Drug resistance and Doxy PEP: Should we worry?

In late 2022, the San Francisco Department of Public Health and San Francisco AIDS Foundation began recommending an STI prevention strategy called “Doxy PEP” to certain groups of people who may be at risk for STIs. The strategy involves taking the antibiotic doxycycline after sex in order to prevent bacterial STIs including chlamydia, syphilis, and gonorrhea from being acquired. 

Since we made this recommendation, we’ve received some questions from community members about how this approach may contribute to drug resistance–and if that’s a concern for people to be aware of before beginning Doxy PEP. Here are my thoughts on Doxy PEP and drug resistance. 

(And as with any medical decision, we recommend having a conversation with your healthcare provider about the possible benefits and concerns before beginning Doxy PEP.)  

First, what is antibiotic drug resistance?

Antibiotic drug resistance refers to instances when bacteria aren’t affected by the medications used to kill or destroy them. When bacteria are able to live and multiply, even in the presence of an antibiotic, we say that the bacteria are “drug resistant” to antibiotics.  

How does drug resistance develop? 

Antibiotic drug resistance develops when bacteria mutate in response to an antibiotic, often at a low or ineffectual dose (but this can also occur even when the antibiotic is taken as prescribed). Without rigorous testing and treatment, resistant infections can spread throughout populations. 

If you’ve ever been prescribed an antibiotic to take for an infection, you’ve probably been asked to take the medication for the entire length of time that it has been prescribed–even if your symptoms seem to go away. That’s partly because if you stop taking the antibiotic early, there’s a risk that some of the bacteria may survive and develop, or acquire from other bacteria around them, defenses to overcome the effects of the antibiotic. These defenses can include genetic mutations to make the antibiotic ineffective, pumps to push the antibiotics out of their cells, or enzymes to destroy the antibiotic before it can work. If this infection then spreads to other people, the infection may not be treatable by the same type of antibiotics.  

It’s important to note that drug resistance can and does develop in individual people taking antibiotics, including Doxycycline. 

What is the problem with drug resistance? 

The problem with drug resistance is that healthcare providers lose the ability to treat drug resistant-infections with the medications available to them. Bacterial infections become harder and harder to treat as drug resistance spreads. 

Gonorrhea is one bacterial infection that you have heard about drug resistance toward–over time, gonorrhea bacteria have slowly developed resistance to antibiotics used to treat gonorrhea. 

In 2006, CDC had 5 recommended treatment options for gonorrhea. Since 2015, there has only been one recommended first-line treatment (a combination of two drugs), after widespread resistance to a commonly-used medication named cefixime developed and spread. An estimated 30% of new gonorrhea infections in the U.S. are resistant to at least one antibiotic. 

Could Doxy PEP cause drug resistance? 

A recent review of the impact of oral tetracyclines (the class of antibiotics to which doxycycline belongs) did suggest “modest and transient” evidence of bacterial resistance developing in oral, gut, and respiratory bacteria that were studied. Researchers are currently studying the impact of doxycycline for STI prevention on development of resistance for gonorrhea; as well as other bacteria that may be around and not the target of the antibiotic. Resistance to syphilis and chlamydia is less of a concern, as these bacteria have few mechanisms to develop resistance and significant resistance has not been seen to doxycycline with these two infections (in fact, Penicillin is still first-line treatment for syphilis).  

Drug resistance with Doxy PEP is something that is being studied on an individual level with people who are taking Doxy PEP for STI prevention. The broader public health impacts of Doxy PEP on drug resistance is something that current clinical trials will not answer, and highlights the importance of ongoing public health evaluation as this intervention becomes available. This is something that San Francisco AIDS Foundation feels strongly about and contributes to–we share data with public health partners in order to track cases of gonorrhea resistance, as well other infections where resistance may be of concern such as breakthrough infections among people taking PrEP. 

Resistance will always be a potential risk. But do the benefits of using antibiotics to prevent infections outweigh the potential costs? For individual clients and patients, the answer to this question is clear in my mind. As a physician, my first priority is ensuring effective, evidence-based care for the clients and people I and my staff see. Offering Doxy PEP to people who are eligible for this intervention is in line with this: we have strong, compelling evidence that Doxy PEP works to prevent STIs that are becoming more and more common in San Francisco. For individual people who either choose not to use condoms, who do not like using condoms, or who find that condoms do not work well in their lives–I as a clinician can offer them all the available STI prevention options by offering Doxy PEP. 

On an individual and population level, drug resistance will likely occur with the increased use of Doxy PEP, especially with the amount of doxycycline that will be indicated for many users. The extent to which this happens, and the impact, are still open questions, and must be carefully monitored. It is true that we are taking a calculated risk by rolling out Doxy PEP to people who may benefit from this strategy. But this decision is supported by a very strong belief that our communities will benefit dramatically from Doxy PEP, even though there is a risk of resistance. There is an important balance in these considerations, and one that is not made lightly by the medical community. This new intervention truly has the ability to change the landscape of STI prevention in San Francisco–much as PrEP has changed the landscape of HIV prevention. 

A final note I’ll add is that some of the conversation around drug resistance with Doxy PEP is likely fueled by stigma, bias, and homophobia. The idea that we would withhold an effective, evidence-based prevention intervention from gay, bi, and Queer men, and trans folx having condomless sex is simply unacceptable. They may ask the question, “why not just use condoms?” We’ve heard it all before, especially when PrEP rolled out more than 10 years ago. Perhaps you remember concerns around “risk compensation” with PrEP in addition to concerns around drug resistance with increased use of PrEP. Yes, we can and do recommend condoms as one way to prevent HIV and STIs. And yes, at the same time we recognize that many people do not use condoms and will never use condoms. We’re here to meet people where they are–with no stigma or shame–and provide them with the tools they need to live well. 

The bottom line 

It is possible that Doxy PEP may contribute to drug resistance on an individual and population level, and this is a concern that is currently being studied. Doxy PEP is an individual decision and folks will need to weigh the benefits (STI prevention) with possible risks, as with any medical decision. 

Other jurisdictions are taking a more conservative approach on supporting Doxy PEP roll-out, and we are proud that our public health leaders, infectious disease physicians, and community partners in San Francisco moved quickly to translate this new science into implementation. Reducing medical problems from syphilis, gonorrhea, and chlamydia is a top public health priority. These infections can be painful, stigmatizing, and can cause serious medical complications. In short, the overall benefits of Doxy PEP outweigh the risks, and we will continue to support the science, and incorporate new findings, so that we can make the best recommendations for our communities.