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Even after all these years, a single dose of intramuscular penicillin G remains the preferred treatment for early-stage syphilis. The usual alternative, oral doxycycline, is problematic because several weeks of treatment are needed, and poor patient adherence can compromise efficacy.
In a multinational randomized nonblinded trial, 517 nonpregnant, HIV-negative adults with primary, secondary, or early latent syphilis received benzathine penicillin G (2.4 million units administered in 2 intramuscular injections) or azithromycin (2 g, administered as four 500-mg tablets). After 6 months, about 75% of patients in each group were judged as cured by the usual serologic standard of a drop in rapid plasma reagin (RPR) titer of ≥2 dilutions. Four pat…