Prediction of drug resistance profile of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) isolates from newly diagnosed case by whole genome sequencing (WGS): a study from a high tuberculosis burden country.

Objectives: Our aim was to assess the ability of the Whole-genome sequencing (WGS) in predicting drug resistance profile of multidrug-resistant mycobacterium tuberculosis (MDR-MTB) from newly diagnosed cases in China.

Methods: We validated the Phenotypic drug Sensitivity Test (pDST) for 12 anti-tuberculosis drugs using the Bactec MGIT 960 system. We described the characteristics of the isolates enrolled and compared the pDST results with resistance profiles predicted by WGS.

Results: The pDST showed that of the 43 isolates enrolled, 25.6% were sensitive to rifabutin (RFB); 97.7%、97.7%、93.0% and 93.0% were sensitive to cycloserine (Cs), amikacin/kanamycin (Ak/Km), para-aminosalicylic acid (Pas) and ethionamide Eto), respectively; 18.6% were resistant to fluoroquinolones (FQs) or second-line injections. Genotype DST determined by WGS of Ak/Km、Eto and RFP reached high consistency to 97.7% compared with pDST, followed by moxifloxacin (Mfx) 95.3%, levofloxaci (Lfx) and Pas 93%, streptomycin (Sm) 90.3%. The genotype DST of RFB and EMB showed low consistency with the pDST of 67.2 and 79.1%. WGS also detected 27.9% isolates of pyrazinamide(PZA)-related drug-resistant mutation. No mutations associated with linezolid (Lzd), bedaquiline (Bdq) and clofazimine (Cfz) were detectd.

Conclusions: WGS has the potential to infer resistance profiles without time-consuming phenotypic methods, which could be provide a basis to formulate reasonable treatment in high TB burden areas.