首次复治肺结核患者对治疗方案药品敏感性与治疗转归的相关性分析  

Analysis of the correlation between sensitivity of drugs in the treatment and the outcome of treatment in pulmonary tuberculosis patients retreated for the first time

作　　者：应若嫣 黄晓辰[1] 王洁[1] 刘一典[2] 沙巍[1,2] 杨华[1] YING Ruo-yan;HUANG Xiao-chen;WANG Jie;LIU Yi-dian;SHA Wei;YANG Hua(Shanghai Key Laboratory of Tuberulos,Shanghai Pulmonary Haspital Affiliated to Tongji Universily,Shanghai 200433.China)

机构地区：[1]同济大学附属上海市肺科医院/上海市结核病(肺)重点实验室,200433 [2]同济大学附属上海市肺科医院结核病临床研究中心

出　　处：《中国防痨杂志》2021年第10期1001-1005,共5页Chinese Journal of Antituberculosis

基　　金：“十三五”国家科技重大专项(2018ZX10722302-004)。

摘　　要：目的分析应用超短程治疗方案的首次复治肺结核患者治疗前对方案中药品的单药最低抑菌浓度(MIC)及联合抑菌浓度指数(FICI)对其治疗转归的预测价值。方法搜集2011年7月至2015年12月于同济大学附属上海市肺科医院应用首次复治肺结核超短程治疗方案(Mfx-Pa-Rft-E-Z;为期6个月;Mfx:莫西沙星;Pa:对氨基水杨酸异烟肼;Rft:利福喷丁;E:乙胺丁醇;Z:吡嗪酰胺)并完成治疗疗程的48例首次复治耐药肺结核患者作为研究对象,其中,38例治疗疗程结束痰菌阴转(成功组),10例痰菌未阴转(失败组);成功组广泛耐药(XDR)者18例,耐多药(MDR)者20例;失败组均为XDR。收集研究对象于治疗前保存的痰标本培养分离结核分枝杆菌(MTB)菌株,采用三维棋盘法对Mfx、Pa、Rft及Mfx-Pa、Pa-Rft、Mfx-Pa-Rft进行体外药物敏感性试验(简称"药敏试验"),分析MIC和FICI与患者治疗转归的相关性。结果 Mfx、Pa和Rft单药MIC值[中位数(四分位数)]成功组分别为0.50(0.06,1.00)、8.0(3.5,16.0)、32.0(4.0,64.0)mg/L;失败组分别为1.00(0.50,1.00)、16.0(3.5,28.0)、48.0(24.5,64.0)mg/L。成功组Mfx的MIC值明显低于失败组,差异有统计学意义(Z=-2.251,P=0.026)。Mfx-Pa和Pa-Rft联合药敏试验结果显示,成功组协同率分别为2.6%(1/38)和44.7%(17/38),失败组的协同率分别为1/10和6/10,均无拮抗产生,两组间差异无统计学意义(Fisher精确概率法,P值分别为0.377和0.487)。Mfx-Pa-Rft联合药敏试验结果显示,成功组协同率为26.3%(10/38),失败组协同率为1/10;成功组拮抗率为13.2%(5/38),失败组拮抗率为3/10,两组间差异无统计学意义(χ^(2)=2.221,P=0.136)。针对XDR患者的Mfx-Pa-Rft联合药敏试验结果显示,成功组协同率为38.9%(7/18),高于失败组(1/10);拮抗率为5.6%(1/18),小于失败组(3/10),差异有统计学意义(χ^(2)=4.480,P=0.034)。成功组Mfx-Pa联合药敏试验的FICI值[中位数(四分位数)]为1.50(1.00,2.00),失败组为1.75(1.05,2.02);成功Objective To analyze the predictive value of single-drug minimum inhibitory concentration(MIC and fractional inhibitory concentration index(FICI)to the outcome of treatment in pulmonary tuberculosis patients firstly retreated with ultra-short course treatment. Methods Forty-eight drug-resistant tuberculosis patients firstly retreated with the ultra-short course treatment for pulmonary(Mfx-Pa-Rft-E-Z;6 months;Mfx:moxifloxacin;Pa:isoniazid para amino salicylic acid;Rft:rifapentine;E:ethambutol;Z:pyazinamide)from Shanghai Pulmonary Hospital Affiliated to Tongji University were selected.All the patients completed the treatment and were divided into successful group(n=38,sputum was negative after treatment)and failure group(n=10,sputum was not negative after treatment).In the successful group,18 patients were extensive-drug resistance(XDR)and 20 patients were multidrug-drug resistance(MDR).Patients in failure groups were all XDR.Strains were isolated from sputum specimens preserved before treatment.In vitro drug sensitivity test was performed on Mfx,Pa,Rft and Mfx-Pa,Pa-Rft,Mfx-Pa-Rft by three-dimensional checkboard method.The correlation between MIC and FICI and prognosis was analyzed. Results MIC values(median(quartile))of Mfx,Pa and Rft were0.50(0.06,1.00),8.0(3.5,16.0)and 32.0(4.0,64.0)mg/L,respectively,in the successful group,and 1.00(0.50,1.00),16.0(3.5,28.0)and 48.0(24.5,64.0)mg/L,respectively,in the failure group.The MIC value of Mfx in the successful group was significantly lower than that in the failure group(Z=-2.251,P=0.026).The results of the combined drug sensitivity test of Mfx-Pa and Pa-Rft showed that the synergistic rates of the successful group were 2.6%(1/38)and 44.7%(17/38),and of the failure group were 1/10 and 6/10,respectively.No antagonism was found,and the difference between the two groups was not statistically significant(Fisher’s exact probability method,Pvalues were 0.377 and 0.487,respectively).The results of Mfx-Pa-Rft combined drug sensitivity test showed that the synergistic rates we

关 键 词：结核 肺 再治疗 抗药性 多药 微生物敏感性试验 结果评价(卫生保健) 

分 类 号：R52[医药卫生—内科学]