Researchers have discovered that a one-time injection of benzathine penicillin G (BPG) is as effective as a three-dose regimen for treating early syphilis, according to findings from a late-stage clinical trial. This suggests that the second and third doses in the standard BPG treatment may not offer additional health benefits.
The results were published in the New England Journal of Medicine.
New England Journal of Medicine"Benzathine penicillin G is extremely effective against syphilis, but a three-dose regimen can be inconvenient and discourage patients from completing follow-up visits," said Carolyn Deal, Ph.D., head of the enteric and sexually transmitted infections branch at NIH's National Institute of Allergy and Infectious Diseases (NIAID).
"The new findings provide promising evidence for potentially simplifying treatment with an equally effective one-dose regimen, particularly given the concerning rise in syphilis cases."
Syphilis is a widespread sexually transmitted infection caused by the bacterium Treponema pallidum. The United States reported 209,253 syphilis cases and 3,882 congenital syphilis cases in 2023, representing increases of 61% and 108% respectively compared to 2019.
Without treatment, syphilis can lead to neurological and organ damage, severe pregnancy complications, and congenital abnormalities. It also heightens a person's risk of acquiring or transmitting HIV.
BPG is one of the few antibiotics known to effectively treat syphilis, with global shortages being common. Currently, it is being imported to the United States to address a nationwide shortage.
The study was carried out at 10 U.S. sites and involved 249 participants with early syphilis, encompassing primary, secondary, and early latent stages; 61% of participants were HIV-positive, and 97% were male.
Participants were randomly assigned to receive either a single intramuscular (IM) injection of BPG at 2.4 million units (MU) or a three-dose series of BPG 2.4 MU at weekly intervals. All participants were monitored for safety, and the serologic response to therapy was assessed in their blood six months after treatment.
Around 76% of participants in the single-dose group showed a serologic response compared to 70% in the three-dose group. The difference was not statistically significant, even when participants were stratified by HIV status.
One participant developed signs of neurosyphilis three days after initiating BPG therapy and was excluded from the analysis. Three serious adverse events occurred but were unrelated to BPG.
"Although syphilis has been studied for over a century and BPG used for more than 50 years, we continue to gain insights on optimizing treatment," said Principal Investigator Edward W. Hook III, M.D., emeritus professor of medicine and epidemiology at the University of Alabama at Birmingham.
"We hope these promising results will be supplemented by advancements in syphilis prevention and diagnosis."
The study authors note that these trial results offer substantial evidence that single-dose BPG 2.4 MU is as effective as three doses for treating early syphilis. Additional research is needed to understand the full potential of this abbreviated treatment strategy, particularly for different stages of syphilis, including late-stage and latent infections.
The study was conducted through the Sexually Transmitted Infections Clinical Trials Group.