Prevention vs. resistance: The doxyPEP dilemma

It seems that everyone is taking doxyPEP now. Every day in my clinic, people ask me about it, often conflating it with HIV PrEP. Many believe that if they are on doxyPEP, worrying about sexually transmitted infections (STIs) will be a thing of the past.

DoxyPEP involves taking an antibiotic called doxycycline after sex to help prevent bacterial STIs and has been primarily studied in gay, bisexual and other men who have sex with men (gbMSM), as well as trans women. What we know from these studies is that there is a benefit for individuals, specifically gbMSM and trans women, in taking doxyPEP. With proper use of doxyPEP, there is a decrease in STIs, particularly chlamydia and syphilis, with a much smaller effect on gonorrhea. While the individual risks of a course of doxyPEP are small, mainly consisting of gastrointestinal upset or rash with exposure to sunlight, larger public health concerns over antimicrobial resistance (AMR) haven’t been resolved. AMR is when microorganisms (like bacteria) develop the ability to overcome previously effective medications and has been listed as a global health threat by the World Health Organization (WHO).

Why does this matter?

First, let’s take a step back. Many of us know that antibiotics are medications used to treat bacterial infections. For this conversation, it’s also important to know that multiple antibiotics are grouped into “classes” based on their chemical structure and how they work. It is possible for bacteria to develop antimicrobial resistance to one or more antibiotics or to one or more entire classes of antibiotics.

Doxycycline is one of the most effective drugs we use for the treatment of some bacterial STIs. Recently, studies on doxyPEP have shown, not surprisingly, increased doxycycline resistance in gonorrhea among people taking doxyPEP, and also reduced effectiveness of another antibiotic, cefixime, in those organisms. This raises concerns for potential increases in resistance to a related drug called ceftriaxone in the future. And while resistance to tetracyclines (the class of antibiotics doxycyline belongs to) has not been demonstrated with syphilis we know that it can acquire resistance; we have seen emerging resistance in syphilis to another class of antibiotics called macrolides over the past few years. Additionally, there have been reports of tetracycline resistance in chlamydia although these are rare.

“But wait,” some will say. “Haven’t we been using doxycycline to treat acne for years? Why does this not raise alarm bells, but prescribing doxy for gay men to prevent syphilis does? Maybe it’s just homophobia, rearing its ugly head again; let’s be a little more sex positive…”

Unfortunately, the arguments around the use of tetracyclines for acne don’t hold water when we are talking about doxyPEP for STIs. First, doxycycline for acne is used as much for its anti-inflammatory effects as its antimicrobial effects. Second, in terms of acne treatment, the organism usually targeted by doxycycline is a slow-growing bacterium compared to many other common organisms. The slow growth can mean that there is less opportunity to acquire resistance mutations, compared to STIs. Third, acne is not considered a transmissible infection, much less a sexually transmitted one — we don’t have outbreaks of cystic acne among teenagers after a school dance. And regardless, multiple studies have shown that the rate of resistance to doxycycline in its treatment for acne has been increasing over the years, coinciding with increases in doxycycline usage.

So, what does all this mean?

Should we avoid doxyPEP altogether? Not at all, but we need to be aware of both the promise and the potential perils of using this new tool. First, if someone hasn’t had an STI in the past 12 months, they don’t need to use doxyPEP; all of the studies were in individuals with a history of a recent bacterial STI. Also, do you need to use doxyPEP every time you have sex? If you’re having sex with a regular partner, probably not. However, there are also some great times to use doxyPEP, such as if you’re going on the gay cruise (the one on the water) or going gay cruising (the one in the bushes)! Encounters with new sexual partners and times of higher sexual activity like Pride or vacations are all good times to consider using doxyPEP. Having a nuanced approach to the use of doxycycline to prevent STIs can help to preserve its utility in the future and avoid widespread antimicrobial resistance.

Dr. Kevin Woodward is an associate professor of medicine in the Department of Infectious Diseases at McMaster University. He is also the executive and medical director of the HQ Health Hub in Toronto. During the course of his career, he has worked at St. Joseph’s Healthcare Hamilton in inpatient infectious diseases, as well as clinical work in the areas of HIV and sexual health. He is involved in provincial and national projects for HIV prevention and PrEP.