Background:
Azithromycin resistance in Treponema pallidum infections caused by an A2058G mutation in the 23s ribosomal RNA gene has been reported in the United States, Canada, and Ireland. In San Francisco (SF), the proportion of resistant T. pallidum infections was 1/24 (4.1%) during 1999–2002, 11/29 (37.9%) during 2003, and 37/68 (54.4%) during 2004. SF Department of Public Health (DPH) ceased using azithromycin to treat syphilis in 2004 and nongonococcal urethritis (NGU) among gay or other men who have sex with men (G/MSM) in 2005.

Objective:
To assess T. pallidum resistance in SF in 2005–2006 and factors associated with a resistant infection.

Method:
A2058G mutation assays were performed on specimens obtained from lesions among patients with primary or secondary syphilis examined at SF's municipal STD clinic during 2005–2006.

Result:
Forty-nine specimens were collected from 46 male patients and 1 male-to-female transgender patient. Two patients had repeat specimens collected, each during a distinct infection. Forty-four patients had primary syphilis. Thirty-seven specimens were from darkfield-positive lesions. Sufficient T. pallidum DNA was recovered from 39/49 samples (79.6%) analyzed to date. Of these 39, 13/17 (76.5%) in 2005 and 17/22 (77.3%) in 2006 yielded resistant T. pallidum. A total of 28/30 resistant infections (93.3%) and 8/9 nonresistant infections (88.9%) were among G/MSM. Ages of patients with resistant (median, 43.5 years; range 23–62) and nonresistant infection (median, 47 years; range 27–52) were comparable. A total of 13/30 resistant infections (43.3%) and 3/8 nonresistant infections (37.5%) were among HIV-infected patients.

Conclusion:
Azithromycin resistance in T. pallidum infections continued to increase in SF in 2005–2006, despite decreased azithromycin use for syphilis and NGU. Patients with resistant versus nonresistant infections did not significantly differ by select characteristics.

Implications:
Resistance in T. pallidum poses clinical and public health challenges, indicates a need for antibiotic development, and should prompt heightened clinical vigilance and laboratory surveillance.