European health officials yesterday released guidelines on the preventive use of doxycycline to help curb a continent-wide surge in sexually transmitted infections (STIs).

The guidance issued by the European Centre for Disease Prevention and Control (ECDC) aims to support national public health authorities who are recommending use of doxycycline post-exposure prophylaxis (doxyPEP), which involves taking the antibiotic within 24 hours of unprotected sex, in high-risk individuals as part of a comprehensive sexual health strategy. 

It calls for good oversight of doxyPEP use in countries where it is implemented and monitoring of its public health impact, including the emergence of antimicrobial resistance (AMR).

The ECDC guidance, however, stops far short of a full-throated endorsement of doxyPEP and includes several caveats on its implementation.

“ECDC recommends that decisions regarding the use of doxy-PEP should be made at the individual level and follow clinical judgement and national guidelines,” agency officials said. “ECDC does not recommend a population-level intervention at this time.”

Recommendation focuses on syphilis prevention in high-risk groups

DoxyPEP has emerged as an STI prevention strategy based on clinical trial data showing that it is highly effective at reducing incidence of chlamydia and syphilis among men who have sex with men (MSM) and transgender women with a history of STIs. Those data have led the US Centers for Disease Control and Prevention and health officials in several other countries to recommend the intervention for those groups. 

DoxyPEP has also been shown to be similarly effective in real-world settings, particularly against syphilis and chlamydia. 

But ECDC officials say implementation should primarily be focused on prevention of syphilis infections, which have risen by 53% in European Union/European Economic Area (EU/EEA) countries since 2019. Chlamydia and gonorrhea infections have risen by 16% and 138%, respectively, over the same period.

That recommendation partly reflects what has been observed in clinical trials and real-world settings. In the doxyPEP trial conducted in San Francisco and Seattle, for example, preventive use of doxycycline by MSM and transgender women with a history of STIs reduced syphilis incidence by 87%, while chlamydia incidence fell by 88%. Gonorrhea incidence was reduced by only 55%. A trial conducted in France found similar results.

ECDC does not recommend a population-level intervention at this time.

The ECDC also recommends that the strategy, if implemented, be targeted at the groups at highest risk of infection, that decisions about the use of doxyPEP be based on a clinician’s assessment of a patient’s individual risk, and that users be informed of risks and benefits.

“In addition, doxy-PEP should not be a standalone measure and must be integrated into a comprehensive sexual health strategy that includes access to regular testing, vaccination, HIV prevention, and partner notification services,” ECDC officials said.

The guidance also notes that doxyPEP is unlikely to effectively reduce incidence of gonorrhea in Europe because of already-high levels of tetracycline resistance in circulating Neisseria gonorrhoeae strains. Although doxycycline hasn’t been used to treat gonorrhea since 1985, an ECDC report in October 2025 found that 58.4% of N gonorrhoeae isolates submitted by 24 EU/EEA member states in 2023 were tetracycline-resistant. 

More recent data published last week in Eurosurveillance show that the prevalence of tetracycline resistance has risen to 62.3%. And two recent studies, one in France and one in the United States, suggest that doxyPEP use may be promoting a rise in tetracycline-resistant gonorrhea. 

In addition, the guidance highlights the long-standing concern that doxyPEP could also promote the emergence and spread of mobile tetracycline resistance genes in “bystander bacteria” (eg, Staphylococcus aureus) that reside in the anatomical sites where STIs occur and in other parts of the body. That could potentially make treatment more difficult for bacterial infections that still rely on doxycycline and other tetracycline antibiotics—not only in high-risk doxyPEP users but in other populations.

“This poses a risk to both individual users and the wider community,” the ECDC said.

That concern has been voiced by public health officials, STI experts, and trial investigators, who’ve warned about the wider public health impact of increased tetracycline resistance and called for continued monitoring of AMR as doxyPEP becomes more widely adopted. It’s among the reasons why ECDC and other public health agencies have been limiting their recommendations to high-risk groups.

‘Ongoing uncertainty’ regarding risks, benefits

Monitoring who is using doxyPEP, and how it’s used, may prove difficult. A survey conducted by the ECDC in 2024 found that among more than 50,000 EU respondents—primarily MSM and gender-diverse individuals—8.2% reported using doxycycline or other antibiotics for STI prevention. 

And while some respondents said they had obtained their antibiotics through a prescription from a health care provider, others cited online sources, over-the-counter pharmacy purchases, and use of leftover medication from previous infections.

In another survey conducted in 2024 by researchers with the Public Health Service of Amsterdam, 22% of respondents reported using doxyPEP, even though it’s not recommended or actively promoted by Dutch health officials. 

The ECDC’s position appears to reflect the cautious approach that’s been taken by individual countries. German health officials, for example, recommend that preventive doxycycline “should be reserved for selected individuals in selected situations” and not be broadly implemented due to the “unclear effects of such a strategy on antimicrobial resistance.” The Belgian Research HIV Consortium recommends against widespread use of doxyPEP and encourages individual use to be done in a medically supervised setting.

The ECDC says these positions “reflect ongoing uncertainty regarding the public health benefits of this prophylactic intervention balanced with its potential harms, particularly the risk of increasing antimicrobial resistance.”