When researcher Vita Jongen, PhD, from the Department of Infectious Diseases at the Public Health Service Amsterdam in Amsterdam, Netherlands, set out to understand the informal public use of the antibiotic doxycycline for syphilis prevention, she was surprised by what she found.

Not only were many people obtaining the antibiotic without a prescription, but she and colleagues were surprised at the number using it as daily preexposure prophylaxis (PrEP) and that many were turning to other antibiotics to prevent sexually transmitted infections (STIs).

“We found that most people got doxycycline abroad. In some European countries you can get it over the counter cheaply,” Jongen told Medscape News Europe.

The research points to a widening tension playing out in Europe. As syphilis rates climb to their highest levels in over a decade, doxycycline postexposure prophylaxis (doxyPEP) has become one of the few new tools shown to reduce infections. But there is no EU-wide consensus on who should use it. National guidelines range from cautious to nearly silent, and uncertainty remains over its long-term effect on antimicrobial resistance (AMR). While regulators and clinicians weigh those questions, many of those most at risk aren’t waiting for an answer; they’re sourcing the antibiotic themselves. That raises a harder question of what happens when public health guidance lags behind the behavior of the people it’s meant to protect.

The excitement around doxyPEP stems from an unusually strong evidence base for a sexual health intervention. The first data came from a substudy of the French ANRS IPERGAY trial, which gave a single dose of doxycycline to men on HIV PrEP within 24 hours of condomless sex, and found a 47% relative reduction in bacterial STIs overall, with reductions of 70% for chlamydia and 73% for syphilis. That was followed by the DoxyPEP trial, a US-based open-label randomized study among men who have sex with men (MSM) and transgender women on PrEP or living with HIV, which tracked STI incidence and AMR over a year of follow-up. Combined, the major trials showed that a one-time 200-mg dose of doxycycline, taken within 72 hours of an unprotected encounter, could cut transmission of syphilis, gonorrhea, and chlamydia by roughly two thirds in high-risk populations.

A Patchwork of Guidance

This is important because bacterial STIs are on the rise across Europe. In May this year, the European Centre for Disease Prevention and Control (ECDC) reported that, in 2024, syphilis and congenital syphilis had reached their highest levels in over a decade. Between 2015 and 2024, syphilis cases more than doubled to 45,577, whereas congenital syphilis nearly doubled between 2023 and 2024. The sharp increase has been driven by “widening gaps in testing and prevention,” the ECDC said. While MSM remain the most disproportionately affected group, there is also a concerning rise in cases among women of reproductive age.

In January this year, the ECDC released public health considerations on the use of doxyPEP for the prevention of bacterial STIs, namely syphilis, but also gonorrhea and chlamydia. The guidance advises that use be decided at an individual level based on a clinician’s assessment of infection risk. If implemented, it says, the focus should be on preventing syphilis, “targeted specifically at groups at the highest risk of infection rather than the broader population.” The primary concern, it added, is the potential for doxyPEP to accelerate AMR.

At the national level, most professional European societies have converged on a similar case-by-case approach. The German STI Society advises against broad use, recommending it only case by case. The Spanish Association of Infectious Diseases and Clinical Microbiology has stated it’s not approved for STI prevention but recommends individualized prescriptions among MSM or transgender women with a history of recurrent STIs, following shared decision-making with patients. France, which has carried out several landmark trials on its efficacy, including IPERGAY and DOXYVAC, allows it case by case through sexual health clinics following a personal risk evaluation.

Jean-Michel Molina, MD, PhD, professor of infectious diseases at the University of Paris and head of the Infectious Diseases Department at the Saint-Louis and Lariboisière Hospitals in Paris, France, who was lead author on both French trials, told Medscape News Europe that doxyPEP’s implementation for STI prevention has been limited due to a lack of support for its rollout.

“In France we are experiencing a continuous increase in incidence of syphilis in men and women,” he said. “I am indeed using doxyPEP with my patients. I use it mostly among MSM patients on PrEP or those living with HIV with a history of recent STIs. Patients hear about it from friends and ask to use it.”

What’s become clear is that doxyPEP is now a valuable — and popular — tool for many across Europe.

Balancing Access and Resistance

John Gilmore, PhD, assistant professor at the School of Nursing, Midwifery and Health Systems at University College Dublin in Dublin, Ireland, has researched doxyPEP’s use in Ireland. His research among gay, bisexual, and other MSM found that more than one quarter of respondents used doxyPEP within the past year, and more than two thirds reported interest. Nearly half of those who had used it had accessed it informally, including online and from friends.

Since his research, Ireland has developed interim guidance for clinicians, with access managed on a case-by-case basis through STI clinics.

Rather than demonize people using doxyPEP informally, or place restrictions on those who want to use it, Gilmore would like to see more clinicians engaging with their patients to help them make an informed decision.

“We learnt from the HIV crisis that keeping scientific developments from communities most at risk is not a good idea. And we learnt from HIV PrEP that getting people to prove their risk isn’t the best way to engage them. Anyone who thinks they can stop doxyPEP’s use — or those who choose not to prescribe it — doesn’t mean its use will stop,” he told Medscape News Europe.

“By suggesting people are taking it willy nilly would be wrong. People are making informed decisions based on their risk profile. The community here in Ireland take the protection of themselves and their partners very seriously.”

On the widespread concerns about AMR, Gilmore said more research, surveillance, and monitoring is required.

“Right now, we have studies saying there’s no direct impact on AMR — it’s a hypothetical that doxyPEP may impact resistance, but we’re not seeing it. That doesn’t mean we just go full steam ahead. We need an informed approach to help support people to protect their health. It’s about balancing things,” he said.

“For me, AMR is a major issue, but there are numerous reasons why we have AMR and I’m not sure doxyPEP is a major one. It’s important for all clinicians who prescribe to exert AMR stewardship but that doesn’t mean an outright ban on antibiotics for people.”

Molina said that he and colleagues had monitored AMR extensively and that “so far the risks have been limited,” though he added that long-term monitoring is warranted.

Jongen’s research in the Netherlands among MSM, transgender, and gender-diverse people found that 15% had used doxyPEP/PrEP informally in the 6 months prior to the survey, and 22.5% had ever used it. While the Netherlands recently updated its position statement on doxyPEP to give clinicians a little more room to discuss it with patients at sexual health centers, Jongen said she expected informal use to continue to grow.

For now, she’d like to see more education around syphilis.

“Most likely we will need a combination of different prevention strategies to tackle the increasing incidence, such as condoms, education, test and treat, partner notification, and doxyPEP,” Jongen said.

Gilmore stressed that having another tool in the toolbox to tackle STIs is nothing but positive.

“Having an armory of as many interventions as possible to help with STIs is very positive,” he said. “We don’t need to be paternalistic about it. We need to look at in a mature way.”

Jongen, Molina, and Gilmore reported no relevant financial relationships.

Sophie Cousins, MIPH, is a global health journalist who has reported from more than 20 countries.