Sustained transmission of the ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone in China

Background: Ceftriaxone resistance in Neisseria gonorrhoeae has become an imminent threat to effective control of gonorrhoea globally. In recent years, the ceftriaxone-resistant FC428 clone has shown international dissemination. After our first report of the FC428 clone in China in 2016, we now describe another six cases of FC428-related ceftriaxone-resistant N. gonorrhoeae isolates from 2017 and 2018. Objectives: To identify the phenotypic and molecular characteristics of newly reported ceftriaxone-resistant isolates in China and to investigate the relationship between these isolates and FC428 clones reported globally. Methods: Antimicrobial susceptibility to ceftriaxone, cefixime, azithromycin, spectinomycin, penicillin, ciprofloxacin and tetracycline was determined by the agar dilution method. N. gonorrhoeae multi-antigen sequence typing (NG-MAST), MLST and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were performed for genotyping and SNPs extracted from whole-genome sequences were used for phylogenetic analysis. Results: All isolates were resistant to ceftriaxone, cefixime, penicillin, tetracycline and ciprofloxacin, but were susceptible to azithromycin and spectinomycin. NG-MAST, MLST and NG-STAR genotyping showed that all isolates shared identical or similar STs (<10 bp difference) to FC428 (NG-MAST ST3435, MLST ST1903, NG-STAR ST233) and contained the same mosaic penA allele 60.001. Phylogenetic analysis showed the Chinese isolates spreading in the whole phylogenetic tree and fully mixed with other international isolates. Half of the Chinese isolates were more closely related (<100 SNPs) to Japanese isolates than other international isolates. Conclusions: The newly reported cases in China were related to the internationally spreading FC428 clone. These isolates might have played a central role in international transmission of the FC428 clone. High ceftriaxone doses (1-2 g) still provide effective therapy.