Printed on: December 21st, 2024

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Prophylaxis for sexually transmitted infections

Prophylaxis for sexually transmitted infections

This article discusses the use of antibiotics as prophylaxis for NON-HIV STIs. For details of pre- and post-exposure prophylaxis (PrEP and PEP) for HIV, you may find our articles on those topics helpful.

Evidence from cross-sectional surveys suggests that the use of antibiotics as prophylaxis against syphilis, chlamydia and other STIs is increasing. The 2019 HIVPrEP survey found that 9% of respondents reported using prophylaxis. This was associated with high-risk behaviours such as having had ≥5 condomless sex partners in the past 6 months, having had chemsex in the past 12 months or having had an STI in the past 12 months. This is on a background of limited evidence of benefit and risks of antimicrobial resistance.

What is our role in primary care if a patient approaches us for advice on this issue?

This article was updated in June 2024.

In 2021, the British Association for Sexual Health and HIV (BASHH) and UKHSA published a joint position statement against the use of antibiotics as pre- or post-exposure prophylaxis against STIs (BASHH Position statement on Doxycycline as Prophylaxis for Sexually Transmitted Infections 2021).

• Doxycycline taken as pre- or post-exposure prophylaxis for syphilis or chlamydia is not endorsed by BASHH or the UK Health Security Agency (UKHSA).
• The use of other antibiotics as prophylaxis for syphilis and chlamydia, or to prevent other sexually transmitted infections (STIs), is unlikely to be effective and should be discouraged.
• If patients are taking doxycycline prophylaxis, clinicians should advise on the risks of antimicrobial resistance and the limited evidence of benefit, and should offer monitoring for adverse effects.

At the time of this statement, the evidence base was a single study in men and transgender women: the IPERGAY trial (Lancet Inf Diseases 2018;18(3):308):

• This French trial recruited 232 men who have sex with men (MSM) who were already using PrEP for HIV. The men were randomised on a 1:1 basis to a single postcoital 200mg dose of doxycycline prophylaxis or no prophylaxis within 24h of any episode of unprotected anal, vaginal or oral sex (maximum 3 doses per week) (Lancet Inf Diseases 2017;18:308). The primary endpoint was any STI. 
  • Overall, there was a 47% reduction in the relative risk of a new STI. 
  • There was no benefit shown in rates of gonorrhoea, possibly due to known high rates of doxycycline resistance in France (resistance rates 56% in France vs. 20% in the USA).  

Has the picture moved on?

In October, 2023 the Centres for Disease Control and Prevention (CDC) in the USA released draft guidance on the use of post-exposure doxycycline to prevent sexually transmitted infections (Federal Register: Guidelines for the Use of Doxycycline Post-Exposure Prophylaxis for Bacterial Sexually Transmitted Infection (STI) Prevention).

This is draft guidance at the time of writing in June 2024.

If we are prescribing doxycycline prophylaxis, also consider the following:

• Advise of potential side-effects, including skin sensitivity, GI discomfort and oesophagitis, and the risk of antibiotic resistance.
• Advise of potential drug interactions: separate dosing by at least 2 hours from antacids and other calcium-, iron- or magnesium-containing medicines or supplements.
• Advise that contraception should be used by people with reproductive potential.
• Provide enough doses of doxycycline to last until the next follow-up visit (based on a discussion with individual patients).
• Screen for gonorrhoea, chlamydia and syphilis every 3–6 months.

This draft guidance was based on evidence from two 2023 NEJM studies, and from the IPERGAY trial discussed above (NEJM 2023;388:1296, NEJM 2023;389:2331).

• DoxyPEP trial: a US trial recruited 500 MSM and transgender women taking PrEP for HIV and with a confirmed STI within the past 12 months (NEJM 2023;388:1296). They were randomised on a 2:1 basis to take 200mg doxycycline within 72h of any episode of unprotected oral, anal or vaginal sexual intercourse. The primary endpoint was incidence of STI, and the population were followed-up for 12 months.  
  • NNT 5 to prevent one STI over 3 months. 
  • There was an overall reduction in STIs by two-thirds. 
  • There were no serious adverse events. 
  • Overall rates of doxycycline-resistant Staph aureus were slightly higher in the prophylaxis group at the end of the trial, but the effect was minimal (5% compared with 4% in the no-treatment group). 
• A replication of the IPERGAY trial methods, on a population of cisgender women in Kenya, did not show the same benefit (NEJM 2023;389:2331).  
  • There were low rates of doxycycline use (44% of women did not take any doses). 
  • All the gonorrhoea found on testing was tetracycline-resistant.  
  • There is a need for further research into preventative options for STIs that are acceptable to women. 

BASHH advises (BASHH Position Statement on Doxycycline as Prophylaxis for Sexually Transmitted Infections 2021):

• Ask patients about recent use of antibiotics as prophylaxis to prevent STIs, and document which antibiotic(s) they are using and how (regimen).

Give patients the information that:

• The use of antibiotics as STI prophylaxis is not recommended in the UK because of concerns of antimicrobial resistance. Use of antibiotics in this way is off-label.
• Studies have only looked at doxycycline for prophylaxis against STIs. No other antibiotics have been tested.
• The current evidence is only in chlamydia and syphilis, not gonorrhoea, mycoplasma or viral STIs.
• Advise patients where relevant that doxycycline is not safe in pregnancy, and offer contraception if appropriate.

Prophylaxis for sexually transmitted infections There is evidence of increasing use of antibiotic prophylaxis against STIs. The evidence base is limited to small studies of MSM and transgender women. In the UK, BASHH and UKHSA guidance (2021) advises against the use of antibiotics as pre- or post-exposure prophylaxis against STIs. In the US, the CDC is consulting on plans to advise post-exposure prophylaxis with doxycycline for MSM and transgender women at increased risk of STIs. We should be alert to the fact that patients might be using antibiotics sourced elsewhere for this indication, and provide relevant information on safety if indicated.