P141 Quinolone-containing treatment-shortening regimens for tuberculosis: what are the implications for the NHS?

<h3>Introduction</h3> Recent trial data have demonstrated that both Drug-sensitive (DS) and Drug-resistant (DR) tuberculosis (TB) can be treated effectively with short-course quinolone-containing combination therapy. Current WHO guidance includes using a four-month treatment with quinolones throughout for DS TB. The adverse event profile of quinolones is well-recognised, however less is known about the prevalence of quinolone resistance, in particular when used to treat otherwise DS TB. The routine use of <i>M tuberculosis</i> complex Whole Genome Sequencing (WGS) in England, provides an opportunity to explore this in both DS and DR TB. <h3>Methods</h3> WGS isolate data for <i>M tuberculosis</i> complex between 2017 and 2023 were obtained from NMRS-North and Central (N &amp; C) and NMRS-South (S) UKHSA laboratories. After data cleaning, analyses were performed separately and then combined (data presented here). These focused on the relationship between quinolone, isoniazid and rifampicin resistance. <h3>Results</h3> Isoniazid resistance was present in 7.9% of 15350 isolates. Rifampicin or Rifampicin + Isoniazid resistance was seen in 2.1%, and WGS quinolone resistance was detected in 1.5% of. However, a greater proportion of WGS results for quinolones showed a mutation of uncertain significance (‘unknown’) than for other drugs (table 1, with all NMRS data combined and Isoniazid WGS profile included for comparison, percentages are for each row). Reassuringly, on phenotypic testing only 4/1021 (0.4%) NMRS-S isolates reported as ‘unknown’ on WGS were quinolone resistant. Column 3 of table 1 shows that quinolone resistance was present in 1% and 7.5% of Isoniazid DS and DR isolates. <h3>Discussion</h3> Quinolone-resistant <i>M tuberculosis</i> is present at a low though detectable frequency in all TB populations. The large number of WGS unknown results for quinolones that require further phenotypic testing is an additional time and financial cost that needs to be considered when implementing programmatic short-course treatment to adults with drug sensitive TB in the UK.