Using antibiotics to prevent STIs

Maybe you’re considering using antibiotics to prevent sexually transmitted infections (STIs). Or maybe this is already part of your sexual health routine. If either is the case, this information is for you, as there are some important points to consider.

It is important to keep in mind that most medical guidelines don’t yet recommend using antibiotics in this way. There remains a concern about whether it may lead to the spread of bacteria that are resistant to an antibiotic needed to treat a wide range of infections.

This page presents some of the research that has been done and the potential pros and cons of using this approach. So far, most of the research has been done with gay and bisexual men; one study with cisgender women in Kenya had disappointing results.

What is STI prophylaxis?

STI prophylaxis involves taking an antibiotic pill to prevent bacterial STIs, such as syphilis and chlamydia.

So far, research has focused on taking a single dose soon after sex. This is considered post-exposure prophylaxis (STI PEP) – the antibiotic seems to prevent bacterial growth and makes it less likely for exposure to lead to infection.

Another approach would be to take a daily dose of the antibiotic – this would be considered pre-exposure prophylaxis (STI PrEP), meaning that there may be enough of the antibiotic in the body before exposure occurs.

This page focuses specifically on using antibiotics to prevent bacterial STIs, which is still an experimental technique. It is not to be confused with HIV PrEP and PEP, which are effective forms of preventing HIV, as outlined below.

	Medication	Does it prevent HIV?	Does it prevent bacterial STIs?
STI pre-exposure prophylaxis (STI PrEP or doxyPrEP)	Doxycycline (antibiotic)	No	Research ongoing, but may work against chlamydia, syphilis and gonorrhoea.
STI post-exposure prophylaxis (STI PEP or doxyPEP)	Doxycycline (antibiotic)	No	Effective for gay and bisexual men in three studies; research in other populations is ongoing. Works against chlamydia and syphilis and, to some extent, gonorrhoea.
HIV pre-exposure prophylaxis (HIV PrEP)	Tenofovir / emtricitabine (two antiretrovirals)	Yes	No
HIV post-exposure prophylaxis (HIV PEP)	Raltegravir / tenofovir / emtricitabine (three antiretrovirals)	Yes	No

Does taking antibiotics to prevent STIs work?

Three key studies have shown the effectiveness of using an antibiotic called doxycycline preventatively.

Doxycycline prevents bacteria from reproducing and effectively treats various bacterial infections, including pneumonia, gum disease, skin infections and some STIs. Doxycycline is also used to prevent malaria infection. There is no evidence to suggest that using any other antibiotics than doxycycline would prevent STIs.

Research has largely been carried out with gay men who have multiple sexual partners and don’t use condoms, as they represent the group at highest risk for recurrent bacterial STIs. In each study, some participants were instructed to take a 200mg doxycycline dose (two 100mg pills) within 24 hours after sex (and no later than 72 hours after) – this is doxycycline post-exposure prophylaxis, or doxyPEP.

A French trial recruited 232 gay and bisexual men who were already taking PrEP for HIV, and at a high risk for contracting bacterial STIs. They were randomised to two groups: those in the experimental group were given doxycycline to take after sex and men in the other group did not take any antibiotics.

Over a follow-up period of around nine months, there were 47% fewer infections with one of the three main bacterial STIs (syphilis, chlamydia and gonorrhoea) in the men taking doxycycline. While the antibiotic had no effect on gonorrhoea, with similar numbers of infection between both groups, there were 70% fewer chlamydia infections and 73% fewer syphilis infections in the men taking doxycycline when compared to those not taking it.

The gonorrhoea finding was perhaps not surprising: around half of the French and two-thirds of the UK strains of gonorrhoea, and around a quarter of those in the US, are resistant to tetracycline antibiotics (doxycycline belongs to this class). However, these antibiotics are not usually used in the treatment of gonorrhoea because of the high rates of resistance (see the section below What about resistance?).

A second large study – the US DoxyPEP study – reported results in July 2022. A total of 501 gay and bisexual men and trans women who were either living with HIV (174) or taking HIV PrEP (327) were randomised to either take doxyPEP or to not receive any antibiotics. As with the French study, the participants were at a higher risk of contracting bacterial STIs, with just under half of the group reporting either gonorrhoea, chlamydia or syphilis in the past year. Participants were tested for STIs every three months.

