One Dose of penicillin Shows Promise as Effective Syphilis Treatment
A recent late-stage clinical trial suggests a single injection of benzathine penicillin G (BPG) is as effective in treating early-stage syphilis as the current standard of three injections. This finding arrives at a critical time, as the United States has experienced recurring shortages of BPG, marketed as Bicillin L-A, impacting access to treatment.
Syphilis is a bacterial infection spread through direct contact with infected lesions. Untreated, it can lead to severe health complications, including damage to the brain, heart, and nervous system. The infection poses a particularly grave risk to newborns, causing a condition called congenital syphilis, which can result in miscarriage, stillbirth, or lifelong health problems for the infant.
Rates of both syphilis and congenital syphilis have been climbing in recent years. In 2023, over 209,000 cases of syphilis were reported in the U.S., a 61% increase since 2019. Congenital syphilis cases rose even more dramatically, with 3,882 reported in 2023 – a 108% increase from 2019.
The National Institutes of Health (NIH)-funded study involved 249 participants diagnosed with syphilis. Participants were randomly assigned to receive either a single intramuscular BPG injection or the standard three-dose regimen, administered one week apart. Six months post-treatment, researchers analyzed blood samples and found a 76% success rate in the single-dose group, compared to 70% in the three-dose group. This difference was not statistically significant.
The current three-dose regimen requires multiple healthcare visits, which can be a barrier to completion for some patients. A single-dose treatment could significantly improve access and adherence. “Benzathine penicillin G is highly effective against syphilis, but the three-dose regimen can be burdensome and deter people from attending follow-up visits with their healthcare providers,” stated Dr. Carolyn Deal, chief of the NIH’s enteric and sexually transmitted infections branch. “The new findings offer welcome evidence for perhaps simplifying treatment with an equally effective one-dose regimen…”
BPG availability has been hampered by frequent shortages over the past two decades, including a nearly five-year disruption. Just as supply began to recover from a two-year shortage in July 2025,Pfizer recalled certain lots due to potential contamination. The U.S. is currently relying on imports to address the national shortage.
While further research is warranted, a shift to a single-dose BPG treatment could substantially improve the availability and accessibility of this vital medication.
