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Purpose <p>Emergence of ceftriaxone-resistant <i>Neisseria gonorrhoeae</i> strains expressing <i>penA</i> allele 60.001 poses a major threat to the efficacy of ceftriaxone-based therapies. This study in Hangzhou, China, investigated the molecular epidemiology and antimicrobial susceptibility of 479 <i>N. gonorrhoeae</i> isolates collected from 2019 to 2025 to track the evolution of this resistance.</p> Methods <p>Antimicrobial susceptibility of <i>N. gonorrhoeae</i> isolates was determined by agar dilution method. Sequence types were identified by multi-locus sequence typing (MLST). Whole-genome sequencing and phylogenetic analysis were performed on high-level ceftriaxone-resistant isolates.</p> Results <p>While overall ceftriaxone resistance fluctuated, a significant and alarming resurgence of high-level resistance (MIC ≥ 0.5&#xa0;mg/L) was observed in 2024 (35%) and 2025 (19%), which was primarily driven by the expansion of strains harboring <i>penA</i> allele 60.001. Genetic characterization revealed a critical epidemiological shift: whereas early <i>penA</i> allele 60.001 isolates (2019–2021) were linked to the internationally disseminated FC428 clone (MLST ST1903), subsequent years witnessed the complete displacement of this clone by successful endemic lineages. From 2022 onwards, the resistant isolates belonged predominantly to ST8123 and, to a lesser extent, ST7365. Whole-genome sequencing and core-genome phylogenetic analysis confirmed that ST8123 forms a genetically distinct clade from ST1903, demonstrating that local, highly prevalent strains have acquired <i>penA</i> allele 60.001 and are now responsible for propagating this critical resistance determinant.</p> Conclusion <p>The rapid clonal expansion of ceftriaxone-resistant endemic lineages in China underscores an urgent need for enhanced global surveillance and a re-evaluation of current empirical therapy guidelines to mitigate the impending threat of untreatable gonorrhea.</p>

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Rapid expansion of penA allele 60.001-containing endemic ceftriaxone-resistant gonococcal ST8123 lineage in Hangzhou, China

  • 期刊论文

  • 发表日期：

    2026年7月10日

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  • Xia Sun,
  • Ying Fu,
  • Feng Zhao,
  • Xu’ai Lin,
  • Yan Chen,
  • Stijn van der Veen

摘要

Purpose

Emergence of ceftriaxone-resistant Neisseria gonorrhoeae strains expressing penA allele 60.001 poses a major threat to the efficacy of ceftriaxone-based therapies. This study in Hangzhou, China, investigated the molecular epidemiology and antimicrobial susceptibility of 479 N. gonorrhoeae isolates collected from 2019 to 2025 to track the evolution of this resistance.

Methods

Antimicrobial susceptibility of N. gonorrhoeae isolates was determined by agar dilution method. Sequence types were identified by multi-locus sequence typing (MLST). Whole-genome sequencing and phylogenetic analysis were performed on high-level ceftriaxone-resistant isolates.

Results

While overall ceftriaxone resistance fluctuated, a significant and alarming resurgence of high-level resistance (MIC ≥ 0.5 mg/L) was observed in 2024 (35%) and 2025 (19%), which was primarily driven by the expansion of strains harboring penA allele 60.001. Genetic characterization revealed a critical epidemiological shift: whereas early penA allele 60.001 isolates (2019–2021) were linked to the internationally disseminated FC428 clone (MLST ST1903), subsequent years witnessed the complete displacement of this clone by successful endemic lineages. From 2022 onwards, the resistant isolates belonged predominantly to ST8123 and, to a lesser extent, ST7365. Whole-genome sequencing and core-genome phylogenetic analysis confirmed that ST8123 forms a genetically distinct clade from ST1903, demonstrating that local, highly prevalent strains have acquired penA allele 60.001 and are now responsible for propagating this critical resistance determinant.

Conclusion

The rapid clonal expansion of ceftriaxone-resistant endemic lineages in China underscores an urgent need for enhanced global surveillance and a re-evaluation of current empirical therapy guidelines to mitigate the impending threat of untreatable gonorrhea.