CATIE: Scientists in France assess antibiotic resistance in people who use doxyPEP
January 13, 2026
CATIE news story
- Taking doxycycline after sex (doxyPEP) reduces the risk of some sexually transmitted infections
- A French study found gonorrhea less susceptible to some antibiotics for those taking doxyPEP
- Antibiotic resistance was not found for the drug classes typically used to treat gonorrhea
Clinical trials have found that doxycycline taken after sexual exposure—called doxycycline post-exposure prophylaxis, or doxyPEP for short—significantly reduces the risk of developing chlamydia and syphilis. In some cases, doxyPEP can also reduce the risk of gonorrhea. However, in the past, a class of antibiotics called tetracyclines (of which doxycycline is a member) was used to treat gonorrhea, and the bacteria that cause this infection have acquired the ability to resist tetracyclines (and, therefore, doxycycline). As a result, doxyPEP is not always effective at reducing the risk of gonorrhea.
Monitoring the development of gonorrhea-causing bacteria that are resistant to antibiotics is important, as there are dwindling treatment options. Historically, these bacteria have eventually developed the ability to resist many antibiotics.
A study in France
A team of scientists in France has been studying samples (urine, anal and throat swabs) from participants in a study called DOXYVAC. In this clinical trial, gay, bisexual and other men who have sex with men (gbMSM) were randomly assigned to receive doxyPEP (362 participants) or no doxyPEP (183 participants).
The team focused on samples collected between January 2021 and February 2023.
Researchers assessed the ability of gonorrhea-causing bacteria to develop resistance to the following eight antibiotics:
- azithromycin
- cefixime
- ceftriaxone
- ciprofloxacin
- doxycycline
- gentamicin
- spectinomycin
- tetracycline
The scientists found that high-level resistance to tetracycline was more likely in people taking doxyPEP (36%) than in people not taking doxyPEP (13%). This difference was statistically significant; that is, not likely due to chance alone.
Other studies have found increasing rates of high-level tetracycline resistance, likely due to exposure to doxycycline.
Cross-resistance
Sometimes, bacteria that develop the ability to resist one group of antibiotics can also simultaneously develop the ability to resist another group of antibiotics.
In the present study, the scientists did not find increased rates of resistance to other antibiotics that are structurally unrelated to doxycycline.
However, they did find that men who used doxyPEP were more likely to have gonorrhea-causing bacteria with reduced susceptibility to an antibiotic related to penicillin—cefixime. This antibiotic was once the preferred treatment for uncomplicated gonorrhea in Canada and other countries. Cefixime could be taken in pill form, which would have made it an attractive option. However, due to the risk of resistance, today the antibiotic ceftriaxone is the preferred treatment for uncomplicated gonorrhea. Ceftriaxone is given via intramuscular injection (in the case of high doses, it can be given intravenously).
In the present study, the gene associated with reduced susceptibility to cefixime was about three times more common in samples from people taking doxyPEP than in people not taking doxyPEP (32% vs. 10%). This difference was statistically significant.
Cefixime and ceftriaxone are distantly related to penicillin. In theory, some bacteria that develop resistance to cefixime among doxyPEP users could one day also develop reduced susceptibility and eventually resistance to ceftriaxone. However, in the present study, all strains of gonorrhea-causing bacteria remained susceptible to ceftriaxone, the preferred treatment for gonorrhea.
Previous data from the French study confirmed that doxyPEP was an effective option to reduce the risk of chlamydia and syphilis.
Bear in mind
The French researchers stated that data from their study show that doxyPEP is “promising” for reducing the risk of chlamydia and syphilis. However, this strategy is “associated with the selection of [strains of gonorrhea-causing bacteria] with high-level resistance to tetracycline and reduced susceptibility to cefixime.” They added that it will be important to continue to monitor the development of bacteria with the ability to resist antibiotics in people using doxyPEP. The scientists also underscored that their findings add urgency to the development of a vaccine that can reduce the risk of gonorrhea. Such a vaccine could reduce the demand for gonorrhea treatment and help preserve antibiotic options for the future.
Readers should note that the development of resistance to doxycycline by bacteria in the community is significant for other reasons. Doxycycline is an important antibiotic for other sexually transmitted germs, including chlamydia and a variant of chlamydia called LGV (lymphogranuloma venereum). In the U.S., doxycycline is widely used for treating another sexually transmitted infection called Mycoplasma genitalium (in Canada the recommended treatments are azithromycin or moxifloxacin). So, the spread of resistance to doxycycline may have implications for other conditions.
