NEW YORK (Reuters Health) – A single dose of azithromycin cured early syphilis as effectively as the standard painful penicillin injections, in a recent phase III trial.

But it’s not time yet to use this finding in “the real world” – and even when it is, the researchers caution, azithromycin should not be given to pregnant women, it might not be safe for HIV-coinfected patients, and there is “lingering concern” regarding the potential impact of macrolide resistance in Treponema pallidum.

Benzathine penicillin G has been the standard of care for early syphilis for more than 60 years, the investigators noted in an April 28 online report in the Journal of Infectious Diseases.

For “the first randomized controlled trial conducted under US Food and Drug Administration oversight to evaluate a new therapy for syphilis,” Dr. Edward Hook III from the University of Alabama, Birmingham and colleagues enrolled 517 subjects age 18-55 years with primary, secondary, or early latent syphilis who were not pregnant and not infected with HIV.

They assigned 255 patients to treatment with oral azithromycin (four 500-mg tablets taken at once under direct observation) and 262 to receive two IM injections of 1.2 million units of benzathine penicillin G.

In the intent-to-treat analysis, the serological cure rate at 6 months (the primary end point) was 77.6% in the azithromycin group and 78.5% in the penicillin group — indicating, the authors say, that azithromycin is noninferior to penicillin.

Azithromycin was also noninferior in the per-protocol analysis, with similar cure rates.

No one in either group had persistent or recurrent clinical manifestations of syphilis.

There were no serious adverse events related to the study drugs. Non-serious side effects (gastrointestinal, central nervous system, cutaneous, and administration-related) occurred in 174 patients in the azithromycin group and in 132 in the penicillin group; the imbalance was related primarily to increased GI side effects with azithromycin.

The authors note that the 23S rRNA mutation for macrolide resistance in Treponema pallidum is spreading, but how much this contributes to treatment failure in syphilis patients given azithromycin is unknown.

The researchers also emphasize that congenital syphilis occurs despite treatment with macrolides, and so pregnant women “should definitely not be treated with azithromycin for their infections.”

“The adoption of azithromycin for routine syphilis therapy will require translational research studies and monitoring of azithromycin resistance,” Dr. Hook and associates conclude.

Reference:

J Infect Dis 2010.