Antimicrobial susceptibility patterns of Neisseria gonorrhoeae across anatomical sites within and between individuals in the Netherlands: a retrospective observational study.

Abstract

Pharyngeal gonococcal infections are likely to contribute to the development of antimicrobial resistance (AMR) because of suboptimal efficacy of antibiotics in the pharynx, gene transfer with commensal Neisseria species, and the asymptomatic nature of pharyngeal infections. However, not all studies have found higher levels of AMR in pharyngeal than in anogenital sites. We studied antimicrobial susceptibility patterns across anatomical sites, both between and within individuals. This retrospective observational study used data from sexual health centres in the Netherlands participating in the Gonococcal Resistance to Antimicrobials Surveillance (GRAS) programme and included consultations of men who have sex with men (MSM) and women from Jan 1, 2016, to Dec 31, 2023. We included MSM and women with valid antimicrobial susceptibility results reported for at least one anatomical site. Susceptibilities to ceftriaxone and azithromycin were measured using minimum inhibitory concentration (MIC) values at the laboratories affiliated with the individual sexual health centres. The primary outcomes were increased ceftriaxone MICs, azithromycin resistance, and site-specific geometric mean MICs. We calculated anatomical site-specific proportions for increased ceftriaxone MICs (MIC>0·032 mg/L) and azithromycin resistance (MIC>1 mg/L) and geometric mean MICs (gmMICs) for both antibiotics. Differences between anatomical sites were analysed in the total GRAS population and within individuals for whom MICs were measured from multiple anatomical sites at the same clinic visit. Within the latter group, we describe within-individual discordant MIC pairs (defined as a difference of more than one MIC doubling dilution), and factors associated with discordance were analysed using logistic regression. In the study period, 16 916 consultations in MSM and 2521 consultations in women with at least one MIC available were included. The proportions of increased ceftriaxone MIC and azithromycin resistance and gmMICs for both antibiotics were highest in pharyngeal isolates in both groups. Among 1217 MSM and 457 women with multi-site MICs, proportions of increased ceftriaxone MIC, azithromycin resistance, and gmMICs were similar across anatomical sites. Discordant MIC pairs were observed in 117 of 1217 consultations in MSM (9·6%, 95% CI 8·1-11·2) and 22 of 457 consultations in women (4·8%, 3·1-6·7) for ceftriaxone, and in 147 of 1210 consultations in MSM (12·1%, 10·4-14·0) and 42 of 456 of consultations in women (9·2%, 6·8-11·8) for azithromycin. Within these discordant MIC pairs, pharyngeal MICs were similar to urogenital and anal MIC values. No sexual behavioural characteristics were significantly associated with discordant MICs. These findings suggest that higher resistance levels observed at the population level may reflect between-person variation rather than consistent within-person anatomical-site differences. Approximately 10% of individuals showed within-person MIC discordance, potentially leading to missed AMR cases if only one site is sampled. This finding suggests that culturing specimens from multiple anatomical sites could improve AMR detection, surveillance accuracy, and treatment decision-making. Further studies are needed to clarify the role of different anatomical sites in the transmission and development of gonococcal AMR. The Dutch Ministry of Health, Welfare and Sport.