Ceftriaxone resistance in Neisseria gonorrhoeae associated with the penA-60.001 allele in Hanoi, Viet Nam
Authors: Paul C Adamson, Vu N Hieu, Pham H Nhung, DM Whiley, TM Chau
Journal: The Lancet Infectious Diseases (2024)

Antimicrobial resistance in Neisseria gonorrhoeae is an urgent global health threat. Ceftriaxone is the only remaining option for empirical monotherapy of gonococcal infections. The prevalence of ceftriaxone resistance in N gonorrhoeae is highest in the Western Pacific region.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 Google Scholar Many of the N gonorrhoeae infections associated with high minimum inhibitory concentrations (MICs) to ceftriaxone reported in the USA, the UK, and the rest of Europe carry the penA-60.001 allele, which is associated with ceftriaxone resistance and was first detected in the Western Pacific region.2Reimche JL Pham CD Joseph SJ et al.Novel strain of multidrug non-susceptible Neisseria gonorrhoeae in the USA.Lancet Infect Dis. 2024; 24: e149-e151Summary Full Text Full Text PDF Google 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 (25) Google Scholar, 6Maubaret C Caméléna F Mrimèche M et al.Two cases of extensively drug-resistant (XDR) Neisseria gonorrhoeae infection combining ceftriaxone-resistance and high-level azithromycin resistance, France, November 2022 and May 2023.Eurosurveillance. 2023; 282300456Crossref Scopus (4) Google Scholar The Enhanced Gonococcal Surveillance Programme in Cambodia recently reported 29 (38%) of 76 urethral isolates collected from 2021–22 were associated with ceftriaxone MICs of 0·125 mg/L or more.4Ouk V Pham CD Wi T van Hal SJ Lahra MM The Enhanced Gonococcal Surveillance Programme, Cambodia.Lancet Infect Dis. 2023; 23: e332-e333Summary Full Text Full Text PDF PubMed Google Scholar Moreover, all of those resistant isolates harbored the penA-60.001 allele. These findings are alarming and raise questions over whether ceftriaxone resistance and penA-60.001 are more widespread in the region. From January through to December, 2023, all isolates at the Hanoi Medical University Hospital (Hanoi, Viet Nam) were selected for antibiotic susceptibility testing (figure). MICs were interpreted through European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. All isolates with ceftriaxone MICs of 0·125 mg/L or more underwent DNA extraction and subsequent penA-60.001 detection by real-time PCR, based on a penA-60.001 PCR previously used for enhanced surveillance in other settings.2Reimche JL Pham CD Joseph SJ et al.Novel strain of multidrug non-susceptible Neisseria gonorrhoeae in the USA.Lancet Infect Dis. 2024; 24: e149-e151Summary Full Text Full Text PDF Google Scholar, 5Whiley DM Mhango L Jennison AV Nimmo G Lahra MM Direct detection of penA gene associated with ceftriaxone-resistant Neisseria gonorrhoeae FC428 strain by using PCR.Emerg Infect Dis. 2018; 24: 1573-1575Crossref PubMed Scopus (20) Google Scholar In total, 243 N gonorrhoeae isolates were cultured and 13 (5%) of these were non-viable. Of the 230 available isolates, 224 (97%) were obtained from urethral specimens. Ceftriaxone MICs greater than 0·125 mg/L were found in 64 (28%) of the 230 isolates and MICs greater than 0·25 mg/L were detected in 50 (22%) isolates. The penA-60.001 positivity was 67% (n=39/64) among those with MICs greater than 0·125 mg/L and 62% (n=31/50) among isolates with MICs greater than 0·25 mg/L. All (n=64/64) isolates with ceftriaxone MICs greater than 0·125 mg/L were resistant to cefixime, with MICs of 0·5 mg/L or more, and were susceptible to azithromycin (EUCAST epidemiological cutoff ≤1 mg/L). These findings highlight the troublingly high prevalence of ceftriaxone resistance in the Western Pacific region, with more than a quarter of N gonorrhoeae isolates resistant to first-line therapy in this setting, and that strains harboring penA-60.001 are becoming increasingly prevalent in many settings in the Western Pacific region. Our report underscores the utility of direct detection of penA-60.001, which could be used to rapidly detect resistance and might prove to be a useful surveillance tool more widely. The findings also suggest the presence of non-penA-60.001 mutations contributing to ceftriaxone resistance in this setting. Further analyses with whole-genome sequencing and multilocus sequence typing would help to elucidate those resistance mutations and better understand their transmission dynamics. Ceftriaxone as first-line therapy for gonorrhea is under threat and interventions are urgently needed to improve the detection of resistance and to mitigate further transmission. DMW reports research funding from SpeeDx, outside the submitted work. All other authors declare no competing interests. This work was supported by the National Institutes of Health, Fogarty International Center (K01TW012170 to PCA). The funder had no role in the data collection, analysis, or interpretation, or the decision to submit to publication.