CHICAGO — Azithromycin-resistant strains of Treponema pallidum continue to emerge in San Francisco, despite the cessation of the drug's use for syphilis treatment and prophylaxis and for the treatment of nongonococcal urethritis in gay men.
The city's historically low 5% resistance rate jumped dramatically to 40% in 2003, just a year after the San Francisco Department of Public Health began using the drug prophylactically in the sex partners of gay men with symptomatic syphilis, Dr. Kenneth Katz said a conference on STD prevention sponsored by the Centers for Disease Control and Prevention. During this time, azithromycin also was used to treat both syphilis and nongonococcal urethritis in gay men who were allergic to penicillin. But despite a 2004 decision to stop using the drug for any syphilis treatment, resistance has risen linearly each year, to a high of 77% in 2006, Dr. Katz said at the meeting.
“This finding emphasizes a real need for vigilance in finding treatment failures in patients receiving azithromycin, and a need for surveillance of azithromycin-resistant syphilis in areas where this drug may be used to treat syphilis,” he said.
To this end, the CDC recently has launched a nationwide surveillance program to identify azithromycin-resistant T. pallidum strains, said Dr. Katz, a public health official with the CDC and the San Francisco Department of Public Health.
In 1998, gay men made up only 20% of the syphilis cases in San Francisco. By early 2002, that proportion had risen to 90%, Dr. Katz said. The dramatic increase spurred the city's health department to launch an aggressive program aimed at decreasing the spread of the disease. “Part of our response was to treat the sex partners of symptomatic patients with a single 1-g dose of azithromycin. Symptomatic patients who were allergic to penicillin were treated with a single 2-g dose.”
The protocol began in July 2002. “Shortly thereafter, we began to notice treatment failures in patients with primary or incubating syphilis who had been treated with azithromycin,” Dr. Katz said. Azithromycin kills microbes by binding at the ribosome to inhibit protein synthesis. Some strains of T. pallidum had developed a mutation that inhibited this ribosomal binding.
In September 2004, the city's health department ceased using azithromycin for any syphilis treatment. But a case-control study showed that the resistant mutation was associated with any azithromycin use within 30 days prior to the syphilis diagnosis. Therefore, Dr. Katz said, the ban on azithromycin was extended; in 2005, the health department discontinued its use in nongonococcal urethritis in gay men.
Despite these precautions, azithromycin resistance has continued to increase in San Francisco, he said. The department conducted a polymerase chain reaction assay on samples from 39 positive lesions in 2005 and 2006. Almost all of the cases (36) were among gay men. Of the 17 lesions sampled in 2005, 13 (76%) contained the resistant strain. Of the 22 samples examined in 2006, 17 (77%) contained the strain.
Azithromycin-resistant T. pallidum also has been found in Seattle and Baltimore, as well as some cities in Canada and Ireland, Dr. Katz noted.
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