Syphilis is most often transmitted by sexual contact; symptoms of infection develop within 30 days in about one third of exposed persons. The long incubation period provides great opportunity for preventive therapy. Currently, intramuscular injection of penicillin G benzathine is recommended for preventive therapy in exposed persons. In persons allergic to penicillin, 14 days of treatment with doxycycline is the suggested alternative therapy, although this agent may be less effective than penicillin, especially in noncompliant persons. Azithromycin, an azalide antimicrobial agent, has been successfully used as a multidose treatment in persons who have early syphilis.

Hook and associates studied the effectiveness of a single, oral dose of 1 g of azithromycin for the prevention of syphilis in recently exposed persons. Patients known to have been exposed to syphilis were randomized to receive intramuscular injections of 2.4 million U of penicillin G benzathine or a single, oral dose of 1 g azithromycin. Patients were examined regularly for three months after therapy with rapid plasma reagin and fluorescent treponemal antibody-absorbed tests. Both therapeutic regimens were effective for syphilis prevention. None of the 63 participants who completed the study developed syphilis during the three-month follow-up period, compared with a previously reported 28 percent incidence among untreated patients with incubating syphilis.

The authors conclude that a single dose of azithromycin, currently recommended for the treatment of several other sexually transmitted diseases (e.g., Chlamydia, gonorrhea, nongonococcal urethritis and chancroid) is an acceptable single-dose alternative to the currently recommended alternative treatment with doxycycline twice daily for 14 days. The study also demonstrated a substantial patient preference for oral therapy. Because of the small number of study participants, further study of azithromycin for the treatment of syphilis is needed.