Oral Presentation 25th International Pathogenic Neisseria Conference 2026

Azithromycin and ESC resistance are near mutually exclusive in global multi-drug resistant gonococci. (140614)

Anastasia F Unitt 1 , Angus A.M Quinn 2 , Odile B Harrison 1
  1. University of Oxford, Oxford, OXFORDSHIRE, United Kingdom
  2. Life Sciences, Warwick University, Coventry, United Kingdom

Multi-drug resistance (MDR) in Neisseria gonorrhoeae has been associated with treatment failures in recent years (Golparian et al., 2020). With widespread whole genome sequencing (WGS), we can now examine MDR in this genetically-flexible organism on an unprecedented scale. Here, we applied publicly available WGS and MIC data to explore patterns of MDR and their association with population structure.

Methods

Isolate data was accessed through PubMLST, a public database for the analysis of bacterial genomes (accessed 23/02/2026). We examined resistance to six antibiotics: penicillin, ciprofloxacin, azithromycin, tetracycline, ceftriaxone, and cefixime, across 26,866 genomes with associated MIC data. MDR was defined as resistance to three or more antibiotic classes (ceftriaxone and cefixime being of the same class, extended-spectrum cephalosporins [ESCs]). The incidence of resistance to each class was assessed statistically using a Binomial Generalised Linear Model (BGLM) and a Binomial Generalised Linear Mixed Model (BGLMM). Gonococcal lineages were characterised using LIN codes, a core genome-based strain typing system (Unitt et al., 2025).

Results

Within our dataset 5,277 isolates were classed as MDR (15%). Resistance to ciprofloxacin (5,085 isolates, 96%), tetracycline (5,243, 99%), and penicillin (4,880, 92%) was widespread across these isolates, while azithromycin (825, 16%) and ESC resistance (531, 10%) was less common. We detected a highly significant negative association between azithromycin and ESC resistance (Fisher’s Exact Test: OR = 0.29, p < 0.0001), with only 24 MDR isolates (0.45%) recorded as resistant to both antimicrobials. Lineage effects on this relationship were quantified through a BGLMM, which found that azithromycin and ESC resistance phenotype was stratified by LIN lineage (variance = 10.86, SD = 3.30, 129 lineages). I.e., distinct lineages were associated with resistance to either azithromycin or ESCs.

Summary

In conclusion, azithromycin resistance and ESC resistance arise in different genetic backgrounds in global gonococci, and rarely co-occur. Whether this is due to a fitness trade-off that selects against co-resistance to Azithromycin and ESCs remains to be seen. If so, the currently recommended 500 mg ceftriaxone monotherapy may inadvertently select for ESC-resistant lineages that would be suppressed under azithromycin–ceftriaxone dual therapy.

  1. GOLPARIAN, D., HARRIS, S. R., SÁNCHEZ-BUSÓ, L., HOFFMANN, S., SHAFER, W. M., BENTLEY, S. D., JENSEN, J. S. & UNEMO, M. 2020. Genomic evolution of Neisseria gonorrhoeae since the preantibiotic era (1928–2013): antimicrobial use/misuse selects for resistance and drives evolution. BMC Genomics, 21.
  2. UNITT, A., KRISNA, M. A., PARFITT, K. M., JOLLEY, K. A., MAIDEN, M. C. J. & HARRISON, O. B. 2025. Neisseria gonorrhoeae LIN codes provide a robust, multi-resolution lineage nomenclature. Elife, 14.