A looming penicillin shortage threatens pregnant adults with syphilis and their newborns

Pfizer announced last week that it expects to run out of a key drug for treating syphilis in the near future — a looming problem that health professionals say could exacerbate syphilis rates, widen racial disparities in sexually transmitted diseases, and stymie global access to the antibiotic, especially within lower-income countries.

The drug in question is Bicillin, an injectable, long-acting form of penicillin most commonly used to treat syphilis in adults as well as childhood infections. In a letter to customers last week, Pfizer estimated that the supply for kids may run out as early as the end of the month, while supply for adults could deplete in September.

For the most part, there are alternative antibiotics that doctors can use to treat childhood infections and syphilis in adults. But Bicillin is the only treatment safe enough for pregnant adults with syphilis, said Erin Fox, associate chief pharmacy officer at the University of Utah Health and an expert in tracking drug shortages.

“For pregnant adults, this really is the drug of choice,” Fox said. “Even if you have a penicillin allergy, they will work to desensitize you to that penicillin so that you can receive treatment.”

Without access to Bicillin, pregnant adults with syphilis and their newborns could face severe consequences.

“We’re dealing with babies that could be born with birth defects, or die even before they’re born,” said Chase Cannon, acting assistant professor in the division of allergy and infectious diseases at the University of Washington.

Cases of syphilis reached a record low in the U.S. at the turn of the 21st century, but have increased steadily over the past two decades. That surge culminated in a nearly 30% increase in U.S. cases between 2020 and 2021, according to the Centers for Disease Control and Prevention. More than 175,000 people in the U.S. contracted syphilis in 2021, with close to 54,000 cases of the most infectious stages of the disease reported.

One factor behind the uptick in cases, according to Cannon, may be the potential mixing of “sexual networks or social networks that didn’t used to mix.” While the disease had historically been most prevalent in men who have sex with men, it is now more frequently being detected in cisgender women as well as men who have sex with women, he said.

All this means that increased demand for Bicillin has contributed to the impending shortage. Additionally, the capacity to make more Bicillin is limited by supply-chain disruptions, the fact that Pfizer is the only manufacturer of the antibiotic, and that manufacturing requires dedicated factory space to avoid contamination with other drugs.

“It’s complicated to make and it’s a small market,” said Fox. “So I think it makes perfect sense why there might not be other companies also making this product.”

Meg Doherty, director of the Global HIV, Hepatitis, and STI Programmes at the World Health Organization, said that the organization has been concerned about shortages of penicillin, including its active manufacturing ingredients, for a while.

“We saw 39 countries around the world from 2014 to 2016 with shortages due to related changes in manufacturers that caused temporary derailments in the drug market,” said Doherty. “It’s not surprising that we are starting to see shortages again with increasing rises in syphilis.”

Doherty said that WHO estimates that 6 million doses of Bicillin are needed to treat adult syphilis in low- and middle-income countries.

While Fox doesn’t anticipate any dramatic increases in Bicillin pricing as a result of the shortage, she said she could anticipate “new entrants” that come to market at permanently higher prices in light of the current deficit.

By prescribing alternative antibiotics where possible, physicians can try to safeguard the remaining Bicillin supply to prioritize pregnant patients with syphilis. But alternative treatments bring their own set of challenges.

Doxycycline, another antibiotic, is a common alternative to Bicillin. However, unlike Bicillin’s long-acting formulation, which often only requires a single dose, doxycycline must be taken twice a day for two weeks. This extended treatment course could reduce patient compliance and leave syphilis infections unresolved, thus allowing patients to continue transmitting the disease to other people and prolonging the congenital syphilis outbreak, said Cannon. Additionally, excessive dependence on doxycycline, both to prevent and cure infections, could cause a secondary shortage, he said.

Nadia Sam-Agudu, a pediatrician who works in Nigeria, said that the drug shortage may also pose a problem for HIV transmission control.

“Treatment of syphilis actually reduces HIV transmission among sexual partners, and treating syphilis in pregnant women also prevents transmission of the disease to the baby,” said Sam-Agudu, who is part of the Institute of Human Virology at the University of Maryland School of Medicine. Having syphilis hinders the body’s ability to fight HIV and limits responsiveness to HIV treatments.

While drug supply issues are not uncommon, both Sam-Agudu and Doherty said the Bicillin shortage is an acute health equity concern for lower-income countries. “It’ll worsen health inequalities around treatments for pregnant women, increase deaths related to congenital syphilis and transmissions,” said Doherty. The WHO is working to strengthen local procurement efforts and demand forecasting for antibiotic drugs.

To avoid the dire outcomes of such shortages, Marta Wosińska, an economist at the Brookings Institution, recommends establishing stock reserves of drugs that lack alternatives, are difficult to manufacture, and prevent severe adverse health outcomes.

“We really need to be thinking about buffering our supply chains and having that cushion so that if there is a shock, we can recover from that shock,” Wosińska said. In her new policy proposal to address persistent generic drug shortages, Wosińska suggests forming both federally funded and hospital-wide “buffer inventories” to reduce the risk of treatment delays or resorting to subpar alternatives.

Pfizer’s Bicillin supply is not expected to recover until next year. Until then, many public health and medical providers will have to exercise their creativity and resourcefulness to minimize impact to patients. “It is incumbent on [physicians] to really look at their practice and say, how can we preserve the stock for the greater good?” said Cannon. “Because there are people who really need Bicillin, and we should try to save it for those cases.”