High tetracycline and azithromycin resistance of Neisseria gonorrhoeae impacting treatment and doxyPEP use - antimicrobial susceptibility patterns of isolates from a prospective cohort of men who have sex with men in Wroclaw, Lower Silesia, Poland 2022–2024 – final report

The aim was to ascertain Neisseria gonorrhoeae (NG) antimicrobial resistance patterns among men who have sex with men (MSM), evaluate their impact on treatment and prophylaxis, identify risk factors for infection, and assess whether expanding the sample size beyond the preliminary cohort significantly altered the primary outcomes (1). This trial was conducted at the outpatient All Saints’ HIV clinic in Wroclaw, Poland, between 2022 and 2024. Rectal, urethral, and oropharyngeal swabs were collected from 200 MSM who were wither living with HIV (PLWH) or using pre-exposure prophylaxis (PrEP). Included participants reported high-risk sexual contacts, symptoms, or prior positive results. NG isolates were evaluated for susceptibility to ceftriaxone, cefixime, azithromycin, ciprofloxacin, tetracycline, and benzylpenicillin. Of the 200 MSM enrolled, 33.5% were PLWH and 66.5% were PrEP users. This extended analysis identified 23 additional isolates alongside the initial 26, yielding 43 viable isolates for susceptibility testing. PrEP users were slightly younger than PLWH (median 34 vs. 36 years) and reported more oral contacts, more sexual partners outside of Poland, and more partners of foreign nationality within Poland. Doxycycline post-exposure prophylaxis (doxyPEP) was more frequently utilized by PLWH (30.3% vs. 14.18%). NG culture positivity rates were similar between PLWH (21.7%) and PrEP users (23.3%). In multivariate logistic regression, NG infection was significantly associated with higher number of oral contacts (OR = 4.05; 95% CI: 1.15–14.27; p = 0.029). While all isolates retained full susceptibility to ceftriaxone and cefixime, resistance to azithromycin was 30.2% (13/43) and tetracycline 48.8% (21/43), demonstrating stability between the preliminary and final analyses. Ceftriaxone and cefixime remain highly effective first-line agents against NG in Poland, whereas high resistance rates dictate that azithromycin should be relegated to alternative therapy status in national guidelines. Furthermore, the high prevalence of tetracycline resistance may compromise the efficacy of doxyPEP. Finally, the initial cohort of 100 MSM was statistically sufficient to accurately ascertain core antimicrobial resistance patterns. Not applicable. In recent years, gonorrhoea incidence rates among MSM have continued to increase, substantially exceeding those observed in the general population. Neisseria gonorrhoea (NG) has developed resistance to nearly all antimicrobial classes used for treatment and is classified as a high-priority pathogen by the World Health Organisation. Despite this global threat, there is currently minimal to no structured monitoring of NG antimicrobial resistance (AMR) patterns among key populations in Poland and several other European countries. This study demonstrates a complete absence of resistance to ceftriaxone and cefixime, contrasted with alarmingly high rates of resistance to both azithromycin and tetracycline among local NG isolates. To our knowledge, this is the first prospective report on NG resistance patterns among MSM in Poland, providing crucial contemporary data on AMR and its immediate implications for treatment guidelines and biomedical prophylaxis. Bacterial culture and susceptibility testing must remain an integral component of routine diagnostic workflows to monitor evolving resistance patterns. High susceptibility (low minimum inhibitory concentrations [MICs]) supports the continued use of highly effective ceftriaxone monotherapy. Conversely, national guidelines recommending ceftriaxone plus azithromycin combination therapy should be revised, relegating azithromycin to an alternative treatment status.