O04.2 Phylogenomic analysis reveals persistence of neisseria gonorrhoeae clades with reduced susceptibility to cephalosporins. (14th July 2019)

• Record Type: Journal Article
• Authors: Thomas, Jesse; Abrams-Mclean, A Jeanine; Seby, Sandra; Schmerer, Matthew; Pham, Cau; Hong, Jaeyoung; Cyr, Sancta St; Gernert, Kim; Raphael, Brian; Kersh, Ellen
• Is Part Of: Sexually transmitted infections. Volume 95(2019)Supplement 1
• Page Start: A45
• Page End: A45
• Publication Date: 2019-07-14
• Subjects: Neisseria gonorrhoeae; Sexually transmitted diseases -- Periodicals; HIV infections -- Periodicals; 616.951005
• DOI: 10.1136/sextrans-2019-sti.123
• Languages: English
• ISSNs: 1368-4973

Abstract

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) (ESC em ). 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 ESC em 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 (CFX em ; MIC ≥ 0.25 μg/mL), 96 isolates with elevated ceftriaxone MICs (CRO em ; 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 ESC em isolates that appear to have arisen independently. Notably, Clade A (MLST ST1580; 2009–2011) contained 30, primarily CFX em isolates, while the largest clade in the study (Clade B, MLST ST1901; 2006–2017) contained 224 ESC em isolates. A third clade (Clade C, MLST ST1600; 2014–2017) contained 6 ESC em 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 ESC em strains. Disclosure: No significant relationships.