Study On Drug Sensitive Spectrum Of Multidrug-resistant Mycobacterium Tuberculosis And Its Correlation With Genotypes In China

Objective:To investigate the drug sensitivity spectrum of multidrug resistant?MDR?Mycobacterium tuberculosis?M.tuberculosis?and its correlation with genotypes for providing the scientific evidence of tuberculosis?TB?control strategy and more effective clinical therapy.Method:In this study,327 clinical M.tuberculosis isolates collected previously were used to detect the drug sensitivity to 17 clinical common drugs icluding the first and second-line anti-tuberculous drugs by means of the microplate susceptibility method and BACTEC^TMM MGIT960^TMM liquid culture method to determine their MIC.At the meanwhile,the genotypes were identified by single nucleotide polymorphisms?SNPs?typing technique.The drug cross resistance of M.tuberculosis and correlation between drug resistance and genotypes were analyzed.The comparison of counting data between two groups was analyzed with�?²�test and the difference was statistically significant?P<0.05?.Results:The resistance rates were higher to INH,RIF,SM,KAN and AMI,while the MIC values of LZD,BDQ,CAP and EMB resistant strains were mainly near the cut-off value.In this study,193 MDR-TB strains were highly resistant to 15 anti-MTB drugs other than INH and RIF,The drug resistance rates?from high to low?were RFB?83.42%?,SM?69.95%?,PZA?47.67%?,EMB?37.82%?,OFL?30.05%?,MOX?27.98%?,PAS?15.03%?,KAN?15.03%?,ETO?14.51%?,AMI?11.92%?,LZD?10.88%?,CAP?9.84%?,CYC?8.29%?,CFZ?4.15%?,and BDQ?3.11%?.With significant statistical differences?P<0.05?,the resistance rates of MDR strains to RFB,SM,PZA,EMB,OFL,MOX,PAS,KAN,ETO,AMI and CYC were significantly higher than that of non-MDR strains.Among the 193 MDR-TB strains,57 were pre-XDR strains and 22 were XDR-TB strains,accounting for 29.53%and 11.40%,respectively.The association analysis show that the cross-resistance rate to RIF and RFB was 83.42%,with a correlation coefficient of 0.80?>0.70?.The difference of RIF resistance rates between diverse levels of anti-drug groups was statistically significant??²=45.212,P<0.05?;This correlation were also observed between OFL and MOX,KAN and AMI,CFZ and BDQ,of which the cross-resistance rate was93.10%,75.86%and 40.00%,and correlation coefficients of 0.95,0.83,and 0.56,respectively,with high degree of correlation.Among the 193 MDR-TB strains,149 were Beijing genotypes?77.20%?,44 were non-Beijing genotypes?22.80%?;Among 149 strains of Beijing genotypes,66 strians?44.30%?belonged to Beijing classical genotypes,and 83 strains?55.70%?were modern Beijing genotypes.The resistance rate of Beijing genotype strains to streptomycin were significantly higher than that of non-Beijing genotypes??2=16.266,P=0.000?;while the resistance rates of non-Beijing genotype to OFL and MOX were significantly higher than that of Beijing genotypes??²=4.674,P=0.031 and?²=4.728,P=0.030?;the resistance rates of modern Beijing genotype strains to CYC,EMB,ETO,KAN,OFL,MOX and AMI were significantly higher than that of classical Beijing genotypes(?²_CYC=4.825,P_CYC<0.05;?²_EMB=4.279,P_EMB<0.05;?²_ETO=6.315,P_ETO<0.05;?²_KAN=4.866,P_KAN<0.05;?²_OFL=7.45,P_OFL<0.05;?²_MOX=7.162,P_MOX<0.05??²_AMI=8.23,P_AMI<0.05).Conclusion:In this study,the resistance of MDR-TB strains to17 first-line and second-line anti-tuberculosis drugs were tested by microporous plate method and BACTEC MGIT 960 liquid culture method.This research provides significant reference for drug-screening in clinical practice,formulation of TB therapies,development of specific prevention and control strategies and even prevention of its transmission and prevalence.