表型与分子药物敏感性试验对术后耐药骨关节结核患者化疗的指导与效果分析

doi:10.3969/j.issn.1000-6621.2020.08.011

摘要/Abstract

摘要：

目的评价在表型及分子药物敏感性试验(简称“药敏试验”)指导下,耐药骨关节结核患者术后个体化治疗的疗效。方法采用回顾性分析的方法,连续选取2018年3—12月在新疆维吾尔自治区胸科医院骨科接受病灶清除手术治疗的骨关节结核患者112例,对术中标本同时采用BACTEC MGIT 960和MTBDRplus-分子线性探针技术(LPA)进行药敏试验;表型及分子药敏试验联合检出耐药患者23例。根据药敏试验结果制定个体化药品治疗方案,并随访12个月,通过比较术前及随访期间的影像学、血红细胞沉降率、C-反应蛋白、疼痛视觉模拟评分系列预后指标来评价治疗效果。计量资料符合正态分布以“$\bar{x}$±s”表示,组间计量资料的比较采用重复测量方差分析;非正态分布的数据以中位数(四分位数)[M(Q₁,Q₃)]表示,组间比较采用Friedman检验;均以 P<0.05为差异有统计学意义。结果 23例耐药骨关节结核患者术后经个体化治疗12个月,好转21例,复发1例,失访1例;好转患者的植骨融合率为90.5%(19/21)。21例好转患者术前检测血红细胞沉降率平均为(62.62±26.52)mm/1h,C-反应蛋白平均为(52.29±22.40)mg/L,疼痛视觉模拟评分为7.0(6.0,7.5)分。经12个月的个体化治疗,血红细胞沉降率降至(14.39±5.24)mm/1h,与术前比较差异有统计学意义(t=-8.25,P=0.000);C-反应蛋白平均为(5.36±2.38)mg/L,与术前比较差异有统计学意义(t=-9.65,P=0.000),两项指标均已恢复至正常范围。疼痛视觉模拟评分降至1.0(0.0,1.0)分,疼痛症状得到极大的缓解,与术前评分比较差异有统计学意义(q=7.30,P=0.000)。结论在表型药敏试验的基础上辅以分子药敏试验,有利于全面、快速地制定抗结核药品的治疗方案,术后科学、规范的个体化抗结核药品治疗是治愈耐药骨关节结核的关键。

关键词: 结核, 骨关节, 结核, 抗多种药物性, 微生物敏感性试验, 药物疗法, 疗效比较研究

Abstract:

Objective To evaluate short-term effectiveness of individualized treatment under the guidance of phenotypic and molecular drug susceptibility tests(DST) for patients with drug-resistant osteoarticular tuberculosis. Methods Using retrospective analysis, 112 cases of osteoarticular tuberculosis patients who received focal cleaning operation were enrolled between March to December 2018 in Chest Hospital of Xinjiang Uyghur Autonomous Region. BACTEC MGIT 960 and MTBDRplus-LPA were used for conducting DST. There were 23 drug-resistant patients detected by phenotypic and molecular DST. We then developed individualized anti-tuberculosis drug treatment plans for patients with drug-resistant osteoarticular tuberculosis based on DST results, and followed them up for 12 months, comparing a series of prognostic indicators (Imaging, ESR, CRP, VAS) for preoperative and follow-up periods to evaluate the effectiveness of treatment. Measurement data with normal distribution was expressed as “ $\bar{x}$±s”, comparison between groups was tested using ANOVA of repeated measurement data. Non-normal distribution was represented by “Median (IQR)”, comparison between groups was done with Friedman test. Statistically significance was set at P<0.05. Results Among 23 drug-resistant patients who had received individualized treatment for 12 months after surgery, 21 patients got improved, 1 patient had relapsed, and 1 patient was lost to follow-up. The bone graft fusion rate of 21 improved patients was 90.5% (19/21); The average ESR of 21 improved patients before surgery was (62.62±26.52) mm/1 h, the average CRP was (52.29±22.40) mg/L, the average VAS score was 7.0(6.0-7.5) points. After 12 months of personalized treatment, the average ESR dropped to (14.39±5.24) mm/1 h, which was significantly different from that before surgery (t=-8.25,P=0.000); The average CRP was (5.36±2.38) mg/L, had statistically significant difference compared with preoperative period (t=-9.65,P=0.000). Both indicators had returned to the normal range. The average VAS score dropped to 1.0(0.0-1.0)points, showing that symptoms of pain were greatly relieved, and there was a statistically significant difference from the preoperative score (q=7.30,P=0.000). Conclusion Phenotypic DST detection combined with molecular DST detection could help us to rapidly develop a comprehensive anti-tuberculosis drug treatment regimen. Postoperative reasonable and well-followed individualized anti-tuberculosis drug treatment is the key measure to cure osteoarticular tuberculosis.

