Application evaluation of whole-genome sequencing technology in predicting drug resistance of second-line injectable of anti-tuberculosis drugs / 中华检验医学杂志

ABSTRACT

Objective:To evaluate the clinical-application values of whole genome sequencing (WGS) technology to detect the drug resistance feature of second-line injectable drugs (SLIDs) for multidrug-resistant tuberculosis treatment.Methods:The proportional-method drug sensitivity test and the whole gene sequencing technology were used to simultaneously examine the resistance of three SLIDs kanamycin (Km) and Amikacin(Am) and capreomycin (Cm) in 172 multidrug-resistant tuberculosis (MDR) strains preserved in the strain bank of the Tuberculosis Laboratory of Shenzhen Chronic Disease Prevention and Control Center from 2013 to 2017. The proportional-susceptibility tests were considered as the gold standard to evaluate the sensitivity, specificity and consistency of WGS results. The samples with differences between the two methods were compared with the minimum inhibitory concentration detection method. The McNemar test was used to statistically analyze the detection rates of the two methods, and a P value<0.05 indicated the significant difference between two groups. Results:A total of 172 MDR strains were included in this study. Two mutated genes were identified by the WGS examination rrs and eis. Among these genes, rrs-A1401G mutation occurred in 58.3% in Am resistant strains, 14/18 in Km resistant strains or 14/14 in Cm resistant strains, respectively. The sensitivity, specificity and consistency of WGS predicted Am were 14/15, 93.6%, and 68.0%, 15/15, 98.1%, and 90.0% in Km, or 14/15, 100%, and 96.0% in Cm. There were 13 strains with inconsistent results by the two methods. One strain was retested by MIC as a drug-resistant strain and other 12 strains were sensitive. There were 11 strains with inconsistent Am test results, and WGS test results showed that 8 strains had rrs-514-A/C mutations, while DST and MIC tests were sensitive. Conclusion:WGS is enough is sensitive and specific for diagnosing SLIDs resistance.