耐多药肺结核患者基线菌株二线抗结核药物耐药情况分析

何贵清 施伎蝉 吴联朋 蒋贤高

[摘要] 目的 了解耐多药肺结核患者基线菌株对二线抗结核药物的耐药情况。 方法 随机选取从2016年3月～2017年5间本院收集的耐多药肺结核患者的基线52株，对其进行9种二线抗结核药物的敏感性进行试验，分析对不同药物耐药比例以及同类药物交叉耐药情况。 结果 9种二线抗结核药物中，耐药比例顺位依次为氧氟沙星=左氧氟沙星（均占59.6%，31/52）>莫西沙星（占30.8%，16/52）>阿米卡星=卡那霉素（均占9.6%，5/52）>对氨基水杨酸=环丝氨酸（均占7.7%，4/52）>卷曲霉素=丙硫异烟胺（均占5.8%，3/52）。氧氟沙星和左氧氟沙星呈完全交叉耐药，与莫西沙星交叉耐药比例占51.6%（15/31）；阿米卡星和卡那霉素呈完全交叉耐药，与卷曲霉素交叉耐药占60%。 结论 耐多药肺结核患者基线菌株对氟喹诺酮类药物耐药严重，其他二线抗结核药物亦存在不同程度耐药。因此，在制定起始有效耐多药结核治疗方案前应完善二线药物敏感性试验。

[关键词] 分枝杆菌；结核；二线药物；药物敏感性试验；耐多药结核

[中图分类号] R521 [文献标识码] B [文章编号] 1673-9701（2018）15-0084-04

Analysis of drug resistance of second-line anti-TB drugs to baseline strain in patients with multidrug-resistant pulmonary tuberculosis

HE Guiqing1 SHI Jichan1 WU Lianpeng2 JIANG Xiangao1

1.Department of Infectious Diseases，Wenzhou City Central Hospital in Zhejiang Province，Wenzhou 325000，China； 2.Department of Laboratory，Wenzhou City Central Hospital in Zhejiang Province，Wenzhou 325000，China

[Abstract] Objective To investigate the resistance of second-line anti-TB drugs to baseline strain in patients with multidrug-resistant pulmonary tuberculosis. Methods A total of 52 baseline strains in patients with multidrug-resistant pulmonary tuberculosis collected from March 2016 to May 2017 in our hospital were randomly selected. The sensitivity of the nine kinds of second-line anti-TB drugs was tested， to analyze the proportion of different drug resistance and cross-resistance of similar drugs. Results Among the 9 second-line anti-TB drugs， the ratio of drug resistance was ofloxacin=levofloxacin（59.6%， 31/52）>moxifloxacin（30.8%， 16/52）> amikacin=kanamycin（both 9.6%， 5/52）>p-aminosalicylic acid=cycloserine（both 7.7%， 4/52）> capreomycin =prothionamide（both 9.6%，3/52）. Ofloxacin was completely cross-resistant with levofloxacin， and its cross-resistant rate with moxifloxacin accounted for 51.6%（15/31）. Amikacin was completely cross-resistant with kanamycin， and its cross-resistant rate with capreomycin accounted for 60%. Conclusion The baseline strains of patients with multi-drug resistant pulmonary tuberculosis are seriously resistant to fluoroquinolones. There is resistance to some extent for other second-line anti-tuberculosis drugs. Therefore， second-line drug susceptibility testing should be completed prior to establishing an effective MDR-TB treatment regimen.

[Key words] Mycobacterium； Tuberculosis； Second-line drugs； Drug susceptibility testing； Multidrug-resistant tuberculosis

全球耐多藥结核病形式严峻，疗程长，需联合4～5种药物，不良反应大，传统WHO推荐长疗程方案至少大于20个月，导致患者难以坚持，在真实世界里，治疗成功率不足50%，提示缩短疗程势在必行。值得可喜的是孟加拉等国短程治疗方案治疗成功率显著高于传统长疗程方案[1-3]，促使2016 WHO制定了耐多药结核病短程方案并向全世界推广[4]，但由于是非随机对照研究，询证学依据尚不充分。特别国内耐多药结核病基线菌株的Pre-XDR和XDR-TB比例较高[5-6]，当前盲目推广短程方案未必可行，可能因治疗不充分势必造成更多药物耐药，需及时完善二线抗结核药物敏感性试验制定合理方案。国内耐多……