Although the recommended treatment for syphilis is penicillin, azithromycin has been used as an alternative. We discuss azithromycin-related treatment failures and resistance in Treponema pallidum, and propose ways to meet the resulting clinical and public health challenges.
Azithromycin treatment failures in syphilis were first noted in San Francisco in 2002 and result from an A→G mutation at position 2058 of the 23S rRNA gene of T. pallidum. This mutation confers resistance by precluding macrolide binding to the bacterial 50S ribosomal subunit, of which 23S rRNA is a structural component. Azithromycin resistance has also been identified in T. pallidum specimens from elsewhere in the United States, Ireland, and Canada, and the amount of resistant specimens has increased with time. Treatment with azithromycin or other macrolides appears to be a risk factor for presenting with a resistant T. pallidum strain.
Although T. pallidum remains sensitive to penicillin and certain other antibiotics, azithromycin resistance in T. pallidum has emerged and is increasing in the United States, Canada, and Ireland. This poses clinical and public health challenges, and indicates a need for further antibiotic drug development and surveillance for resistance in T. pallidum. If azithromycin is used to treat syphilis, clinicians and public health practitioners should remain vigilant for treatment failures.
aEpidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
bSTD Prevention and Control Services, San Francisco Department of Public Health, USA
cDepartment of Medicine, University of California San Francisco, San Francisco, California, USA
Correspondence to Jeffrey D. Klausner, MD, MPH, Director, STD Prevention and Control Services, 1360 Mission Street, Suite 401, San Francisco, CA 94103, USA Tel: +415 355 2000; fax: +415 554 9636; e-mail: Jeff.Klausner@sfdph.org