<em>Neisseria gonorrhoeae</em> in the Era of Antimicrobial Resistance: From Curable STI to Clinical Challenge

Neisseria gonorrhoeae, the etiological agent of gonorrhea, has become a major global public health concern due to its remarkable ability to acquire antimicrobial resistance (AMR). Once curable with a wide range of antibiotics, the pathogen now demonstrates multidrug-resistant (MDR), extensively drug-resistant (XDR), and even pandrug-resistant (PDR) profiles, with rising reports of reduced susceptibility to ceftriaxone, the current last-line empirical therapy. Resistance to extended-spectrum cephalosporins, particularly ceftriaxone and cefixime, combined with azithromycin resistance, represents the most urgent threat to existing treatment regimens and raises the specter of untreatable gonorrhea in the absence of an effective vaccine. This review synthesizes current knowledge on the molecular basis of resistance, including efflux pump overexpression, target-site mutations, plasmid-mediated determinants, and horizontal gene transfer, which collectively contribute to the pathogen’s adaptability. It further integrates global epidemiological trends, surveillance data, and the public health consequences of emerging resistant lineages. Advances in rapid molecular diagnostics, novel antimicrobial and non-antimicrobial treatment strategies, and vaccine development efforts are critically examined. The review concludes by emphasizing the need for coordinated global surveillance, antimicrobial stewardship, and translational research pipelines to preserve therapeutic efficacy and accelerate the development of next-generation interventions against resistant N. gonorrhoeae.