Abstract
The increasing transmission and antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global health concern with worrying trends of decreasing susceptibility to also the last-line extended-spectrum cephalosporin (ESC) ceftriaxone. A dramatic increase of reported gonorrhea cases has been observed in Sweden from 2016 and onward. The aim of the present study was to comprehensively investigate the genomic epidemiology of all cultured N. gonorrhoeae isolates in Sweden during 2016, in conjunction with phenotypic AMR and clinical and epidemiological data of patients. In total, 1279 isolates were examined. Etest and whole-genome sequencing (WGS) were performed, and epidemiological data obtained from the Public Health Agency of Sweden. Overall, 51.1%, 1.7%, and 1.3% resistance to ciprofloxacin, cefixime, and azithromycin, respectively, was found. No isolates were resistant to ceftriaxone, however, 9.3% of isolates showed a decreased susceptibility to ceftriaxone and 10.5% to cefixime. In total, 44 penA alleles were found of which six were mosaic (n = 92). Using the typing schemes of MLST, NG-MAST, and NG-STAR; 133, 422, and 280 sequence types, respectively, and 93 NG-STAR clonal complexes were found. The phylogenomic analysis revealed two main lineages (A and B) with lineage A divided into two main sublineages (A1 and A2). Resistance and decreased susceptibility to ESCs and azithromycin and associated AMR determinants, such as mosaic penA and mosaic mtrD, were predominantly found in sublineage A2. Resistance to cefixime and azithromycin was more prevalent among heterosexuals and MSM, respectively, and both were predominantly spread through domestic transmission. Continuous surveillance of the spread and evolution of N. gonorrhoeae, including phenotypic AMR testing and WGS, is essential for enhanced knowledge regarding the dynamic evolution of N. gonorrhoeae and gonorrhea epidemiology.
Highlights
Neisseria gonorrhoeae, the causative agent of gonorrhea, is a global public health concern with increasing transmission and development of antimicrobial resistance (AMR) (Rowley et al, 2019; Unemo et al, 2021)
Minimum inhibitory concentrations (MICs; mg/L) of ceftriaxone, cefixime, ciprofloxacin and spectinomycin were interpreted according to the clinical breakpoints recommended by the European Committee on Antimicrobial Susceptibility Testing
50.3% of patients were reported as men who have sex with men (MSM)
Summary
The causative agent of gonorrhea, is a global public health concern with increasing transmission and development of antimicrobial resistance (AMR) (Rowley et al, 2019; Unemo et al, 2021). The resistance to the extended-spectrum cephalosporins (ESCs) in the EU/EEA has decreased since 2009, as observed in the surveillance performed in the European Gonococcal Antimicrobial Susceptibility Programme, which is funded by the European Centre for Disease Prevention and Control (Cole et al, 2015; Cole et al, 2019; European Centre for Disease Prevention and Control [ECDC], 2021; Jacobsson et al, 2021) This trend may have been partly caused by the changed treatment implemented through the 2012 European gonorrhea guideline, in which cefixime 400 mg was replaced by ceftriaxone 500 mg plus azithromycin 2 g dual therapy as the recommended empirical first-line treatment for uncomplicated gonorrhea (Bignell and Unemo, 2013). The first gonococcal strain with ceftriaxone resistance combined with high-level resistance to azithromycin was detected in the United Kingdom and Australia in 2018 (Jennison et al, 2019) and the ceftriaxone-resistant strain FC428, including its sublineages, has been transmitted internationally since 2015 (Golparian et al, 2018; Lahra et al, 2018; Lee et al, 2019; Chen et al, 2020)
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