After its 2000 nadir, US incidence of primary and secondary syphilis began increasing (from 2.2 cases per 100,000 population in 2001 to 2.5 cases per 100,000 in 2003), mainly among men who have sex with men (MSM). In San Francisco, which now has the highest P&S syphilis rate among US metropolitan areas, the rate increased from a 1998 nadir of 5 cases to 320 cases in 2004.

San Francisco Department of Public Health officials began using azithromycin as an alternative prophylactic treatment for incubating syphilis in July 1999 and for treatment of P&S syphilis in April 2000. Following treatment failure reports in San Francisco, researchers in the current retrospective case-control study sought to determine the risk factors and clinical and epidemiologic characteristics of patients with azithromycin-resistant Treponema pallidum infection during January 2000-December 2004.

The authors reviewed city-wide case reports and conducted molecular screening of San Francisco City Clinic patients to identify those who either did not respond to azithromycin or who were infected with azithromycin-resistant T. pallidum.

Molecular analyses of 124 samples identified 46 azithromycin-resistant T. pallidum isolates (from confirmed case group) and 72 wild-type T. pallidum isolates (among control group). A review of records showed treatment had failed in six patients.

Researchers identified 52 case patients (one of whom had two episodes) and 72 control patients. All case patients were male and either gay or bisexual, and 31 percent (16) were HIV-infected. An investigation revealed no sexual network or demographic differences between cases and controls. Among case patients, seven had recently used azithromycin compared to just one control patient. At the San Francisco City Clinic, surveillance data showed azithromycin-resistant T. pallidum increased from 0 percent of cases observed in 2000 to 56 percent in 2004.

"Azithromycin-resistant T. pallidum is widespread in San Francisco," concluded authors. "We recommend against using azithromycin for the management of syphilis in communities where macrolide-resistant T. pallidum is present and recommend active surveillance for resistance in sites where azithromycin is used."

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