- A Seattle clinic found 52% fewer syphilis cases after the rollout of doxycycline as prevention
- DoxyPEP involves taking the antibiotic doxycycline after sex to prevent some bacterial infections
- Despite decreases across all genders, diagnoses during pregnancy and among infants increased
Randomized controlled clinical trials in San Francisco and France have found a significant decrease in the risk of key sexually transmitted infections (STIs) when doxycycline post-exposure prophylaxis (doxyPEP) is used shortly after sex. In these well-designed studies, the risk of developing syphilis was reduced by 73 per cent to 80 per cent among gay and bisexual men who have sex with men (gbMSM) and transgender women who have sex with men. DoxyPEP decreased the risk of infection with chlamydia, and in places where the bacteria that cause gonorrhea were susceptible to this drug, the risk of gonorrhea also decreased.
The overall reduction in STI risk, demonstrated by these studies, has led to increasing doxyPEP use among gbMSM, transgender women and other populations at risk for key STIs.
Study in Seattle
Clinical trials are a highly controlled setting and may not always reflect conditions in the community. Therefore, researchers have been conducting observational studies in different parts of the world to assess the impact of doxyPEP.
A team of researchers in Seattle reviewed anonymized health-related information collected between May 2017 and June 2024 from people who attended a major sexual health clinic in the Seattle region (Seattle and King County Sexual Health Clinic). In particular, the researchers focused on people who were diagnosed with syphilis, some of whom were using doxyPEP. Between January 2017 and February 2023, doxyPEP was not routinely prescribed in Seattle for the prevention of STIs. However, beginning in March 2023, doxyPEP was prescribed, mainly to populations at high risk for STIs, including some gbMSM and transgender women.
Results
According to the researchers, “syphilis cases declined dramatically following implementation (March 2023) of doxyPEP [in the Seattle region].” As a result of the use of this antibiotic, overall there were 52 per cent fewer cases of syphilis (3,031 diagnoses). The decline of syphilis was distributed as follows:
- cisgender men – 53% fewer cases
- cisgender women – 47% fewer cases
- transgender and non-binary people – 33% fewer cases
Focus on pregnancy and infants
Rates of syphilis during pregnancy have been on the rise across North America during the past decade. Associated with this is an increase in infants born with syphilis (congenital syphilis).
According to the researchers, in the present study cases of syphilis diagnosed during pregnancy rose from 13 in 2017 to 48 in 2024. Cases of infants diagnosed with syphilis rose from none in 2017 to 23 in 2024.
The researchers stated that it appears there is limited overlap between “people who can become pregnant (or who desire pregnancy)” and sexual networks of people who use doxyPEP.
They also stated that “pregnant people with syphilis are more likely to experience poverty, houselessness, substance use, mental health challenges and [be involved with the criminal justice system]. Marginalized by the healthcare system, pregnant people with syphilis are less likely to receive adequate prenatal care and syphilis testing and treatment.”
However, all is not lost. The use of doxyPEP has resulted in a significant decrease in overall cases of syphilis—a tremendous achievement. This decrease in overall cases has allowed public health staff in the Seattle region to better focus on helping pregnant people with syphilis screening and treatment beginning in January 2025. The researchers stated that this focus on pregnant people may have helped reduce the marginalization associated with syphilis during pregnancy. In the first half of 2025, the researchers found a promising trend—fewer cases of infants born with syphilis than in the recent past. If this public health intervention can be sustained, rates of congenital syphilis may continue to fall.
Bear in mind
The present study was observational; it looked back on data collected for one purpose and reanalyzed the data for another purpose. This type of analysis can in theory lead to biased conclusions. However, the 52 per cent decrease in overall syphilis cases since 2023 in Seattle is very similar to a report from San Francisco since the implementation of doxyPEP, which observed an overall decrease of 51 per cent of syphilis cases.
The results after the implementation of doxyPEP in Seattle and San Francisco are promising, though more related research is needed. For instance, how often should doxyPEP be taken for optimal syphilis risk reduction? A single 200-mg dose of doxycycline taken orally results in high concentrations of the drug in the rectum, penis and vagina. These levels remain high against the germs that cause syphilis (four days), chlamydia (three days) and gonorrhea (two days). It is possible that people who use doxyPEP several times per month could have prolonged and high concentrations of doxycycline, theoretically leading to a greater degree of protection from syphilis. However, this requires additional studies.
The long-term impact of doxycycline use on the mix of bacteria that normally live in the gut needs monitoring. Also, further research is required to assess the potential risk of bacteria that cause STIs, particularly gonorrhea, developing reduced susceptibility to doxyPEP.
In reviewing the data from Seattle, physician Robert Bolan (University of Southern California School of Medicine) stated that “improving access to prenatal care and timely diagnosis and treatment of syphilis in pregnancy is currently the best way to reduce congenital syphilis. A focus on overlapping sexual networks and ensuring access to doxyPEP among pregnant people’s sexual partners at risk for syphilis will help.”
—Sean R. Hosein
Resources
Doxycycline to help prevent bacterial STIs – CATIE
Exploring the impact of doxycycline to prevent sexually transmitted infections – CATIE News
Doxycycline for STI prevention shows significantly decreased rates of chlamydia and syphilis in a major clinic – CATIE News
Scientists in France assess antibiotic resistance in people who use doxycycline post-exposure prophylaxis (doxyPEP) – CATIE News
Understanding the impact of the antibiotic doxycycline on the sexual well-being of users – CATIE News
Sexually transmitted and blood-borne infections: Guides for health professionals – Public Health Agency of Canada
Winnipeg researchers warn about rising cases of syphilis-related stillbirths — CATIE News
Views from the front lines: Congenital syphilis — Prevention in Focus
Alberta study underscores the importance of syphilis testing in people who use stimulants – CATIE News
Early access to syphilis screening and treatment needed to prevent stillbirths – CATIE News
U.S. researchers encourage screening for neurological complications of syphilis — CATIE News
REFERENCES:
- Menza TW, Berzkalns A, Cannon CA, et al. The population-level impact of doxycycline post-exposure prophylaxis on syphilis in King County, WA: an interrupted time series analysis. Clinical Infectious Diseases. 2026; in press.
- Bolan RK. Doxycycline prophylaxis for syphilis: proceed with caution. Clinical Infectious Diseases. 2026; in press.
- Osmundson J, Holloway IW, Macias Gil R, et al. Doxycycline postexposure prophylaxis for bacterial STIs: Prescribing patterns, use, short-term outcomes among 2083 patients in a Los Angeles federally qualified health care program, and implications for widespread use. Open Forum Infectious Diseases. 2025 Feb 15;12(3): ofaf089.
- Haaland RE, Fountain J, Edwards TE, et al. Pharmacokinetics of single-dose doxycycline in the rectum, vagina, and urethra: implications for prevention of bacterial sexually transmitted infections. EBioMedicine. 2024 Mar; 101:105037.