Comparing drug susceptibility testing for drug resistant TB using TB PCR and WGS

<b>Background:</b> With growing concerns for drug resistant TB especially isoniazid (INH) resistance, early identification of TB and drug susceptibilities are essential. WGS still requires culture before availability of drug susceptibilities, taking weeks. Xpert MTB/XDR (Cepheid, USA) could provide a tool for early identification of drug resistant TB including INH, fluoroquinolones, ethionamide and 2nd line injectables. <b>Aims:</b> Verification of Xpert MTB/XDR using frozen MTB cultures with known resistance. <b>Methods:</b> This retrospective study in London used resistant MTB cultures which were subcultured in 7H9 media and incubated for 7 days. 500µl of the culture positive broth for each strain was tested using Xpert MTB/XDR following the Cepheid GeneXpert SOP. Resistance patterns for each stain were compared to the genotypic susceptibilities using PhyRes SE, an online software for WGS analysis. <b>Results:</b> Of the 14 clinical isolates, the same resistance patterns were correctly identified in 13 stains (93%) for both Xpert MTB/XDR and WGS. The discrepant result was with fluoroquinolone resistance where low detection was identified on Xpert MTB/XDR but not on WGS. All INH resistance were correctly identified. <b>Conclusions:</b> Xpert MTB/XDR identified all INH resistant cases and may potentially be used as a rapid local diagnostic pathway in PCR positive samples pending culture and WGS, hence allowing appropriate WHO regimens being started earlier for INH/MDR TB.