167株耐多药结核分枝杆菌药物敏感谱分析

Analysis on drug sensitivity spectrum of 167 multidrug-resistant Mycobacterium tuberculosis in China

目的了解耐多药结核分枝杆菌的药敏谱,为耐多药结核病(MDR-TB)的临床药物选择和防控提供科学依据。方法选取既往收集的MDR-TB 167株,采用lysX基因测序方法进行基因分型,并采用微孔板药敏法及BACTECTM MGIT 960TM液体培养法对其进行13种抗结核药物的敏感性检测,分析不同基因型MDR-TB菌株与耐药表型的相关性及药物交叉耐药情况。采用χ^2检验比较计数资料组间差异。结果167株MDR-TB菌株对除异烟肼、利福平外11种抗结核药物总耐药率为95.81%,准广泛耐药结核病(pre-XDR)比例为31.14%(52/167),广泛耐药结核病比例为6.59%(11/167)。北京基因型中链霉素耐药率高于非北京基因型,差异有统计学意义(χ^2=30.682,P<0.05),非北京基因型中pre-XDR比例高于北京基因型,差异有统计学意义(χ^2=5.332,P<0.05);氧氟沙星耐药率和吡嗪酰胺耐药率在现代北京基因型与古典北京基因型中差异有统计学意义(χ^2=4.105和χ^2=3.912,P<0.05)。利福平与利福布汀存在交叉耐药,交叉耐药率为86.23%,且不同程度利福平耐药组间利福布汀耐药率差异有统计学意义(χ^2=45.912,P<0.05)。氧氟沙星耐药与莫西沙星耐药有相关性、阿米卡星耐药与卡那霉素耐药有相关性,r分别为0.87和0.91。结论MDR-TB菌株对11种抗结核药物呈高度耐药,且同类型药物之间交叉耐药较为严重;北京基因型菌株是MDR-TB的主要流行菌株,与链霉素耐药高度相关。

Objective To investigate the drugs-sensitivity spectrum of multidrug-resistant tuberculosis(MDR-TB)in China and provide a scientific evidence for the drug selection in clinical therapy and the control of MDR-TB.Methods A total of 167 strains of MDR-TB were included in this study.Every strain was genotyped by lysX gene sequencing and their sensitivity to 13 different anti-TB drugs was tested by using MicroDSTTM and BACTECTM MGIT 960TM liquid-culturing method.The association between drug resistance and genotypes as well as cross drug resistance was also analyzed.The results were analyzed by means of the comparison of enumeration data between two groups withχ^2 test.Results The overall resistance rate of 167 MDR-TB strains to 11 anti-TB drugs,except isoniazide and rifampicin,was 95.81%,the rates of pre-extensive drug-resistance(pre-XDR)and extensive drug-resistance were 31.14%(52/167)and 6.59%(11/167),respectively.The streptomycin resistance rate of Beijing genotypes was significantly higher than that of the non-Beijing genotypes(χ^2=30.682,P<0.05),while the pre-XDR proportion in Beijing genotypes was lower than that in non-Beijing genotypes(χ^2=5.332,P<0.05).The resistance rates of Ofloxacin and Pyrazinamide in the modern Beijing genotype were significantly higher than those in classical ones(χ^2=4.105 andχ^2=3.912,P<0.05).In addition,the cross-resistance rate to rifampicin and rifabutin was 86.23%.A significant difference in drug-resistance rate to rifabutin was seen among groups with different levels of rifampicin resistance(χ^2=45.912,P<0.05).There was positive correlation not only between ofloxac resistance and moxifloxac resistance,but also between amikacin resistance and kanamycin resistance,with the coefficient of 0.87 and 0.91,respectively.Conclusions In this study,we observed that there were high incidences of the resistance to 11 anti-TB drugs in 167 clinical MDR-TB strains and the cross resistance phenomena between drugs of the same type were quite serious.The majority of MDR-TB strains belonged to Beijing genotype,which was highly associated with streptomycin resistance.