Overall, there was a 65% reduction in the incidence of all STIs per quarter in both those living with HIV and those taking HIV PrEP. In fact, the study was stopped a year early because of the high effectiveness, with a recommendation for participants in the control groups to receive doxyPEP too.

In terms of specific STIs, doxycycline worked well to prevent chlamydia, syphilis and gonorrhoea, unlike in the French study. For people living with HIV, there was a 74% reduction in chlamydia, 77% reduction in syphilis (not statisitically significant, possibly due to the low number of syphilis infections) and a 57% reduction in gonorrhoea. For people taking HIV PrEP, there was an 88% reduction in chlamydia, 87% reduction in syphilis and 55% reduction in gonorrhoea.

One of the possible reasons for the gonorrhoea finding is that tetracycline resistance in gonorrhoea is not as widespread in the US as it is in France or the UK. An analysis of gonorrhoea resistance among participants in this study showed only modest increases in the proportion of gonorrhoea infections with significant resistance, with little difference between those taking doxyPEP and those not taking it.

A third large study – the Doxyvac study – by the same French research group as the trial mentioned above, presented results in February 2023. From a sample of 502 gay and bisexual men on HIV PrEP, 332 were randomised to take doxyPEP (200 mg within 72 hours after sex as in prior studies), while the rest did not take doxycycline. As with the previous trial, these men had high rates of bacterial STIs diagnosed in the past year – 68% had had gonorrhoea, 50% chlamydia and 20% syphilis. Participants were tested for STIs at baseline, and every three months, or if they presented with symptoms, for a median period of nine months of follow-up.

DoxyPEP was found to be highly effective again, reducing incidence rate or the first documented episode of chlamydia and syphilis by 89% and 79%, respectively. An unexpected finding was that the incidence rate of gonorrhoea also decreased by 51%. This was unexpected due to the results from the first French trial and the high tetracycline resistance in gonorrhoea seen in France. As with the US DoxyPEP study, this study was also stopped early, with all participants being offered doxycycline due to its high effectiveness.

This study also investigated the effectiveness of a vaccine (the same one used to prevent meningitis B) against gonorrhoea. While it was initially reported that the vaccine resulted in a 51% reduction in incidence of gonorrhoea, the researchers say that there may have been an error in their original analysis and that this result needs to be verified.

The only study done with cisgender women participants – the dPEP Kenya trial – found that doxyPEP was not effective at preventing bacterial STIs among 449 women taking HIV PrEP. Between 2020 and 2022, non-pregnant cisgender women with a median age of 24 were randomised to either take doxycycline after sex, or to receive standard-of-care management (quarterly STI testing and treatment after diagnosis). All women were tested for STIs quarterly.

STI rates were high during the study, with an annual incidence of 27%. However, doxyPEP was ineffective at reducing the number of STIs, with no statistically significant differences detected between the treatment and standard-of-care groups for chlamydia or gonorrhoea. There was only one case of syphilis. It is unclear exactly why doxyPEP was ineffective for cisgender women in this study. Possible reasons include anatomical differences, suboptimal adherence and high rates of doxycycline resistance. Doxycycline-resistant gonorrhoea is much more common in this context than elsewhere, but this does not account for the chlamydia finding. Further research is needed to establish the effectiveness of doxyPEP among cisgender women.

All the studies mentioned so far involved taking a single dose of the antibiotic after sex (doxyPEP). There has been much less research into the daily use of the antibiotic (doxyPrEP). However, a small US pilot study randomised 30 gay men living with HIV, who had had syphilis twice or more since their HIV diagnosis, to one of two groups. Men who took 100mg of doxycycline by mouth daily were 73% less likely to test positive for gonorrhoea, chlamydia or syphilis during 48 weeks of follow-up, compared to men who had been provided with monetary incentives to remain STI free. There was no significant difference in reported risk behaviours between the two groups.

So, while three studies have showed positive results for doxyPEP among gay men and trans women (taking the medication after sex), there is a lack of data on doxyPrEP (daily dosing). While the efficacy of doxyPEP is promising, larger studies with longer follow-up are needed to understand the impact on rates of resistance. Further research with cisgender heterosexual women and men is needed. A study into the use of doxyPrEP by gay and bisexual men in Australia is underway, while other researchers plan to compare doxyPrEP and doxyPEP among gay and bisexual men in Canada.

