INTRODUCTION: Neisseria gonorrhoeae (Ng) is the cause of the second most common bacterial sexually transmitted infection (STI) worldwide and a priority antimicrobial resistance (AMR) pathogen. It is widely accepted that pharyngeal infection plays an important role in the development and transmission of AMR and is a key site for control strategies. Ceftriaxone (CRO), alone or combined with azithromycin, is the current empirical treatment of choice in most regions. However, treatment failures (TFs) have already been reported in the literature, especially at pharyngeal infection sites. The main resistance mechanism to CRO is the development of penA mosaic genes acquired from commensal Neisseria (Nc) species during pharyngeal infection. Additionally, pharyngeal infection is more difficult to treat than other sites due to the pharmacokinetic limitations of many antimicrobials, leading to lower pharyngeal concentrations. This thesis aims to contribute to evidence relating to the surveillance of gonococcal and Nc AMR, the relationship between extended spectrum cephalosporin (ESC) TFs and minimum inhibitory concentrations (MICs), and the evaluation of novel treatment options relating to the pharyngeal site. METHODS: The work was carried out by a mixed methods approach; a systematic review was performed to summarise the relationship between treatment failures in pharyngeal and nonpharyngeal isolates. A cross-sectional study of 41 genitourinary clinic (GUM) patients was also undertaken to characterise gonococcal strains in multisite infection and estimate the proportion of patients carrying different strains between anatomical sites. Another cross-sectional study of 50 London School of Hygiene & Tropical Medicine (LSHTM) volunteers was employed to determine the pharyngeal carriage and AMR burden of Nc species. Lastly, the in vitro susceptibility of Ng and Nc strains to chlorhexidine (CHX), an antiseptic compound, were determined using laboratory methods. RESULTS: The systematic review identified that the pooled Ng MICs for pharyngeal TFs were lower than extra-pharyngeal TFs for both cefixime and ceftriaxone and lower than both the Clinical Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints for reduced susceptibility. Of the TFs for ceftriaxone, 66.7% (24/36) Pharyngeal gonorrhoea and AMR were in the pharynx, and 31% (11/36) had multisite infection that included pharyngeal infection but only failed treatment in the pharynx. Of 41 participants with multisite Ng infection, 14.6% (6/41; 95% [CI]; 6.88%, 28.4%) had different strains between anatomical sites, as determined by MICs. Molecular typing confirmed differing strains in four out of the six patients. Carriage rates of Nc species in our study participants were 86% (43/50; 95% [CI]; 73.8%, 93%) and AMR rates for cefixime and ceftriaxone were both higher than the reported Ng rates for that year. Lastly, clinical and control Ng strains showed high susceptibility to CHX. Additionally, CHX eradicated Ng strains within one minute. CONCLUSIONS: N. gonorrhoeae remains a critical priority in the fight against AMR, necessitating innovative public health strategies. This thesis proposes several key interventions: a) ongoing and improved monitoring and reporting of TFs with or without the review of AMR breakpoints for pharyngeal infection, b) enhanced antimicrobial susceptibility testing processes for multisite isolates, c) surveillance of the AMR burden in Nc species, and d) exploring treatments beyond traditional antimicrobials. Together, these approaches can support efforts to control the development and transmission of AMR in Ng.