Macrolide Resistance in Treponema pallidum in the United States and Ireland

Abstract

For decades, syphilis infection has been treated with penicillin , and Treponema pallidum has not developed resistance to penicillin. In many coun- tries, the recommended treatment for early syphilis is a single dose of penicillin G benzathine, which maintains bactericidal levels for weeks, killing the slowly metabo- lizing treponemes. Azithromycin, which has a long tissue half-life and can be admin- istered orally, was found to be effective in the treatment of syphilis in a rabbit model 1 and in small studies in humans. 2-6 Because of its convenience and efficacy, azithromycin is increasingly being used for the treatment of syphilis by clinicians and in disease-con- trol activities in Canada and the United States, although it is not currently recommend- ed by the Centers for Disease Control and Prevention. 7 We discuss one patient with clinical failure of azithromycin therapy for syphilis, among several cases that have been recognized. 8 We identified a mutation in the 23S ri- bosomal RNA (rRNA) genes in a specimen of T. pallidum obtained from this patient, and we confirmed functional azithromycin resistance in vivo in a strain of T. pallidum that contain this mutation. Testing of T. pallidum samples obtained at four geographi- cally diverse sites revealed a high frequency of this mutation in clinical specimens.