Background Since June 2022, there has been a rise in the number of ceftriaxone resistant Neisseria gonorrhoeae cases detected in England (n = 15), of which one third were extensively-drug resistant (XDR). We describe the demographic and clinical details of the recent cases and investigate the phenotypic and molecular characteristics of the isolates. For a comprehensive overview, we also reviewed 16 ceftriaxone-resistant cases previously identified in England since December 2015 and performed a global genomic comparison of all publicly available ceftriaxone-resistant N. gonorrhoeae strains with mosaic penA alleles. Methods All N. gonorrhoeae isolates resistant to ceftriaxone (MIC >0.125 mg/L) were whole-genome sequenced and compared with 142 global sequences of ceftriaxone-resistant N. gonorrhoeae. Demographic, behavioural, and clinical data were collected, including treatment and outcomes. Results All cases were heterosexuals, and most infections were associated with travel to or from the Asia-Pacific region. However, some had not travelled outside England within the previous few months. There were no ceftriaxone genital treatment failures, but 3/5 pharyngeal infections and the only rectal infection failed treatment. The isolates represented 13 different multi-locus sequence types (MLSTs), and most had the mosaic penA-60.001 allele. The global genomes clustered into eight major phylogroups, with regional associations. All XDR isolates belonged to the same phylogroup, represented by MLST 16406. Conclusion Ceftriaxone resistance in N. gonorrhoeae continues to be associated with the penA-60.001 allele within multiple genetic backgrounds and with widespread dissemination in the Asia-Pacific region. Heightened surveillance activities have been initiated to detect further cases with the aim of interrupting further transmission.

The authors have declared no competing interest.

This study was funded by UKHSA

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The Research Ethics and Governance Group of the UK Health Security Agency waived ethical approval for this work. This analysis was undertaken for health protection purposes under permissions granted to UKHSA to collect and process confidential patient data under Regulation 3 of The Health Service (Control of Patient Information) Regulations 2020 and Section 251 of the National Health Service Act 2006.

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