The Enhanced Gonococcal Surveillance Programme, Cambodia

Antimicrobial resistance in Neisseria gonorrhoeae is a global public health threat, exemplified by increasing reports of isolates with high minimum inhibitory concentrations (MICs) to cephalosporin antibiotics, the last remaining first-line agent.1Unemo M Lahra MM Escher M et al.WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017–18: a retrospective observational study.Lancet Microbe. 2021; 2: e627-e636Summary Full Text Full Text PDF PubMed Scopus (55) Google Scholar Since 2015, there have been sporadic reports of N gonorrhoeae isolates with elevated ceftriaxone MIC values from several countries. The overwhelming majority of these isolates harbour the penA-60.001 allele (a gene encoding the gonococcal penicillin binding protein 2, associated with ceftriaxone resistance) and are closely related to the original described resistant strain, FC428.2European Centre for Disease Prevention and ControlExtensively drug-resistant (XDR) Neisseria gonorrhoeae in the United Kingdom and Australia – 7 May, 2018. ECDC, Stockholm2018Google Scholar, 3Day M Pitt R Mody N et al.Detection of 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae in the United Kingdom, December 2021 to June 2022.Euro Surveill. 2022; 272200803Crossref Scopus (9) Google Scholar An increase in the detection of such isolates from returned travellers was reported in the UK and Austria.3Day M Pitt R Mody N et al.Detection of 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae in the United Kingdom, December 2021 to June 2022.Euro Surveill. 2022; 272200803Crossref Scopus (9) Google Scholar, 4Pleininger S Indra S Golparian D et al.Extensively drug resistant (XDR) Neisseria gonorrhoeae causing possible treatment failure with ceftriaxone plus azithromycin in Austria, April 2022.Euro Surveill. 2022; 272200455Crossref PubMed Scopus (18) Google Scholar The Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) uses standardised methods for antimicrobial resistance surveillance5WHOEnhanced Gonococcal Surveillance Programme.https://www.who.int/publications/i/item/9789240021341Date accessed: January 25, 2023Google Scholar and was established in Cambodia in 2020. In 2021–22, N gonorrhoeae was isolated from 93 urethral specimens collected from symptomatic males in Cambodia where the clinical guidelines recommend a single oral 400 mg dose of cefixime. The N gonorrhoeae isolates were referred to the partnering WHO collaborating centre in Australia for confirmation and genomic analysis (see appendix pp 7–8). 76 (82%) of these 93 specimens were viable after transport. Ceftriaxone MIC values 0·125mg/L or greater were detected in 38% of isolates (29 [38%] of 76). All 29 isolates were also resistant to penicillin, ciprofloxacin, and cefixime, and harboured the penA-60.001 allele across 9 different multi-locus sequence types on genomic analysis. Moreover, three (4%) of 76 isolates met the criteria for the extensive drug resistant phenotype with high level azithromycin co-resistance (MIC ≥256 mgL) and all were ST-16406 as previously reported.4Pleininger S Indra S Golparian D et al.Extensively drug resistant (XDR) Neisseria gonorrhoeae causing possible treatment failure with ceftriaxone plus azithromycin in Austria, April 2022.Euro Surveill. 2022; 272200455Crossref PubMed Scopus (18) Google Scholar Placing these within the global context of all previously reported penA-60.001 strains revealed that few Cambodian isolates clustered with the FC428 strain (figure). Two clusters exclusively contained Cambodian isolates, suggesting previously unrecognised emergence events across multiple new genomic backbones. These cluster however, were interspersed by other sequences originating from other countries in the region. This indicates that penA-60.001 carriage within N gonorrhoeae is more extensive than previously reported in the global literature, signifying that widespread dissemination across the region might have already occurred. Genomic analysis of the Cambodia EGASP N gonorrhoeae isolates identified a further 29 new emergent penA-60.001-associated resistant isolates from a single setting, including three extensive drug resistant isolates that are of significant concern. Given the N gonorrhoeae antimicrobial resistance surveillance gaps in Asia-Pacific, if this pattern and proportion of resistant genotypes is indicative of the situation elsewhere, the future role of cephalosporins as first-line therapy is questioned. This report confirms the urgent need for ongoing and expanded enhanced culture-based antimicrobial resistance surveillance and shows the usefulness of genomic sequencing to enhance our understanding of antimicrobial resistance evolution and spread. Moreover, these results highlight the need for urgent actions and strategies, including next antimicrobial recommendations and development of new preventative and therapeutic agents. EGASP Cambodia working group Say Heng Lon, Phal Kun Mom, Serongkea Deng, Virak Mok (National Center for HIV/AIDS, Dermatology and Sexually Transmitted Diseases, Phnom Penh, Cambodia), Rebekah M Frankson, Kristen Kreisel, Robert McDonald (Division of STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA), Martina Escher, Ismael Maatouk (Global HIV, Hepatitis and STI Programmes, WHO, Geneva Switzerland), Ratan L Kundu, Sanghamitra Ray, Jasmin El Nasser, Tiffany R Hogan (WHO Collaborating Centre for Sexually Transmitted Infections and Antimicrobial Resistance, New South Wales Health Pathology, Microbiology, The Prince of Wales Hospital Randwick, NSW, Australia), David M Whiley (Faculty of Medicine, University of Queensland, Brisbane, Australia) We declare no competing interests. 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