What NOT to Use for Syphilis? Azithromycin Resistance Skyrockets

July 24, 2024

Written by Clay Smith

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Treponema pallidum, the bacteria that cause syphilis, has nearly universal (99.2%) resistance to azithromycin. Use penicillin in these patients.

At least we know what NOT to use
Syphilis cases are on the rise. This infection remains sensitive to penicillin, but some patients may have a penicillin allergy. Can we use a macrolide instead? The short answer is – no. In the early 2000s, resistance to macrolides was noted among T. pallidum strains. From 2017-2023, samples from 13 U.S. states showed a high prevalence of macrolide resistance (99.2%, 599/604). This was due to mutation of the ribosomal RNA, and resistance remained even in the presence of antibiotic doses up to 64 times the minimum inhibitory concentration. Thankfully, penicillin G remains effective, and long-acting benzathine penicillin is the treatment of choice for syphilis. If benzathine penicillin is unavailable or the patient is allergic, the authors recommend using ceftriaxone or doxycycline instead, assuming they are not pregnant.

How will this change my practice?
I can’t recall ever reaching for azithromycin to treat syphilis, but I certainly won’t now. Penicillin remains the drug of choice. This is a situation in which a reported penicillin allergy should be thoroughly investigated to determine if it is true. We’ve covered using PEN-FAST to do a direct oral challenge (PALACE RCT) in order to safely de-label some pen-allergic patients. If ever there was a role for de-labeling, this is it.

Source
Near-Universal Resistance to Macrolides of Treponema pallidum in North America. N Engl J Med. 2024 Jun 13;390(22):2127-2128. doi: 10.1056/NEJMc2314441. PMID: 38865666