广州地区耐多药结核分枝杆菌MIRU-VNTR位点与耐药性变迁的关联研究

Relationship between MIRU-VNTR loci and drug resistance changes of multidrug-resistant Mycobacterium tuberculosis in Guangzhou

目的探讨广州地区耐多药结核分枝杆菌散在重复单元-数目可变串联重复序列(ycobacterial interspersed repetitive unit-variable number tandem repeat,MIRU-VNTR)与耐药性变迁的关系。方法对2011至2015年广州市胸科医院收治的36例耐多药结核病患者在治疗期间的多次分离培养株105株(2~8株不等)进行MIRU-VNTR分型,分析在治疗期间异烟肼、乙胺丁醇、链霉素、阿米卡星、左氧氟沙星和莫西沙星等耐药性有变化者与16个MIRU-VNTR位点多态性之间的相关性。耐药表型和VNTR位点之间的相关性使用χ^(2)检验。结果61.1%(22/36)的患者(69株)发生了耐药性变迁,其中异烟肼耐药表型变迁结核菌4株(5.8%),乙胺丁醇耐药表型变迁结核菌18株(26.1%),链霉素耐药表型变迁结核菌8株(11.6%),阿米卡星耐药表型变迁结核菌8株(11.6%),左氧氟沙星耐药表型变迁结核菌21株(30.4%),莫西沙星耐药表型变迁结核菌25株(36.2%)。耐药表型变迁百分率顺序:莫西沙星>左氧氟沙星>乙胺丁醇>链霉素/阿米卡星>异烟肼,6种耐药表型均存在菌株由敏感变为耐药或耐药变为敏感的情况。耐多药结核分枝杆菌的耐药变迁表型与VNTR位点的整体关联差异无统计学意义(P>0.05),耐药变迁表型无变化与具有4种耐药变迁表型变化的VNTR位点关联差异有统计学意义(P<0.05)。乙胺丁醇耐药表型-VNTR4348、链霉素耐药表型-VNTR0595、莫西沙星耐药表型-VNTR1907和莫西沙星耐药表型-VNTR1895差异均有统计学意义(均P<0.05)。结论耐多药结核病患者病原菌耐药性变迁与MIRU-VNTR多态性存在关联,具体机制尚待进一步研究。

Objective To investigate the relationship between Mycobacterial interspersed repetitive unit-variable number tandem repeat(MIRU-VNTR)and the changes of drug resistance in multi-drug resistant Mycobacterium tuberculosis in Guangzhou.Methods MIRU-VNTR typing was performed on 105 strains(2~8 strains)isolated from 36 patients with multidrug-resistant tuberculosis in Guangzhou Chest Hospital from 2011 to 2015.The correlation between the changes of drug resistance such as isoniazid,ethambutol,streptomycin,amikacin,levofloxacin and moxifloxacin during treatment and the polymorphism of 16 MIRU-VNTR loci was analyzed.The relationship between the drug-resistant types and VNTR loci was analyzed byχ^(2) test.Results Sixty-one point one percent(22/36)of the patients had drug resistance changes;among which,8 trains(5.8%)had isoniazid resistance changes,18(26.1%)had ethambutol resistance changes,8(11.6%)had streptomycin resistance changes,8(11.6%)had amikacin resistance changes,21(30.4%)had levofloxacin resistance changes,and 25(36.2%)had moxifloxacin resistance changes.The percentages of the phenotype changes were as below:moxifloxacin>levofloxacin>ethambutol>streptomycin/amikacin>isoniazid.All the six drug-resistant phenotypes showed that the strains changed from sensitive to resistant or from resistant to sensitive.There was no statistical difference in the correlation between the drug resistance change phenotype of multidrug-resistant Mycobacterium tuberculosis and the VNTR loci(P>0.05).There was a statistical difference in the correlation between the drug resistance change phenotype and the VNTR loci with four drug resistance change phenotypes(P<0.05).There were statistical differences in the ethambutol resistance phenotype-VNTR4348,streptomycin resistance phenotype-VNTR0595,moxifloxacin resistance phenotype-VNTR1907,and moxifloxacin resistance phenotype-VNTR1895(all P<0.05).Conclusion The results suggest that the change of drug resistance of pathogenic bacteria in patients with multidrug-resistant tuberculosis is associated with MIRU-VNTR polymorphism,but the specific mechanism remains to be further studied.