Abstract

Introduction Whole Genome Sequencing (WGS) for the identification and resistance prediction of mycobacterium tuberculosis (MTB) has been developed and validated by Public Health England with the aim to improve patient management by providing faster more accurate diagnosis of tuberculosis (TB) from clinical samples and to quickly identify linked TB cases. WGS has been used in clinical practice in Birmingham, UK since December 2016. Here we present the results of the first year of WGS results used in clinical practice. Methods Consecutive cases of culture positive TB diagnosed at a hospital in Birmingham in 2014 prior to WGS implementation were compared to cases diagnosed in 2017 following WGS implementation. Time to culture and time to sensitivity profile were compared. Results 100 consecutive controls from 2014 and 82 cases from 2017 were included. The median time from the sample being taken to culture was 18 days (12–26) for controls and 19 days (13–23) for cases. Overall for phenotypic results there were 147 fully sensitive samples, 24 resistant samples and 10 fails. Amongst the WGS results there were 48 sensitive results, 24 unknowns, 4 resistant and 6 fails. The median time to a phenotypic result was 55 days (40–81) for controls and 55 days (39–79) for cases. The median time for a WGS result from taking the sample was 27 days (19–37), the median time from culture positivity to a WGS result was 7 days (5–11). For resistant samples median time to phenotypic result was 31 (21–52) days for sensitive samples and 45 (38–72) days for resistant samples. With WGS mean time to result for sensitive samples was 7 days (6–9) and for resistant samples 19 (7–24) days. Conclusion Early experience with WGS results has shown that results are quicker compared to phenotypic results especially where the MTB sample is resistant. Importantly in this real life setting resistance profiles were available whilst patients were still on initiation phase treatment with 4 drugs. WGS results include relatedness information allowing TB transmission to be detected and investigated. The WGS results are quicker than the previous typing methods which gave results long after phenotypic results and often after patients had competed treatment.

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