P172 The mosaic mtr locus as major genetic determinant of azithromycin resistance of Neisseria gonorrhoeae, Germany, 2018

Abstract

<h3>Background</h3> Azithromycin resistant Neisseria gonorrhoeae (NG) isolates increased from 4.3% in 2016 to 9.2% in 2018 within the German Gonococcal Resistance Network (GORENET) NG sample collection. Using whole genome sequencing (WGS) of NG isolates in combination with clinical and epidemiological data, we aim to understand this observed increase. <h3>Methods</h3> GORENET was set up in 2013 as a laboratory network to monitor NG infections in Germany by collection of NG isolates, epidemiological and clinical data. In 2018, isolates with reduced susceptibility to azithromycin (MIC ≥ 0.25 mg/L) were analyzed by WGS followed by assignment of sequence types based on NG multiantigen sequence typing (NG-MAST) and multilocus sequence typing (MLST), detection of antimicrobial resistance determinants and generation of a core SNP distance-based neighbor-joining phylogenetic tree. Comparison with published isolates was performed based on a custom ad-hoc cgMLST scheme and calculation of a minimum spanning tree. <h3>Results</h3> Whole genome phylogenetic analyses resulted in 4 major clades corresponding to NG-MAST genogroups G2400, G3779 (G1407), G5441 and G12302. The clade comprising G12302 accounted for the majority of isolates with azithromycin resistance (MIC &gt; 0.5 mg/L) and was characterized by the presence of the recently described Neisseria lactamica-like mosaic mtr locus. In addition, strains in this clade were significantly associated with rectal infection site and younger age. Comparison with published isolates revealed similarity between a US and a German isolate of MLST ST9363 (12 nucleotides difference) and between a US and a German isolate of MLST ST11422 (21 nucleotides difference). <h3>Conclusion</h3> Our data indicate the recently observed increase in isolates resistant to azithromycin in Germany coincides with clonal expansion of NG-MAST genogroup G12302 and suggest that, together with horizontal gene transfer of resistance determinants and well-established point mutations, international spread of resistant lineages plays a major role regarding azithromycin resistance in Germany.