At least 10 percent of syphilis samples from STD clinics in four cities in the United States and Ireland were resistant to azithromycin, according to a study published today. "That suggests that this mutation is pretty widely distributed geographically," said Sheila A. Lukehart, University of Washington-Seattle research professor of infectious diseases.

Among 114 samples from Seattle, San Francisco, Baltimore and Dublin, Ireland, 28 percent were azithromycin-resistant - but that figure includes resistant strains among 88 percent of Dublin samples. Drug-resistant San Francisco samples jumped from 4 percent in 1999-2002 to 37 percent in 2003, largely among gay or bisexual men with multiple partners.

CDC is formulating a plan to test for resistant syphilis strains in some areas, said Dr. John Douglas, director of the agency's division of STD prevention.

Doctors have been giving azithromycin to treat some syphilis patients since the 1990s because the antibiotic was highly effective and easy to use. Four pills taken at once were usually effective. Azithromycin was also an alternative to penicillin, which must be given in two painful injections in the buttocks.

Patients treated with azithromycin must have follow-up tests to be sure they are cured, said experts who recommend switching to penicillin or other antibiotics for syphilis if azithromycin does not work. However, some of these antibiotics must be taken for two weeks and can cause nausea or other side effects, which could cause treatment adherence problems or failure.

After declines through the 1990s, syphilis cases climbed 19 percent from 2000 to 2003, which CDC attributed to a 12-fold increase among gay and bisexual men, many of whom are coinfected with HIV.

The full report, "Macrolide Resistance in Treponema pallidum in the United States and Ireland," is published in today's New England Journal of Medicine (2004;351(2):154-158).