Over 50% of syphilis cases in San Francisco in 2004 involved infection with a strain of bacteria which was resistant to the antibiotic azithromycin, according to investigators writing in the February 1st edition of Clinical Infectious Diseases (now online). They recommend that use of the antibiotic for the treatment of syphilis should be discontinued and that “intramuscular injection with benzathine penicillin G” or oral doxycyline for penicillin-allergic patients should be used instead.
In 1998 only five cases of syphilis were identified in San Francisco and health authorities in the United States initiated a plan for the nationwide elimination of syphilis in 1999. However, in 2004 a total of 340 cases of primary or secondary syphilis, mainly in gay or bisexual men, were identified in San Francisco, which now has one of the highest syphilis rates of any US city.
The only officially recommended treatment for syphilis in the US is intramuscular injection with benzathine penicillin G. For individuals who are allergic to penicillin, oral doxycycline is an accepted alternative. Other antibiotics, including tetracycline, erythromycin, and ceftriaxone, have also been shown to be effective against syphilis .
Studies have also shown that azithromycin, a macrolide antibiotic, is effective against syphilis. Indeed, one study showed azithromycin was as effective as benzathine penicillin G injections as therapy for primary or secondary syphilis. As a result of these studies Vancouver in Canada, Los Angeles in the USA and the Rakai district of Uganda adopted azithromycin as standard therapy for early syphilis.
Because of the rapidly expanding syphilis epidemic, public health officials in San Francisco also endorsed the use of single-dose 1g of azithromycin for incubating syphilis in 1999 and single-dose 2g of azithromycin for primary and secondary syphilis in 2000.
However, the Street 14 strain of syphilis is naturally resistant to azithromycin and the study investigators became concerned about reports of azithromycin treatment failure. They therefore gathered information on the clinical and epidemiological characteristics of patients experiencing azithromycin failure.
Syphilis samples were obtained from patients attending the San Francisco City Clinic between 2000 and 2004. These were then subjected to molecular analysis to see if there was resistance to azithromycin. Patient notes were also reviewed to identify individuals who had experienced azithromycin treatment failure. Information was obtained on patients’ demographic backgrounds and sexual activities.
A total of 533 individuals were diagnosed with syphilis at the San Francisco City Clinic in the four years of the study. Samples were obtained from 154 patients for molecular analysis, and this was successful in 118 cases. A total of 46 samples were found to involve syphilis that was resistant to azithromycin, with the remaining 72 samples containing wild-type syphilis.
In addition, seven cases of azithromycin treatment failure were identified by the investigators.
The median age of individuals with azithromycin-resistant syphilis was 37 years, 70% were white, all were men, all reported having sex with other men and 28% were HIV-positive.
The prevalence of azithromycin-resistant syphilis increased from 4% in 2000 – 2002 to 41% in 2003 and to 56% in 2004.
There was no evidence that any particular sexual networks were associated with the transmission of azithromycin-resistant syphilis.
Because of their findings, the investigators recommended in 2003 that azithromycin should no longer be used for the treatment of primary or secondary syphilis and in 2004 recommended that the prophylactic use of the drug for people who had sexual contact with individuals with syphilis should discontinue.
Mitchell SJ et al. Azithromycin-resistant syphilis infection: San Francisco, California, 2000 – 2004. Clin Infect Dis 42 (online edition), 2006.