗方案治疗耐多药肺结核患者发生药物不良反应的情况。方法 选取2013年1月至2016年6月全国11家单位纳入全球基金第五轮耐多药结核病防治项目、符合选例标准的耐多药肺结核患者作为研究对象,共计623例。所有患者均采用标准化治疗方案,即：6PZA-Am（Cm）-Lfx（Mfx）-Pto-Cs/18PZA-Lfx（Mfx）-Pto-Cs;替代方案：PAS替代Pto,Cm替代Am,Mfx替代Lfx（PZA：吡嗪酰胺;Am：阿米卡星;Cm：卷曲霉素;Lfx：左氧氟沙星;Mfx：莫西沙星;Pto：丙硫异烟胺;Cs：环丝氨酸;PAS：对氨基水杨酸钠）。收集患者在治疗过程中的药物不良反应发生情况,分析药物不良反应的临床特征、严重程度、发生时间、持续时间、处理方法及预后,并判定其与药物之间的相关性。结果 623例研究对象中有316例（50.7%）发生至少一种药物不良反应,36例（5.8%）患者由于药物不良反应停服药物或者更改治疗方案。最常见的药物不良反应为高尿酸血症（22.8%,142/623）和肝功能异常（18.8%,117/623）;出现与Cs很可能相关的中枢神经系统或精神症状者有27例（4.3%）,发生时间的中位数（四分位数）[M（Q1,Q3）]为3（2,6）个月,对患者进行停用Cs或心理辅导等处理后,症状消失。结论 应用含Cs的标准化疗方案进行治疗的耐多药肺结核患者中,发生中枢神经系统或精神症状与Cs有关,在对患者使用含Cs方案治疗期间需密切监测其中枢神经系统或精神系统症状。Objective To analyze the adverse events in multidrug-resistant pulmonary tuberculosis patients treated with cycloserine-containing chemotherapy regimen.Methods A total of 623 multidrug-resistant pulmonary tuberculosis patients who were eligible for inclusion in the Global Fund＇s fifth round of multidrug-resistance control program during January 2013 to June 2016 from 11 hospitals in China were selected. All patients used a standardized treatment regimen： 6PZA-Am（Cm）-Lfx（Mfx）-Pto-Cs/18PZA-Lfx（Mfx）-Pto-Cs; alternatives： PAS instead of Pto, Cm instead of Am, Mfx replacement Lfx （PZA： pyrazinamide, Am： amikacin, Cm： capreomycin, Lfx： levofloxacin, Mfx： moxifloxacin, Pto： prothionamide, Cs： cycloserine, PAS： p-aminosalicylide sodium）. The adverse events during treatment were collected, their clinical characteristics, severity, occurring time, duration, treatment method and prognosis were analyzed, and the correlation between the drugs and adverse events were determined.Results Of the 623 multidrug-resistant pulmonary tuberculosis patients treated with cycloserine-containing regimen, 316 （50.7%） patients had at least one adverse event, and 36 （5.8%） patients discontinued the treatment or changed the treatment regimen due to adverse reactions. The most common adverse reactions were hyperuricemia （22.8%, 142/623） and abnormal liver function （18.8%, 117/623）. Twenty-seven （4.3%, 27/623） patients developed central nervous system or psychiatric symptoms that were likely to be associated with cycloserine, and the median （interquartile range） time of occurrence was 3 （2, 6） months. After drug discontinuance or psychological counseling, the symptoms disappeared.Conclusion In multidrug-resistant pulmonary tuberculosis patients who received cycloserine-containing regimen, the occurrence of nervous system or psychiatric symptoms was mainly related to cycloserine. Patients need to be closely monitored for these symptoms during treatment that includes cycloserine.

关 键 词：环丝氨酸 结核 抗多种药物性 药物毒性 药物评价 

分 类 号：R969.3[医药卫生—药理学]