In related developments—Germany and Canada
Germany
Recently, researchers in Berlin reported four cases of gonorrhea in heterosexual men. The men ranged in age from late teens to early 60s and lived in the same geographical region. The men had no obvious connection to each other and none of them had recently travelled outside of Germany. Fluid samples and swabs were sent to a reference laboratory for analysis. The lab found that the men were infected with gonorrhea-causing bacteria with high-level resistance to the antibiotics azithromycin and cefixime. In two of the men, these bacteria also had apparent resistance to concentrations of ceftriaxone that would be achieved with standard dosing.
Three of the men disclosed that they had sex with female sex workers and one of them had sex with a non-regular female partner. The men had inflammation of the urethra, which led to symptoms (these were not detailed but usually include painful urination or difficulty urinating and sometimes a discharge from the penis).
Doctors prescribed relatively high doses of ceftriaxone (2 g for one to three days), given either intravenously or via intramuscular injections, together with high-dose oral azithromycin. Three of the men received this therapy and recovered. German researchers suggest that high doses of ceftriaxone may be able to overcome resistance, at least in these cases.
The fourth man was prescribed antibiotics but he did not go to the hospital for treatment with intravenous ceftriaxone, and medical staff were unable to locate him despite repeated attempts.
The gonorrhea that these men had was related to a strain of gonorrhea reported in the UK in 2024. This UK case was originally connected with travel to Cambodia.
Canada
Scientists in Montreal, Quebec, and at the National Microbiology Laboratory in Winnipeg reported details on a man who became infected with extremely drug-resistant gonorrhea.
In May 2024, a heterosexual man in his 40s who was experiencing urethral inflammation sought care at a clinic in Montreal. He disclosed that he had travelled to Cambodia and had sex with female sex workers there. He did not have sex with anyone in Canada after his return, two months prior to the onset of his symptoms.
His initial treatment was azithromycin (2 g) and cefixime (800 mg), both drugs taken in pill form once. Two weeks after taking his treatment, he was still experiencing symptoms.
His second round of treatment consisted of one dose of ceftriaxone (250 mg) given via intramuscular injection and oral doxycycline (100 mg twice daily for seven consecutive days). Unfortunately, this treatment also failed, and he continued to experience symptoms. What’s more, lab analysis of his urine found gonorrhea-causing bacteria.
This man’s third round of treatment consisted of continued oral doxycycline (as before), but this time the doxycycline was prescribed under the assumption that he might have chlamydia infection that was affecting his urethra. He was also given a higher dose of ceftriaxone (500 mg) via intramuscular injection. This higher dose is now the recommended treatment for uncomplicated gonorrhea in Canada. He subsequently recovered and analysis of his urine found that he was free from gonorrhea.
—Sean R. Hosein
Resources
Canada raises dose of preferred antibiotic for gonorrhea – CATIE News
Gonorrhea guide: Key information and resources – Public Health Agency of Canada
Sexually transmitted and blood-borne infections: Guides for health professionals – Public Health Agency of Canada
Chlamydia and LGV guide: Treatment and follow-up – Public Health Agency of Canada
Gonorrhea – CATIE
New antibiotic (gepotidacin) looks promising for gonorrhea – CATIE News
TreatmentUpdate 245 – CATIE
Doxycycline for STI prevention shows significantly decreased rates of chlamydia and syphilis in a major clinic – CATIE News
Doxycycline to help prevent bacterial STIs – CATIE
REFERENCES:
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- Maatouk I, Vumbugwa P, Cherdtrakulkiat T, et al. Antimicrobial resistance in Neisseria gonorrhoeae in nine sentinel countries within the World Health Organization Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP), 2023: a retrospective observational study. Lancet Regional Health – Western Pacific. 2025 Aug 21; 61:101663.
From Canadian AIDS Treatment Information Exchange (CATIE).
This content was originally published by CATIE, Canada’s source for HIV and hepatitis C information.
Source: CATIE:
https://www.catie.ca/catie-news/large-and-long-french-study-explores-changes-in-cancer-risk-among-people-with-hiv
For more information visit CATIE's Information Network at www.catie.ca
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