Drug Shortages, Increased Syphilis Cases Shift Focus to Prevention, Diagnosis, Treatment

Originally published by our sister publication Infectious Disease Special Edition

By Gina Shaw

With U.S. syphilis cases surging—they increased 80% between 2018 and 2022—a cross-governmental National Syphilis and Congenital Syphilis Syndemic Federal Task Force involving more than 200 members is focused on addressing the escalating epidemic in the face of drug shortages.

A Dec. 4, 2024 webinar featuring experts from the CDC, FDA, National Institutes of Health (NIH), and Department of Health and Human Services (HHS) highlighted treatment options in light of the ongoing penicillin shortage, point-of-care testing and new doxycycline post-exposure prophylaxis (doxy PEP) aimed at high-risk populations.

Between 2018 and 2022, reported cases of syphilis rose from 115,000 to more than 207,000. Penicillin, particularly benzathine penicillin G, remains the most effective treatment and is the first-line recommended therapy for all stages of syphilis in adults (and is especially crucial for reducing the risk for congenital syphilis). Pfizer’s Bicillin L-A is the only FDA-approved version of that drug on the U.S. market, and it has been on shortage since April 2023, as demand began to outpace supply.

“We have tried to mitigate the shortage by offering assistance to the manufacturer and others in the supply chain to reduce the impact of the reduced availability,” said Susan Bersoff-Matcha, MD, the deputy director of the Office of Women’s Health in the Office of the FDA Commissioner. “While the company was ramping up to produce their product at maximum capacity, FDA reached out to other international regulatory agencies.”

Although the agency found that most countries also identified Pfizer as their sole source, ultimately the FDA partnered with the French company Laboratoires Delbert to exercise regulatory authority and allow for the temporary importation of its product, benzathine benzylpenicillin (Extencilline), beginning in January 2024. In July, the FDA announced that it would also allow the temporary importation of a second drug, benzathine benzylpenicillin tetrahydrate (Lentocilin) from Portuguese manufacturer Laboratórios Atral.

“Meanwhile, supply of the FDA-approved Pfizer product is improving, and we've continued to work closely with the company to monitor inventory and production plans,” Dr. Bersoff-Matcha said.

In August, the FDA also authorized the first over-the-counter home test for syphilis, First to Know (Now Diagnostics), which provides results in about 15 minutes. “Patients may be calling you with the results of these tests,” Dr. Bersoff-Matcha said. “It’s important to know that the average time it takes to develop antibodies after exposure to syphilis is about 21 days, but it may be longer or shorter than that. So be mindful of the timing of exposure and the timing of testing. A negative or positive test does not preclude the possibility of infection with other pathogens or STIs [sexually transmitted infections], and it does not replace syphilis testing during pregnancy, but these tests do increase access and allow testing in private, and they increase awareness of STIs among the general population.”

In addition, there are two rapid point-of-care syphilis tests now available in the United States: the Syphilis Health Check Test (Diagnostics Direct) and the DPP HIV-Syphilis dual test (Chembio), noted Bradley Stoner, MD, PhD, the director of the Division of STD Prevention at the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention. “All three are treponemal tests, which generally remain positive after treatment for life in most patients, so they won’t help you that much if a patient has previously been treated for syphilis. So these point-of-care tests should ideally be used in settings where you might expect a higher incidence of new syphilis infections, such as correctional facilities, emergency departments in rural settings away from traditional STI clinics and other sexual health resources, shelters, and substance use treatment and harm reduction programs.”

There are no vaccines for the prevention of syphilis, but for high-risk populations, an effective prevention strategy can be the use of doxy PEP, a single, high dose of 200-mg doxycycline taken as soon as possible—within 72 hours—after oral, vaginal or anal sex. The CDC recommends that men who have sex with men and transgender women who have had a bacterial STI (specifically syphilis, chlamydia or gonorrhea) diagnosed in the past 12 months receive counseling that doxy PEP can be used as post-exposure prophylaxis to prevent these infections.

“At least three randomized trials have been conducted in populations of men who have sex with men and transgender women, who were either on HIV PrEP [pre-exposure prophylaxis] or living with HIV. All three demonstrated significant reductions in all three reportable STIs after doxy PEP,” Dr. Stoner said. “The number needed to treat in order to prevent a quarterly visit with an incident STI was 4.7 in the HIV PrEP cohort and 5.3 persons in the living with HIV cohort, so that means you don't have to treat that many people to prevent an infection.”