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Oral Presentations
O04 – ANTIMICROBIAL RESISTANCE IN STI PATHOGENS
Monday, July 15, 2019 4:15 PM – 5:45 PM
O04.2 Phylogenomic analysis reveals persistence of neisseria gonorrhoeae clades with reduced susceptibility to cephalosporins
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  1. Jesse Thomas1,
  2. A Jeanine Abrams-Mclean2,
  3. Sandra Seby1,
  4. Matthew Schmerer1,
  5. Cau Pham3,
  6. Jaeyoung Hong3,
  7. Sancta St Cyr1,
  8. Kim Gernert1,
  9. Brian Raphael1,
  10. Ellen Kersh2,
  11. Antibiotic Resistant Laboratory Network4
  1. 1US Centers for Disease Control and Prevention, Division of STD Prevention, Atlanta, USA
  2. 2Centers for Disease Control and Prevention, Atlanta, USA
  3. 3Centers for Disease Control and Prevention, Division of STD Prevention, Atlanta, USA
  4. 4Antibiotic Resistant Laboratory Network, Washington/Maryland, USA

Abstract

Background The emergence of Neisseria gonorrhoeae strains with reduced susceptibility to the extended-spectrum cephalosporins (ESCs) cefixime and ceftriaxone has raised concerns over a future of untreatable gonorrhea. In 2015, a treatment regimen consisting of ceftriaxone and azithromycin were recommended to assist in delaying the further selection of resistant strains, including those with elevated cephalosporin minimum inhibitory concentrations (MICs) (ESCem). Recently, we conducted a retrospective study to assess the genetic relatedness of isolates in the United States from 2006–2017, and describe the emergence and dissemination of ESCem lineages over time.

Methods We examined the genomes of 637 N . gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project (GISP), including 317 isolates with elevated cefixime MICs (CFXem; MIC ≥ 0.25 μg/mL), 96 isolates with elevated ceftriaxone MICs (CROem; MIC ≥ 0.125 μg/mL), and 224 accompanying cephalosporin-susceptible isolates matched by region and collection date. We generated a core-genome SNP phylogeny, and examined the distribution of antimicrobial determinants known to be associated with cephalosporin resistance.

Results The majority of gonococcal isolates with elevated MICs to either cephalosporin or both (n = 337) possessed the mosaic penA XXXIV allele (cefixime: 87%, 276/317, P < 0.001; ceftriaxone: 61%, 59/96, P < 0.001). SNP analysis revealed that there were two major clades containing ESCem isolates that appear to have arisen independently. Notably, Clade A (MLST ST1580; 2009–2011) contained 30, primarily CFXem isolates, while the largest clade in the study (Clade B, MLST ST1901; 2006–2017) contained 224 ESCem isolates. A third clade (Clade C, MLST ST1600; 2014–2017) contained 6 ESCem isolates with a novel penA LXXI.

Conclusion The prevalence of mosaic penA XXXIV alleles was highest among gonococcal isolates with reduced susceptibility to ESCs over a 12-year period. Genomic methods can aid in efforts to monitor antimicrobial resistance markers of concern and ultimately slow the emergence and spread of circulating ESCem strains.

Disclosure No significant relationships.

  • Neisseria gonorrhoeae

https://doi.org/10.1136/sextrans-2019-sti.123

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