84株广泛耐药结核分枝杆菌对新型氟喹诺酮类药物的耐药情况分析  

Resistance Analysis of 84 Extensively Drug-resistant Mycobacterium tuberculosis Isolates against Three New Generation Fluoroquinolones

作　　者：宗兆婧[1] 荆玮[1] 霍凤敏[1] 董玲玲[1] 马异峰 逢宇[1] 黄海荣[1] 

机构地区：[1]首都医科大学附属北京胸科医院北京市结核病胸部肿瘤研究所国家结核病临床实验室,101149

出　　处：《结核病与胸部肿瘤》2017年第4期274-279,共6页Tuberculosis and Thoracic Tumor

摘　　要：目的研究广泛耐药结核分枝杆菌临床分离株对新型氟喹诺酮类药物的耐药特征以及氟喹诺酮类药物耐药相关基因突变的特点。方法选取2012年4月至2014年4月在北京胸科医院住院治疗的84例广泛耐药结核病患者的临床分离菌株，应用微孑L板阿尔玛蓝显色法（micro．platealamarblueassay，MABA）检测菌株对左氧氟沙星、莫西沙星和加替沙星的最小抑菌浓度（minimum inhibitoryconcentration，MIC），所有菌株都进行了∥州基因和gyrB基因的耐药决定区（QRDR）的序列测定。结果84株广泛耐药结核分枝杆菌临床分离株经MABA检测。分别以1μg／ml、2μg／ml、1μg／ml作为耐药判读标准，左氧氟沙星、莫西沙星、加替沙星3种氟喹诺酮类药物的耐药率分别是88．1％（74／84）、44．0％（37／84）、61．9％（52／84o89．3％（75／84）的临床分离株发生了∥州基因耐药决定区突变，其中以第94位点突变最为常见，Asp94Gly突变菌株的MIC值较高，而所有菌株的gyrB基因均为野生型。结论广泛耐药结核分枝杆菌对新型氟喹诺酮类药物耐药形势严峻，耐药基因突变形式以∥叫基因突变为主，第94位点的Asp94Gly突变可能和高水平耐药有关。Objective To investigate the resistant status of extensively drug-resistant Mycobacterium tuberculosis isolates against new genratation flnroquinolones （FQs）. Methods Extensively drug-resistant Mycobacterium tuberculosis （XDR-MTB） clinical isolates were collected from Beijing Chest Hospital between 2012-2014. Absolute concentration method was used for ofloxacin （Ofx） and levofloxacin （Lfx） susceptibility testing, while broth dilution method was used to detect the minimal inhibitory concentration （MIC） of the isolates against three FQs, including Lfx,moxifloxacin （Mfx） and gatifloxacin （Gfx）. The quinolone resistance determining regions （QRDR） ofgyrA and gyrB were sequenced for all the enrolled isolates. Results A total of 84 XDR-MTB isolates were enrolled. Among them,74 （74/84, 88. 1%）, 37 （37/84,44. 0%） and 52 （52/84, 61.9%） isolates were resistant to Lfx, Mfx and Gfx according the cut-off criteria recommended by WHO, respectively. Mutations at 88, 90, 91 and 94 locus of gyrA were detected among 89. 3% （75/84） of the enrolled isolates, and Asp94Gly accounting for high-level FQs resistance. All the strains had wild type gyrB. Conclusion Our findings demonstrated that new generation FQs resistance were very frequently observed among XDR-MTB isolates, and mutation within QRDR of gyrA was the main mechanism of FQs resistance.

关 键 词：泛耐药结核病 分枝杆菌 结核 喹诺酮类 微生物敏感性试验 多药耐药相关蛋白质类 点突变 

分 类 号：R520.4[医药卫生—内科学]