The Obsolescence of Azithromycin for Syphilis Treatment and the Value of Contrasting Different Types of Evidence

We appreciate the comments by Cannon et al. regarding our article that compared non-penicillin antibiotics with benzathine penicillin for syphilis treatment.We conducted a systematic literature review and meta-analysis following rigorous scientific and methodological practices, adhering to standardized guidelines as described in our manuscript 1 .We aimed to summarize the current knowledge through the highest level of medical evidence, such as randomized controlled trials.Although the meta-analysis suggests a potential role for non-penicillin regimens, we emphasized that we fully agree with the CDC guidelines recommending penicillin as the first-line option for treating syphilis at any stage 2 .The search for alternative treatments for syphilis seeks to address situations where penicillin cannot be used, such as when there is a shortage of the antibiotic or when the patient is allergic.Our study presented evidence from randomized clinical trials indicating that azithromycin, doxycycline, and ceftriaxone may be equivalent to penicillin in achieving serologic cure rates after treatment.However, we appreciate Cannon and colleagues for expanding the discussion on why azithromycin should no longer be used as part of programmatic management guidelines despite the results of several published clinical trials.They rightfully point out that since the publication of the trials favoring azithromycin, epidemiologic data has shown a growing spread of azithromycin resistance worldwide.We acknowledge that we could have been more definitive in