Syphilis and azithromycin

Treating Syphilis Without Penicillin
A large study finds that a single oral dose of azithromycin can be curative in patients with early syphilis.

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 patients had clear treatment failure with a significant rise in RPR titers; all had received azithromycin. Adverse effects, primarily gastrointestinal, were more common in the azithromycin group.

Comment:

Single-dose azithromycin is an attractive treatment option for syphilis: It can be given under observation, is generally well tolerated, and can also be effective against chancroid, chlamydia, and gonorrhea. This study adds to the evidence that it works for syphilis, but concerns remain. Among them: efficacy in HIV infection, efficacy in pregnancy, and the observation that a mutation encoding for macrolide resistance is rapidly emerging in Treponema pallidum isolates.

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Abigail Zuger, MD
Published in Journal Watch General Medicine June 17, 2010

Citation(s): Hook EW III et al. A phase III equivalence trial of azithromycin versus benzathine penicillin for treatment of early syphilis. J Infect Dis 2010 Jun 1; 201:1729.