S84 How good is Xpert MTB/XDR in drug resistant TB?

<h3>Background</h3> Drug resistant TB is a growing concern with 11.6% of laboratory confirmed cases being resistant to at least one first-line drug in England. Currently whole genome sequencing (WGS) still requires a positive culture before providing drug susceptibilities hence potentially introducing a delay of weeks. Xpert MTB/XDR (Cepheid, USA) is a rapid PCR test for identification of drug resistant TB including resistance to INH, fluoroquinolones, ethionamide and 2nd line injectables. This may provide an initial rapid result pending WGS to allow initiation of DR or MDR regimes. <h3>Aims</h3> To establish the limit of detection (LoD) of Xpert MTB/XDR using frozen MTB cultures with known resistance patterns. <h3>Methods</h3> This retrospective study in London used resistant clinical MTB cultures which were sub-cultured 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. Five strains were used to establish the LoD on Xpert MTB/XDR by performing seven ten-fold serial dilutions from 0.5 McFarland measured on a densitometer to a dilution of 10⁷. <h3>Results</h3> Fourteen clinical strains were verified on Xpert MTB/XDR and the same resistance patterns were correctly identified in 13 stains (93%) when compared to WGS. A discrepant result was found with fluoroquinolone resistance where low detection was identified on Xpert MTB/XDR but not on WGS. All INH resistance were correctly identified. The LoD across 5 strains using Xpert MTB/XDR varied between a four-fold (10⁴) to six-fold (10⁶) dilutions. Fluoroquinolone sensitivity patterns were an issue from a dilution of 10⁴ onwards with results reading ‘indeterminate’ or ‘low detected’ (figure 1). <h3>Conclusions</h3> Xpert MTB/XDR could be used as a tool to rapidly identify TB and drug susceptibilities. It identified all INH resistant cases and may be useful in PCR positive samples awaiting culture and WGS, allowing for the appropriate WHO regimens being started earlier for INH/MDR TB. Care must be taken with regards to indeterminate fluoroquinolone results as this may provide a false positive reading.