DoxyPEP and antibiotic resistance: What have we learned so far?
Studies have found that the antibiotic doxycycline, when taken after sexual exposure, can significantly reduce the risk of some bacterial sexually transmitted infections like chlamydia and syphilis. However, it is generally less effective at reducing the risk of gonorrhea.
Some researchers are concerned that over the long term, widespread use of doxycycline as post-exposure prophylaxis (doxyPEP) may diminish the antibiotic’s effectiveness, or even weaken the efficacy of some other antibiotics.
Is this concern realistic? And if so, are the benefits worth the risk?
Clinical trials
The initial clinical trial of doxyPEP in San Francisco and Seattle found low rates of bacteria developing resistance to doxycycline. In that study of just over 500 people, scientists even found that it had reduced the risk of developing gonorrhea, in addition to chlamydia and syphilis.
However, as doxyPEP gets rolled out in other cities and regions, its effectiveness in preventing gonorrhea may not be as potent as in the original study. The reason for this is that the family of antibiotics to which doxycycline belongs – tetracyclines – was previously used to treat gonorrhea. Eventually, gonorrhea-causing bacteria developed resistance to tetracyclines, and this resistance is still present among strains of gonorrhea in circulation in the world.
For instance, in parts of Europe such as France, where tetracyclines were once extensively used to treat gonorrhea, the bacteria have developed widespread resistance to doxycycline. A clinical trial of doxyPEP in France found that it significantly reduced the risk of developing chlamydia and syphilis, but not gonorrhea.
Growing antibiotic resistance
The most effective treatment for gonorrhea is currently ceftriaxone. This is given by intramuscular injection deep into the buttocks. Ceftriaxone is also used to treat other serious bacterial infections, such as some forms of bacterial pneumonia.
Over the past several decades, the germs that cause gonorrhea have gradually been developing the ability to resist treatment with ceftriaxone. In response, public health authorities have raised the recommended dose. This has helped keep the antibiotic an effective option for gonorrhea treatment. This is particularly important because ceftriaxone, which is available in generic form, is relatively cheap compared to similarly powerful alternatives.
Recently, newer antibiotics have been developed to treat gonorrhea: gepotidacin and zoliflodacin. However, these have not yet been approved for use in Canada. If and when they are approved in Canada, they will likely be more expensive compared to generic ceftriaxone.
Resistance
Sometimes bacteria that develop resistance to one antibiotic develop resistance to other antibiotics as well, particularly ones in the same family of antibiotics.
A team of scientists in France has been studying samples from participants in a study called DOXYVAC. In this clinical trial, men who have sex with men were randomly assigned to receive doxyPEP or no doxyPEP.
In a recent DOXYVAC sub-study, the scientists found that men who used doxyPEP were more likely to have gonorrhea-causing bacteria with reduced susceptibility to the antibiotic cefixime. This antibiotic is structurally different from doxycycline and other tetracyclines and was once the preferred treatment for uncomplicated gonorrhea in Canada and other countries.
Cefixime and ceftriaxone are both structurally related to each other. 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.
What does this mean?
The French scientists underscore that doxyPEP works and that its use should be limited to people at high risk for bacterial sexually transmitted infections. What’s more, the news from the French study is a signal that more research needs to be funded to investigate the long-term risk of bacteria developing resistance to antibiotics. In the meantime, doxyPEP continues to be an important option for preventing STIs, particularly chlamydia and syphilis.
Public health authorities have weighed the benefits (reduced transmission of certain bacteria) over the theoretical risks of antibiotic resistance. An expert advisory committee to the Public Health Agency of Canada recently published a guideline that suggests healthcare providers offer doxyPEP to trans women and cisgender gay and bi men at risk for bacterial sexually transmitted infections.
We look forward to future studies to monitor the ongoing risk of antibiotic resistance, and increased public investment in the research and development of new antibiotics. New antibiotics might not generate enough profit to incentivize commercial investment, so it is up to governments and non-profit funders to address this urgent public health need.
Sean Hosein is CATIE’s science and medicine editor. He has been the writer of CATIE’s flagship TreatmentUpdate since 1989.