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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
  1. Alje PVan Dam1,
  2. Carolien M Wind2,
  3. Mirjam Dierdorp1,
  4. Ikram Belhacen1,
  5. Myrthe De Laat2,
  6. Maarten Schim Van Der Loeff3,
  7. Henry JC De Vries2,
  8. Sylvia M Bruisten1
  1. 1Public Health Laboratory, Amsterdam Health Service, Amsterdam, The Netherlands
  2. 2STD Outpatient Department, Amsterdam Health Service, Amsterdam, The Netherlands
  3. 3Department of Infectious Diseases, Amsterdam Health Service, Amsterdam, The Netherlands

Abstract

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 <0.032 mg/L), frequency matched for year of isolation and sexual background. NG-MAST, MLVA and 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.

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