Why most guidelines don’t recommend this

Soon after the US DoxyPEP study reported its results, the San Francisco Department of Public Health recommended doxyPEP to gay and bisexual men and transgender women who are at a higher risk of contracting bacterial STIs, especially those who have had syphilis in the past. Other public health agencies have been slower to respond to the new data, in part due to concerns about STI prophylaxis.

The US Centers for Disease Control and Prevention has issued considerations regarding the use of doxyPEP, but have yet to provide clearer guidance. This is still considered an off-label use of the antibiotic.

The Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine has issued interim guidance outlining the evidence in favour of doxyPEP’s effectiveness. They urge clinicians to consider adverse outcomes associated with long-term use, such as resistance and changes to the gut microbiome.

In most instances, healthcare professionals treat STIs based either on symptoms, the results of laboratory tests, or both. As STIs don’t always have symptoms (but could still cause long-term damage or complications), it is recommended that people who have sex that puts them at risk test frequently and treat any STIs as soon as they are detected. It is also important to make sure that recent partners are treated.

Taking antibiotics prophylactically (to prevent STIs before any symptoms or testing positive) is not recommended yet, mainly due to major concerns about the development of antimicrobial resistance. Taking a drug and then (despite prophylaxis) catching an infection that easily develops resistance to it could further raise rates of resistance to that drug in the wider community. Resistance means that medications that were once effective at treating certain bacterial infections lose their ability to do so. Essentially, the bacterium outsmarts the medication, rendering it ineffective.

Resistant strains circulate within the population, resulting in the failure of treatments that had previously worked – even in people not using antibiotics to prevent STIs. Gonorrhoea has evaded multiple classes of antibiotics, and few options remain available. Most recently, it has become resistant to azithromycin and therefore, this antibiotic is no longer recommended for treatment.

There is a danger of running out of antibiotics that work to treat a resistant strain; this complicates treatment and could negatively impact upon health outcomes. Resistance is a concern both for bacteria that cause STIs and other common infections.

However, when it comes to using specific antibiotics to prevent specific STIs, it’s not all bad news – see more under What about resistance?

Who could benefit from using antibiotics for STI prophylaxis?

The available evidence of effectiveness of STI prophylaxis only applies to gay and bisexual men and transgender women. The single study conducted with cisgender women did not show effectiveness.

People at the highest risk of contracting bacterial STIs, especially those who may be at risk for repeated infections, might benefit from STI prophylaxis. If you do not use condoms consistently, or at all, have multiple sexual partners and have had bacterial STIs in the past, you may be interested in the potential of this approach.

Bacterial STI prophylaxis can be taken regardless of HIV status. Many individuals who are HIV negative and on HIV PrEP use condoms less frequently or have stopped using them altogether. Similarly, some people who are living with HIV also choose not to use condoms all of the time as an undetectable viral load prevents HIV transmission.

An accepted public health approach promotes the control of STIs among those at highest risk as a way of reducing STIs in the general population. An Australian modelling study supports this notion: it estimated that if half of Australian gay men took doxycycline as PrEP, and it was 70% effective against syphilis, then rates of syphilis would decrease by 50% after a year and 85% after a decade. Interestingly, the same finding applied if only 50% of the highest-risk group (men with more than 20 partners in six months) were taking doxycycline. This indicates that targeted interventions could have widespread community-level benefits.

Surveys in Australia, the US and the UK show high levels of interest among gay men and some healthcare providers in using doxycycline to prevent STIs, with some men already using this approach. However, one UK survey showed that among those who said they had used STI prophylaxis, only 56% had used doxycycline, others had used antibiotics such as amoxicillin (20%) and azithromycin (18%). There is no evidence to suggest that antibiotics other than doxycycline would be at all effective in preventing STIs.

For some groups, such as sex workers, negotiating condom use can be challenging and biomedical forms of prevention, such as HIV PrEP, have been a crucial form of protection. STI prophylaxis could be another valuable protective tool in this instance.

When would be the best time to take antibiotics to prevent an STI?

Based on the available doxyPEP research and the San Francisco guidelines, those at risk for exposure to bacterial STIs would need to take a 200mg dose after a sexual encounter (ideally within 24 hours and no later than 72 hours). No more than one dose should be taken every 24 hours.

There is less certainty over whether daily dosing (doxyPrEP) works, but a 100mg pill every day is being tested in studies.

A small qualitative study with Australian gay men indicated a preference for daily dosing. However, taking doxycycline as doxyPEP – as opposed to taking it daily – might be best in terms of reducing the amount of antibiotics taken.

