强化期含利奈唑胺方案治疗耐多药结核病的临床观察

Clinical observation of intensive phase with linezolid in treatment of multidrug resistant tuberculosis

目的探索强化期含利奈唑胺(linezolid,Lzd)方案治疗耐多药肺结核病(multidrug-resistant tuberculosis,MDR-TB)的疗效、对免疫学的影响及安全性。方法选择2017年3月~2019年10月之间我院收治的92例耐多药肺结核病患者,采用随机数字表法分为观察组和对照组各46,对照组采用标准化疗方案治疗,观察组在对照组治疗基础上加用Lzd,比较两组患者治疗3个月、6个月末时的痰菌转阴率、痰培养阴转率;6个月末时的病灶显著吸收率、临床症状改善率、空洞缩小闭合率;分析两组治疗前后T淋巴细胞亚群的差异及药物不良反应的发生情况,以P<0.05为差异有统计学意义。结果观察组患者在治疗3、6个月末时痰菌转阴率,痰培养转阴率分别为76.09%(35/46)、91.30%(42/46)、73.93%(34/46)、91.30%(42/46),均高于对照组的54.35%(25/46)、73.91%(34/46)、52.17%(24/46)、71.74%(33/46),差异均有统计学意义(χ^(2)值分别为4.792、4.842、4.665、5.844,P值均<0.05);治疗6个月末时观察组患者病灶显著吸收率、临床症状改善率、空洞缩小闭合率分别为86.96(40/46)、93.48%(43/46)、80.00%(24/30),均高于对照组的69.57%(32/46)、73.91%(34/46)、53.57%(15/30),差异均有统计学意义(χ^(2)值分别为4.089、6.452、4.592,P值均<0.05)。治疗前两组的CD3^(+)、CD4^(+)、CD8^(+)计数、CD4^(+)/CD8^(+)比值差异均无统计学意义(Z=-1.581,P=0.114;Z=-0.719,P=0.472;Z=-0.633,P=0.527;Z=-0.397,P=0.691,P值均>0.05),治疗后两组均有所上升,但观察组患者的CD3^(+)、CD4^(+)、CD8^(+)计数、CD4^(+)/CD8^(+)比值上升水平显著高于对照组,差异均有统计学意义(Z=-2.151,P=0.031;Z=-5.038,P=0.001;Z=-2.024,P=0.043;Z=-2.139,P=0.032,P值均<0.05)。观察组中周围神经炎发生率为26.87%显著高于对照组的19.57%(χ^(2)=4.842,P<0.05),两组患者中胃肠道反应、肝损伤、血小板减少、贫血、肾功能异常发生率比较,差异均无统计学意义(P>0.05),但贫血和血小板减少也应引起重视,不良反应经对症治疗均缓解。结论强化期含Lzd的方案治疗MDR-TB患者,有助于提高早期痰菌及痰培养阴转率,降低传播性;提升患者T淋巴细胞亚群水平,改善免疫功能,提高疗效。监测并及时降阶梯给药可减少Lzd不良反应的发生。

Objective To explore the efficacy,immunological effect and safety of intensive phase containing Linezolid(Lzd)in treatment of multidrug-resistant tuberculosis(MDR-TB).Methods A total of 92 patients with multidrug resistant tuberculosis who were treated in our hospital from March 2017 to October 2019 were enrolled in the study.According to random number table method,all cases were divided into two groups,46 cases in the observation group,and 46 cases in the control group.The control group received the standard chemotherapy regimens,while the observation group added Lzd on the basis of treatment of the control group.The sputum negative conversion rate and sputum culture negative conversion rate were compared between the two groups at the end of 3 months and 6 months after treatment.As well as the significant absorptivity of lesion,clinical symptom improvement rate and closure rate of cavity reduction were compared at the end of 6 months.The difference of T lymphocyte subsets and the occurrence of adverse drug reactions were analyzed between the two groups before and after treatment.P<0.05 was considered that the difference was statistically significant.Results The rates of sputum negative conversion and sputum culture negative conversion at the end of 3 months and 6 months after treatment in the observation group[76.09%(35/46),91.30%(42/46),73.93%(34/46),91.30%(42/46)]were respectively higher than those in the control group[54.35%(25/46),73.91%(34/46),52.17%(24/46),71.74%(33/46)]with significant difference statistically(χ^(2)=4.792,P<0.05;χ^(2)=4.842,P<0.05;χ^(2)=4.665,P<0.05;χ^(2)=5.844,P<0.05).The rates of lesion absorption,clinical symptom improvement and cavity reduction at the end of 6 months after treatment in the observation group[86.96%(40/46),93.48%(43/46),80.00%(24/30)]were respectively higher than those[69.57%(32/46),73.91%(34/46),53.57%(15/30)]in the control group with significant difference statistically(χ^(2)=4.089,P<0.05;χ^(2)=6.452,P<0.05;χ^(2)=4.592,P<0.05).The CD3^(+),CD4^(+),CD8^(+)count and the ratio of CD4^(+)/CD8^(+)in the observation group and control group before treatment showed no statistical difference(Z=-1.581,P=0.114;Z=-0.719,P=0.472;Z=-0.633,P=0.527;Z=-0.397,P=0.691;P>0.05,respectively).The CD3^(+),CD4^(+),CD8^(+)count and the ratio of CD4^(+)/CD8^(+)were increased in the two group after treatment.The increase of CD3^(+),CD4^(+),CD8^(+)count and the ratio of CD4^(+)/CD8^(+)in the observation group were higher than those in the control group with significant difference(Z=-2.151,P=0.031;Z=-5.038,P=0.001;Z=-2.024,P=0.043;Z=-2.139,P=0.032;P<0.05,respectively).The incidence of peripheral neuritis in the observation group was(26.87%)significantly higher than that in the control group(19.57%,χ^(2)=4.842,P<0.05).The incidence of gastrointestinal reaction,liver damage,thrombocytopenia,anemia and abnormal renal function in the observation group and control group showed no significant difference(P>0.05).However,anemia and thrombocytopenia should also be taken seriously.Adverse reactions should be relieved by symptomatic treatment.Conclusion The treatment of MDR-TB patients with Lzd in the intensification stage is helpful to improve the early sputum bacteria and sputum culture negative conversion rate,and reduce the transmission,as well as improve the level of T lymphocyte subsets,immune function and curative effect.The incidence of Lzd adverse reactions can be reduced by monitoring and timely step-down administration.