结核性脑膜炎临床分离株表型耐药特点及其治疗效果研究

doi:10.3969/j.issn.1000-6621.2015.04.006

中国防痨杂志 ›› 2015, Vol. 37 ›› Issue (4): 353-359.doi: 10.3969/j.issn.1000-6621.2015.04.006

结核性脑膜炎临床分离株表型耐药特点及其治疗效果研究

王婷赵雁林逄宇冯国栋宋媛媛欧喜超彭晋湘赵钢战丽萍注：王婷和赵雁林为并列第一作者

650051 昆明医科大学附属延安医院神经内科（王婷、战丽萍）；第四军医大学西京医院神经内科［王婷（研究生）、冯国栋、赵钢］；中国疾病预防控制中心结核病预防控制中心国家参比实验室（赵雁林、逄宇、宋媛媛、欧喜超）；解放军第四七八医院空勤科(彭晋湘)

收稿日期:2015-02-16 出版日期:2015-04-10 发布日期:2015-04-03
通信作者: 战丽萍；赵钢 E-mail:2510765864@qq.com；zhaogang@fmmu.edu.cn
基金资助:
“十二五”国家科技重大专项(2012ZX10003004)

Studies on the phenotypically resistant characteristics and therapeutic effect of antitubercular drugs on M. tuberculosis clinical isolates from the patients with tuberculous meningitis

WANG Ting, ZHAO Yan-lin, PANG Yu, FENG Guo-dong, SONG Yuan-yuan, OU Xi-chao, PENG Jin-xiang, ZHAO Gang, ZHAN Li-ping

Department of Internal Medicine, Yan’an Hospital Affiliated to Kunming Medical University, Kunming 650200, China

Received:2015-02-16 Online:2015-04-10 Published:2015-04-03
Contact: ZHAN Li-ping；ZHAO Gang E-mail:2510765864@qq.com；zhaogang@fmmu.edu.cn

摘要/Abstract

摘要： 目的研究分析结核性脑膜炎(tuberculous meningitis, TBM)的致病菌对抗结核药的耐药特点及抗结核药对致病菌的治疗效果。方法 500例疑似TBM患者脑脊液标本经MGIT（mycobacteria growth indicator tube）960液体培养出25株临床分离株，再用16S rRNA基因测序法进行菌种鉴定。继而对这25株结核分枝杆菌临床分离株分别进行14种抗结核药物的MGIT 960液体药敏试验和12种抗结核药物的传统比例法固体药敏试验、16种抗结核药物的最低抑菌浓度（MIC）测定。通过计算血药浓度峰值（C_max）/MIC值的大小来判断药物对菌株杀菌率的高低，并由此推断药物对该致病菌的治疗效果。结果液体药敏试验结果和固体药敏试验结果均显示了任意耐药的TBM临床分离株有13株（13/25）, 耐多药的TBM临床分离株有3株（3/25）；利福平、莫西沙星、左氧氟沙星、氯法齐明、对氨基水杨酸的C_max/MIC值分别为19.880、63.333、19.149、75.000、50.855。结论莫西沙星、氯法齐明、对氨基水杨酸、左氧氟沙星、利福平的C_max/MIC值较高，提示临床上使用高剂量利福平和氟喹诺酮类药物联合治疗TBM可以提高疗效；对氨基水杨酸和氯法齐明对耐多药TBM临床分离株可能有较好效果。

关键词: 结核, 脑膜/药物疗法, 表型, 微生物敏感性试验, 治疗结果

Abstract: Objective To study the phenotypically resistant characteristics and therapeutic effect of antitubercular drugs on M. tuberculosis clinical isolates from the patients with tuberculous meningitis (TBM). Methods Five hundred cerebrospinal fluid (CSF) from suspected patients with tuberculous miningitis were cultured with Bactec MGIT 960. Twenty-five strains were isotated, and then identified the species by 16S rRNA gene sequencing, detected 14 anti-tuberculous drug susceptibility by Bactec MGIT 960 and 12 anti-tuberculous drug susceptibility by the proportional method of conventional solid culture. The minimal inhibitory concentrations (MICs) of 16 anti-tuberculous drugs on these isolates were determined. The bacterial sterilization rate was determined by calculating the ratio of maximal plasma concentration (C_max)/MIC to evaluated thetherapeutic effect of drugs on M. tuberculosis. Results Of 25 M. tuberculosis isolates, 13 were resistant to any anti-tuberculous drugs, 3 were multidrug-resistant. The ratios of C_max/MIC for rifampicin, moxifloxacin, levofloxacin, clofazimine, and p-aminosalicylic acid were 19.880, 63.333, 19.149, 75.000, and 50.855, respectively. Conclusion Most drug-resistant isolates from TBM patients were phenotypically resistant to isoniazid or rifampicin, the least isolates were phenotypically resistant to quinolone. The C_max/MIC values of moxifloxacin, clofazimine, p-aminosalicylic acid, levofloxacin and rifampicin were higher, suggesting that the combination of high doses of rifampicin and fluoroquinolones might improve the therapeutic effect of TBM. P-aminosalicylic acid and clofazimine might play an better role in antituberculous treatment of TBM.

Key words: Tuberculosis, meningeal/drug therapy, Phenotype, Microbial sensitivity tests, Treatment outcome

王婷，赵雁林，逄宇，冯国栋，宋媛媛，欧喜超，彭晋湘，赵钢，战丽萍. 结核性脑膜炎临床分离株表型耐药特点及其治疗效果研究[J]. 中国防痨杂志, 2015, 37(4): 353-359. doi: 10.3969/j.issn.1000-6621.2015.04.006

WANG Ting, ZHAO Yan-lin, PANG Yu, FENG Guo-dong, SONG Yuan-yuan, OU Xi-chao, PENG Jin-xiang, ZHAO Gang, ZHAN Li-ping. Studies on the phenotypically resistant characteristics and therapeutic effect of antitubercular drugs on M. tuberculosis clinical isolates from the patients with tuberculous meningitis[J]. Chinese Journal of Antituberculosis, 2015, 37(4): 353-359. doi: 10.3969/j.issn.1000-6621.2015.04.006

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结核性脑膜炎临床分离株表型耐药特点及其治疗效果研究

Studies on the phenotypically resistant characteristics and therapeutic effect of antitubercular drugs on M. tuberculosis clinical isolates from the patients with tuberculous meningitis

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