Genomic trends and emerging antimicrobial resistance in Neisseria gonorrhoeae over two decades in Kenya.

We investigated the trends and antimicrobial resistance (AMR) of Neisseria gonorrhoeae (NG) in Kenya with whole-genome sequencing (WGS) of isolates collected in 2002-2009 (n = 108) and 2020-2022 (n = 110). Phenotypic AMR was confirmed by agar dilution. Predicted minimum inhibitory concentrations (MICs), multi-locus sequence typing (MLST), multi-antigen ST (NG-MAST), NG-STAR, and AMR genetic determinants were determined using WGS and detection of molecular markers. The WGS cgMLST typing used LIN codes. Resistance to penicillin, ciprofloxacin, and tetracycline was common throughout. In 2020-2022, azithromycin resistance (n = 2) and cephalosporin alert values (n = 5) were observed. Phylogenetic clusters were congruent with the LIN code lineage, though other typing schemes (MLST, NG-STAR, and NG-MAST) were not as consistent. There were major shifts over time in the lineages and genetic determinants. Circumcision and HIV status were associated with several AMR, housekeeping, metabolism, and iron acquisition genetic determinants. These findings highlight dynamic NG genomic trends, emerging macrolide resistance, and the value of WGS for surveillance. Behavioral and biological factors may contribute to AMR emergence and warrant further investigation.IMPORTANCEThis work highlights the significant value of using whole-genome sequencing to track the evolution and epidemiology of gonorrhea over 20 years: (i) we documented the emergence of azithromycin resistance and cephalosporin reduced susceptibility and relationship to genetics of gonorrhea; (ii) by combining epidemiological and genetic data, we found that circumcision and HIV status were linked to specific genetic features of gonorrhea, including those tied to antibiotic resistance; and (iii) we used novel and traditional genetic typing methods to expand and refine the understanding of lineage shifts and genetic determinants, enhancing surveillance and intervention efforts. Some isolates had potential decreasing susceptibility for cephalosporins, highlighting the critical importance of ongoing surveillance and the opportunity for novel resistance gene identification. Studying how gonorrhea strains relate to a person's immune system, other bacteria (microbiome), and sexual networks could help us understand how certain strains spread and what the potential factors amplifying antimicrobial resistance are.