{"doi":"10.1093/cid/ciaf530","title":"<i>PenA</i> Alleles Associated With Gonococcal Ceftriaxone Resistance in Cambodia, China, and Vietnam","abstract":"BACKGROUND: The global dissemination of ceftriaxone-resistant Neisseria gonorrhoeae, primarily associated with mosaic penA alleles, threatens the efficacy of ceftriaxone therapy. While the FC428 clone and its associated penA allele 60.001 are well-documented, data on other emerging resistance-conferring alleles in high-burden regions remain limited. This study characterizes the penA alleles associated with ceftriaxone resistance in Cambodia, China, and Vietnam. METHODS: Publicly available and novel genomes of N. gonorrhoeae isolates from Cambodia, China, and Vietnam with decreased ceftriaxone susceptibility (minimum inhibitory concentration [MIC] ≥ 0.125 mg/L) were analyzed. Multi-locus sequence types and penA alleles were assigned using PubMLST and BIGSdb and a core-genome neighbor-joining phylogenetic tree was constructed. To address selection bias, all isolates with reduced susceptibility from Hangzhou, China (2015-2022), were also analyzed for penA alleles using the NG-STAR method. RESULTS: Analysis of 236 genomes revealed that ceftriaxone resistance (MIC > 0.125 mg/L) was predominantly associated with penA alleles 60.001 (n = 145) and 237.001 (n = 70), which formed 2 major phylogenetic clades. All resistance-conferring alleles contained the A311 V polymorphism. PenA 60.001 was linked to multiple sequence types (STs), including FC428-associated ST1903 and endemic STs like ST8123 and ST8130. PenA 237.001 was almost exclusively found in Vietnam, primarily in ST1901. Analysis of the unbiased Hangzhou dataset (n = 132) confirmed that high-level resistance (MIC = 0.5-1 mg/L) was exclusively linked to penA 60.001. CONCLUSIONS: Ceftriaxone resistance in the Asia Pacific region is primarily driven by penA 60.001 and 237.001 along with related alleles harboring the A311 V polymorphism. The concerning acquisition of these alleles by successful endemic lineages enhances their potential for local and international spread.","journal":"Clinical Infectious Diseases","year":2025,"id":527943,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":384654,"name":"Xia Sun","orcid":"0000-0001-7733-9502","position":1,"is_corresponding":false},{"id":1405947,"name":"Haoyu Ge","orcid":null,"position":2,"is_corresponding":false},{"id":1365665,"name":"Trần Minh Châu","orcid":null,"position":3,"is_corresponding":false},{"id":1364813,"name":"Hong Nhung Pham","orcid":"0000-0002-4543-8386","position":4,"is_corresponding":false},{"id":636839,"name":"Koen Vandelannoote","orcid":"0000-0001-8367-4083","position":5,"is_corresponding":false},{"id":1405948,"name":"Gauthier Delvallez","orcid":null,"position":6,"is_corresponding":false},{"id":1405949,"name":"Sokleaph Cheng","orcid":null,"position":7,"is_corresponding":false},{"id":1364812,"name":"Jolein Laumen","orcid":"0000-0003-0168-5622","position":8,"is_corresponding":false},{"id":1405950,"name":"Paul C Adamson","orcid":null,"position":9,"is_corresponding":false},{"id":1405946,"name":"Stijn Van der Veen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T02:50:44.062153Z","pmid":"41504563","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}