Key words: Tuberculosis, osteoarticular, Tuberculosis, multidrug-resistant, Microbial susceptibility tests, Drug therapy, Comparative effectiveness research

盛杰, 朱洋, 地里下提·阿不力孜, 唐伟, 古甫丁, 宋兴华. 表型与分子药物敏感性试验对术后耐药骨关节结核患者化疗的指导与效果分析[J]. 中国防痨杂志, 2020, 42(8): 838-844. doi: 10.3969/j.issn.1000-6621.2020.08.011

SHENG Jie, ZHU Yang, Dilixiati·Abulizi , TANG Wei, GU Fu-ding, SONG Xing-hua. Individualized treatment of drug-resistant osteoarticular tuberculosis based on phenotypic and molecular drug susceptibility tests and its short-term effectiveness evaluation[J]. Chinese Journal of Antituberculosis, 2020, 42(8): 838-844. doi: 10.3969/j.issn.1000-6621.2020.08.011

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例号	性别	年龄(岁)	患者类别	耐药谱	个体化抗结核药品治疗方案
1	女	29	复治	R、H	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
2	女	52	复治	R、H	6Mfx-Am-Lzd-Pto-Z-E/12~14Mfx-Pto-Z-E
3	女	65	复治	R、H	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
4	女	41	复治	R、H	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
5	男	17	初治	R	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
6	女	56	初治	H	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
7	女	31	复治	R	6Mfx-Am-Cs-Pto-Z/12~14Mfx-Cs-Pto-Z
8	男	31	复治	R、H	6Mfx-Am-Lzd-Pto-Z-E/12~14Mfx-Pto-Z-E
9	男	33	复治	R	6Mfx-Am-Lzd-Pto-Z-E/12~14Mfx-Pto-Z-E
10	男	22	初治	R、H	6Mfx-Cm-Cs-Pto-Z/12~14Mfx-Cs-Pto-Z
11	男	46	复治	R、H	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
12	女	27	初治	R、H	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
13	女	20	复治	R、H、Sm、Rft、Rfb	6Mfx-Cm-Cs-Pto-Z/12~14Mfx-Cs-Pto-Z
14	女	36	复治	R、H	6Lfx-Am-Lzd-Pto-Z/12~14Lfx-Pto-Z-E
15	女	55	复治	R、H	6Mfx-Am-Cs-Pto-Z/12~14Mfx-Cs-Pto-Z
16	女	44	复治	R、H、S、Rft、Rfb	6Lfx-Lzd-Cs-Pto-Z/12~14Lfx-Cs-Pto-Z
17	女	29	初治	R、H	6Mfx-Lzd-Cs-Pto-Z/12~14Mfx-Cs-Pto-Z
18	男	31	复治	R、H	6Lzd-Cfz-Cs-Am-Pto-Z/14~18Cfz-Cs-Pto-Z
19	女	44	复治	R、H	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
20	男	49	复治	R、H、Rft、Lfx	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
21	男	52	复治	R、H	6Lfx-Am-Lzd-Pto-Z-E/12~14Lfx-Pto-Z-E
22	男	46	初治	R、H	18~24R-Lfx-Z-E
23	男	76	复治	H、Sm	18~24R-Lfx-Z-E

检查时间	ESR(mm/1h)	CRP(mg/L)
术前	62.62±26.52^a	52.29±22.40^e
术后1个月	59.48±19.83^b	45.63±19.23^f
术后3个月	38.57±19.69^c	27.54±8.56^g
术后6个月	21.67±3.88^d	9.19±1.58
术后9个月	19.05±7.20	8.49±3.32
术后12个月	14.39±5.24	5.36±2.38
F值	34.84	54.08
P值	0.000	0.000

测评时间	VAS[分,M(Q₁,Q₃)]	χ²值	P值
术前	7.0(6.0,7.5)^a	79.40	0.000
术后1个月	3.0(2.0,4.0)^b
术后3个月	2.0(2.0,3.0)^c
术后6个月	1.0(1.0,2.0)
术后9个月	1.0(0.0,1.0)
术后12个月	1.0(0.0,1.0)