LB1.67 Reduced susceptibility to ceftriaxone in neisseria gonorrhoeae in the netherlands recently predominantly found in association with an a501v/t mutation in the pena gene

Introduction Neisseria gonorrhoeae (NG) resistance to ceftriaxone interferes with effective treatment of gonorrhoea. Ceftriaxone-resistant NG isolates have not yet been isolated in the Netherlands, but strains with reduced susceptibility to ceftriaxone (CTR-RS) have been cultured. Methods We compared 141 CTR-RS NG strains (MIC ≥0.064 mg/L) isolated between 2009 and September 2015 with 142 susceptible control strains (MIC penA sequencing was performed for all strains. MLVA was also done for 25 additional CTR-RS strains isolated up to September 2016. Results CTR-RS strains originated more frequently from tonsils (23%) in comparison to controls (6%). CTR-RS strains had more often a mosaic penA gene (n=63, 45%), an A501V/T mutation (n=65, 46%) or a P551S mutation (n=8, 6%, not including 12 strains with double mutations at A501 and P551). These characteristics were found in only 6 (4%), 6 (4%) and 0 controls, respectively. Using MLVA, CTR-RS strains were more frequently found in clusters than controls (60% vs 23%). Eleven clusters were identified, of which 3 only and 5 mainly included CTR-RS strains. Three clusters consisted of controls only. Of the 3 largest CTR-RS clusters, 2 consisted of strains with a mosaic penA gene (almost all isolated before 2013), and 1 of strains with an A501T mutation (often isolated since 2013). Predominant NG-MAST genogroups among CTR-RS strains were G1407 (n=47, 37%) and G2400 (n=37, 27%). Of the 25 CTR-RS strains isolated after September 2015, only 1 clustered with mosaic penA strains, 14 grouped in other clusters, including 3, which clustered with previously isolated controls. Ten strains did not cluster. Conclusion CTR-RS strains isolated before 2013 mainly contained the penA mosaic gene. More recently, a A501V/T mutation is often found. CTR-RS strains can appear in clusters of susceptible strains, illustrating that genetic antimicrobial resistance development can occur independently of divergence of the background genome.