Austin (Vax-Before-Travel News)

The discussion about how long therapy with benzathine penicillin G (BPG) should last for individuals with early syphilis has recently been updated. Clinicians often use BPG to treat bacterial infections, such as syphilis, which is caused by T. pallidum. 

Researchers funded by the National Institutes of Health (NIH), reporting in the New England Journal of Medicine on September 3, 2025, found that a single injection of the antibiotic BPG was as effective as the three-injection regimen used in the treatment of early syphilis.

This topic is important because millions of people are affected by this sexually transmitted disease each year, and there are currently no approved syphilis vaccines available.

In this randomized, phase 4 clinical trial, 249 persons with early syphilis received a single treatment or three treatments with benzathine penicillin G at a dose of 2.4 million units. Most participants were men (97%), 62% were Black, and 61% were living with HIV infection.

The distribution according to syphilis stage was 19% with primary syphilis, 47% with secondary syphilis, and 33% with early latent syphilis.

The percentage of participants with a serologic response at 6 months was 76% (95% confidence interval [CI], 68 to 82) in the single-dose group and 70% (95% CI, 61 to 77) in the three-dose group (difference, −6 percentage points; 90% CI, −15 to 3, indicating noninferiority).

According to these researchers, no clinical relapse or treatment failure occurred in either group.

They concluded that the results from this trial provide substantial evidence that single-dose BPG 2.4 MU is as effective as three doses in treating early syphilis.

However, more research is needed to understand the full potential of this abbreviated treatment strategy and to evaluate therapeutic approaches for all stages of syphilis, including late syphilis, latent syphilis of unknown duration, and clinical neurosyphilis, stated these researchers in a related video.

As of September 7, 2025, the U.S. CDC publishes its syphilis treatment guidelines and disease overview.