What about resistance?

STIs are caused by different strains of bacteria and are treated with antibiotics that are known to be effective against the specific bacterium that causes the infection. In some cases, an antibiotic that previously worked stops working, because the bacterium has developed resistance to it.

Doxycycline has been used prophylactically and as long-term treatment in various instances, and thus, there is less of a concern regarding antimicrobial resistance with this particular drug.

Gonorrhoea: some strains are resistant to doxycycline, so the drug may vary in its effectiveness at preventing gonorrhoea depending on the context, as was documented in the first French and Kenyan studies. Nonetheless, some findings have shown that doxyPEP reduces rates of incident gonorrhoea. Importantly, doxycycline is not used to treat gonorrhoea. This means that use of doxycycline as prophylaxis should not complicate the treatment of a gonorrhoea infection, should one occur.

Syphilis: there is currently no evidence of doxycycline resistance in syphilis, although there is always the concern that it could develop as doxycycline is the first choice for treating syphilis in people who are allergic to penicillin. Recently, syphilis developed high level resistance to the antibiotic azithromycin within a few years of it being used as syphilis treatment.

Chlamydia: doxycycline is the first-line treatment for uncomplicated chlamydia in the UK and other countries. This means that the development of doxycycline resistance would be a serious concern with very few available treatment options remaining. There have been some cases of doxycycline treatment failure, but the studies did not test for resistance and the causes of treatment failure are unclear. Encouragingly, many studies in communities which frequently use doxycycline have not found evidence for resistance in chlamydia.

Mycoplasma genitalium (MG): there is concern about resistance to this STI which is a frequent cause of urethritis (an inflammation of the urethra – the tube that carries urine out of the body) in men. Doxycycline is a recommended alternative medication to treat uncomplicated MG because of emerging resistance to first-line treatments, such as azithromycin. More widespread use of doxycycline among those with high prevalence of MG, such as gay men, could become an issue in future and requires further research.

Other infections: doxycycline is an important treatment for community-acquired pneumonia and other infections. Continued exposure to doxycycline is therefore a concern in terms of causing resistance in other organisms that are not sexually transmitted. This would limit treatment options for the individual and others in the future.

For instance, among people taking doxycycline in the US DoxyPEP study mentioned above, there was a significant 8% increase in the number of samples of Staphylococcus aureus (a bacterium that is usually present in the nose and throat) that were resistant to doxycycline. However, researchers stated that overall, the numbers of new doxycycline-resistant bacteria that emerged were small and that population-level monitoring will be important once doxyPEP becomes more widely used.

What about side effects?

Doxycycline is generally safe and well-tolerated. This is true even when it is used for long periods of time, as is the case when it is used to treat acne and as malarial prophylaxis. The most common side effects are gastrointestinal, such as diarrhoea, vomiting and nausea. Increased sensitivity to light can also be a concern with prolonged use. In most instances, side effects resolve once doxycycline is discontinued.

Doxycycline should not be used by pregnant people, or those who might become pregnant.

There is also concern regarding how ongoing antibiotic use affects the gut microbiome, including the impact on good bacteria and overall health. In the first French study mentioned above, only eight of 232 men discontinued doxycycline due to gastrointestinal side effects. In the US DoxyPEP study, there were no serious adverse events reported and only 1.5% of the study group discontinued due to intolerance or participant preference. In fact, 88% reported that doxyPEP was either acceptable or very acceptable. Similarly, there were no serious adverse events related to doxycycline during the Doxyvac study, with only three participants discontinuing treatment due to side effects such as nausea, abdominal pain and diarrhoea.

The two most common formulations are monohydrate and hyclate, with monohydrate (or coated hyclate) generally better tolerated.

Summing up

Three rigorous studies have shown that doxyPEP (taking doxycycline soon after sex) prevents STIs when used by gay and bisexual men, and one of the studies showed it worked for trans women too. Based on one study so far, doxyPEP appears to be ineffective at preventing STIS among cisgender women. More research is needed with this group.

Potential bacterial resistance needs to be monitored at a population level with increased regular use of doxycycline; this should be balanced by the potential benefits doxyPEP has to offer, especially among gay men and trans women with recurrent STIs.

While most public health agencies have not yet endorsed using doxycycline to prevent bacterial STIs, some sexual health doctors may be willing to give informal advice or to prescribe the drug outside the terms of its licence.