Doxycycline post-exposure prophylaxis (doxy PEP) is rapidly growing in popularity in the United States, Germany, and Australia. We have an opportunity to use this approach to greatly lower the risk of acquiring sexually transmitted infections (STIs). Yet just as rapidly, alarm bells are being sounded about its role in exacerbating antibiotic resistance. When used preventively, doxy PEP works very well to stop infections before they even start. Experts are cautioning that the benefits may be short-lived and come with significant risks.
Doxy PEP is administered within 72 hours of unprotected sexual exposures. This treatment is highly effective in preventing the transmission of sexually transmitted infections such as gonorrhea and chlamydia. Though widely adopted in other countries, it is still not endorsed in the United Kingdom or the Netherlands. This chasm between recommendations is alarming, and we fear for its long-term effects on public health.
Growing Evidence of Resistance
Recent studies have highlighted a troubling trend: as the use of doxy PEP expands, so too does the incidence of antibiotic resistance among bacterial pathogens. Tetracycline resistance has reached an all-time high, particularly in the Pacific Northwest. It soared from a mere 2% of cases in early 2021 to an astounding 65% by mid-2024. This statistic highlights the importance of urgent, but thoughtful planning to assess doxy PEP’s broader impact.
In that context, our research team has been vocal about the potential for the doxy PEP benefits to be short-lived. Jeanne Marrazzo, an expert in infectious diseases, stated, “I think it’s a hard genie to put back in the bottle,” referring to the challenges of reversing antibiotic resistance once it has become established. She voiced concerns about the call to end doxy PEP even though a new study is saying otherwise.
“We won’t have the ability to do this type of analysis if we lose the resources that CDC has available for it.” – Jeanne Marrazzo
A recent study in Eurosurveillance looking at 1,633 MSMs, transgender women, and gender-diverse persons in the Netherlands. It discovered that 22% of them said they used doxy PEP or pre-exposure prophylaxis (PrEP) informally. Alarmingly, 15% had used doxy PEP in the past and 65% had high intention to use doxy PEP. These findings should sound alarm bells for the need for oversight and guidelines regarding its use.
Assessing Benefits and Risks
Providing doxy PEP to high-risk populations is a no-brainer. The benefits vs. risks scale is still very much in the balance. Yonatan Grad, one of the principal researchers in the field, put it succinctly. He emphasized that encouraging high-risk people to use doxycycline prophylactically is super effective at reducing STI rates. He warned that the increasing emergence of drug-resistant strains represents a grave danger to the health of our communities.
“It’s less a theoretical concern now and more [that] we have evidence to indicate that it’s happening.” – Yonatan Grad
Grad further elaborated on the implications of antibiotic resistance: “The idea being that, of course, taking antibiotics drives resistance. You’ll see it not only in the thing you’re targeting but anything else that happens to be on you and in you.” Doxy PEP provides on-the-spot protection against some STIs. It also, perhaps unintentionally, constrains the treatment possibilities for other infections.
Marrazzo remarked on the potential need for alternative solutions: “As I’ve been saying for ages and others are too, it really needs to be seen as a bridge to an effective vaccine for [gonorrhea].” Developing a vaccine would remove the need for troublesome antibiotics such as doxycycline.
Recommendations Moving Forward
In light of these advances, we call upon those that are responsible for developing healthcare strategies to implement doxy PEP to rethink their approach. The Centers for Disease Control and Prevention (CDC) is monitoring usage patterns and resistance trends closely. Evidence is rapidly accumulating about the risks associated with doxy PEP. Experts overwhelmingly call for strong, comprehensive public health policies that prioritize prevention and responsible use of antibiotics.
Ceftriaxone remains our first line treatment for gonorrhea. The good news, according to experts, is that the rising resistance to doxycycline does not make ceftriaxone any less effective. The rosy picture makes for a dangerous backdrop as resistant strains continue to breed. Our medical community needs to come together to prevent return to unsafe practices while we fight the battle against STIs.
