Comment on Callado et al: “Syphilis Treatment: Systematic Review and Meta-analysis Investigating Nonpenicillin Therapeutic Strategies”

In an era of steadily increasing rates of syphilis, dramatic rises in congenital syphilis, and intermittent scarcity of first line benzathine penicillin G (BPG), providers and health jurisdictions are more frequently turning to alternative treatment options.The authors conducted a systematic review and meta-analysis to summarize evidence from clinical trials and cohort studies through August 2023 comparing three non-penicillin antibiotics with BPG for the treatment of syphilis. 1he meta-analysis includes 5 studies that evaluated azithromycin as monotherapy for syphilis, all of which took place between 1995-2014.They conclude that ceftriaxone, azithromycin, and doxycycline are equivalent to BPG in terms of serologic cure rates for syphilis.Though serologic cure is one important outcome, it is not the only clinical factor that providers consider when developing a syphilis treatment plan.We agree with the rationale that convenient dosing for patients is important, especially as numbers of cases have increased in persons with unstable housing or who use substances for whom serial follow-up for weekly BPG injections is a major challenge.Yet, there is a critical oversight in the conclusions as presentedmacrolide resistance in Treponema pallidum subsp pallidum (T.pallidum) is incredibly high. 2 As a result of increasing macrolide use for other conditions driving emergent resistance, azithromycin has not