Syphilis, caused by the bacterium Treponema pallidum subsp. pallidum (TPA), re-emerged as a global health problem in the twenty-first century, with a drastic increase in syphilis diagnoses reported in the past 20 years. Injection with the long-acting benzathine penicillin G is the gold-standard treatment for syphilis, but the increased number of patients combined with a limited supply chain capacity led to a global benzathine penicillin shortage. Thus, alternative therapies and vaccine development are absolute priorities in the field and have been discussed in two studies published in The New England Journal of Medicine and The Journal of Infection Diseases, respectively.

The first article is a correspondence in which the authors evaluated the current prevalence of azithromycin resistance to assess whether this macrolide antibiotic (which current Centers for Disease Control and Prevention and Canadian guidelines suggest not to use) could be included in the discussion about alternative syphilis therapies in the context of benzathine penicillin shortage. A total of 604 TPA strains were sampled between 2017 and 2023 across 13 US states, Washington DC and two Canadian states, and azithromycin resistance was assessed through the presence of A2058G or A2059G mutations in the 23S ribosomal RNA subunit gene, which both confer resistance to azithromycin. Overall, 99.2% of sampled strains (599 of 604) were genotypically resistant to azithromycin, with 584 (97.5%) and 15 (2.5%) strains carrying the A2058G and the A2059G mutations, respectively. Azithromycin resistance also drastically increased (99.3%) in women and in men who have sex with women, who historically experienced low resistance (14%, according to data obtained between 2007 and 2009). Patients in this study were shown to be representative of patients with syphilis in North America. Overall, the authors concluded that these data do not support the use of azithromycin, and clinicians should consider alternative solutions (doxycycline or ceftriaxone) in non-pregnant patients in the context of benzathine penicillin G shortage.

梅毒，由梅毒螺旋体亚种细菌引起。梅毒(TPA) 在 21 世纪重新成为全球健康问题，过去 20 年报告的梅毒诊断急剧增加。注射长效苄星青霉素G是治疗梅毒的金标准，但患者数量的增加加上供应链能力有限导致全球苄星青霉素短缺。因此，替代疗法和疫苗开发是该领域的绝对优先事项，并已在《新英格兰医学杂志》和《感染性疾病杂志》分别发表的两项研究中进行了讨论。

第一篇文章是一封信函，其中作者评估了阿奇霉素耐药性的当前流行情况，以评估这种大环内酯类抗生素（目前的疾病控制与预防中心和加拿大指南建议不要使用）是否可以纳入有关梅毒替代疗法的讨论中在苄星青霉素短缺的情况下。 2017 年至 2023 年间，对美国 13 个州、华盛顿特区和加拿大两个州总共 604 个 TPA 菌株进行了采样，并通过 23S 核糖体 RNA 亚基基因中是否存在 A2058G 或 A2059G 突变来评估阿奇霉素耐药性，这两种突变均赋予对阿奇霉素的耐药性。阿奇霉素。总体而言，99.2% 的采样菌株（604 株中的 599 株）对阿奇霉素具有基因型耐药性，其中 584 株（97.5%）和 15 株（2.5%）菌株分别携带 A2058G 和 A2059G 突变。女性和与女性发生性关系的男性对阿奇霉素的耐药性也急剧增加（99.3%），而历史上这些人的耐药性较低（根据 2007 年至 2009 年获得的数据，为 14%）。该研究中的患者被证明是北美梅毒患者的代表。总体而言，作者得出的结论是，这些数据不支持使用阿奇霉素，临床医生应在苄星青霉素 G 短缺的情况下考虑对非妊娠患者使用替代解决方案（多西环素或头孢曲松）。