A dose of antibiotic treats early syphilis as well as three doses

Wednesday September 3, 2025

The clinical trial funded by NIH shows a potential to simplify the treatment of early syphilis.

Researchers financed by the National Institutes of Health (NIH) have found that one injection of the Penicillin G (BPG) antibiotic benzathine successfully treated early syphilis as well as the three injections used by many clinicians to the United States and elsewhere. These results of a clinical trial at an advanced stage suggest that the second and third doses of conventional BPG therapy do not provide health service. The results were published today in The New England Journal of Medicine.

“Benzathine penicillin is very effective against syphilis, but the three -doses regime can be heavy and dissuade people from attending follow -up visits with their health care providers,” said Carolyn Deal, PH.D., head of enterical diseases and sexually transmitted infections of the National Institute of Allergy and Infectious. “The new conclusions offer welcome evidence for potentially simplifying treatment with a dose at an equally effective dose, especially while syphilis rates remain alarming.”

Syphilis is a sexually transmitted current infection (IST) caused by the bacteria Pale treponema. The United States declared 209,253 cases of total syphilis and 3,882 cases of congenital syphilis in 2023, which represents 61% and 108% respectively compared to the figures of 2019. Without treatment, syphilis can cause neurological and organic damage as well as severe pregnancy complications and congenital anomalies. Syphilis can also increase a person’s probability of acquiring or transmitting HIV.

BPG is one of the rare antibiotics known to effectively treat syphilis, and stocks are common worldwide. The antibiotic is currently imported in the United States to resolve a national shortage.

The study was conducted in ten American sites and registered 249 participants in early syphilis, which includes the primary, secondary and early stages of the disease. Sixty-four percent of the participants lived with HIV and 97% were men. Participants were accidentally assigned to receive a single Intramuscular (IM) (IM) of BPG 2.4 million units (MU) or a series of three BPG injections of BPG 2.4 MU at weekly intervals. All participants were monitored for security. The biological markers of successful treatment in the blood – known as the serological response to treatment – were examined at six months after treatment.

Seventy-six percent of the participants of the single dose group had a serological response to treatment against 70% of three-dose group participants. The difference between the groups was not statistically significant, even when the participants were stratified by HIV status. A participant developed signs of neurosyphilis three days after the start of BPG treatment and was excluded from the analysis. Three serious adverse events were reported but were not linked to the BPG.

“Syphilis has been studied and treated for more than a century, and BPG has been used for over 50 years, but we have always acquired knowledge to help us optimize treatment,” said principal researcher Edward W. Hook III, MD, emeritus professor of medicine and epidemiology at the University of Alabama in Birmingham. “We hope that these promising results will be completed by scientific progress in the prevention and diagnosis of syphilis.”

According to study authors, the results of this test provide substantial evidence that the BPG at a single dose 2.4 MU is as effective as three doses in the treatment of early syphilis. Additional research is necessary to understand the full potential of this abridged treatment strategy and to assess therapeutic approaches for all stages of syphilis, including late syphilis, latent syphilis of unknown duration and clinical neurosyphilis.

The study was conducted by the clinical group of sexually transmitted infections funded by NIAID.

For more information on this trial, please visit Clinicals.gov using the identifier of the study NCT03637660.

Niaid conducts and supports research – in NIH, the United States and the world – to study the causes of infectious and immune mediation, and to develop better means of prevention, diagnosis and treatment of these diseases. Press releases, information sheets and other NIAID -related documents are available on the Niaid website.

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