P28

Whole-genome sequencing (WGS) offers unprecedented resolution for tracking Mycobacterium tuberculosis transmission and antibiotic-resistance spread. Still, the establishment of standardized WGS-based pipelines and the definition of epidemiological clusters based on genetic relatedness are under discussion. Our current WGS-based surveillance strategy, implemented in the National Reference Laboratory for Tuberculosis (NRL-TB) of the Portuguese National Institute of Health since 2018 and relying on freely available software, performs both dynamic gene-by-gene (i.e., wgMLST) and SNP-based approaches for genetic cluster analysis towards epidemiological surveillance, while also reporting all MTB resistance-associated genetic markers. Here we present the results of the current MTB genomic surveillance of more than 300 isolates from 2012 up to 2021, focused on MDR/RR cases and specific episodes pinpointed by Public Health Authorities. Notwithstanding, the approach is being extended to contemplate all strains isolates in the NRL, in order to fully perform epidemiological and resistance diagnosis by WGS. Our current genomic dataset comprises 136 MDR/RR/Pre-XDR/XDR strains, 162 sensitive and the remaining are resistant to one or more antibiotics. As expected, the majority of our isolates belong to lineage4 (~300), specifically to lineages 4.3.2.1 (31.7%) and 4.3.2.2 (19.0%). Genomic clustering by both approaches was shown to be consistently concordant and the analysis of retrospective genetic clusters, with epidemiological confirmed linkage, has allowed the definition of genetic distance threshold ranges to flag possible transmission chains. In summary, the implement WGS-based strategy has allowed both to routinely diagnose MTB resistance profiles for clinical purposes and to promote a more focused epidemiological investigation by Public Health Authorities.