Doxycycline Prophylaxis for Sexually Transmitted Infections

Doxycycline prophylaxis has emerged as a promising biomedical intervention to reduce the incidence of bacterial sexually transmitted infections (STIs), notably chlamydia, syphilis and gonorrhoea. Administered either before exposure (pre-exposure prophylaxis, PrEP) or after sexual contact (post-exposure prophylaxis, PEP), a single 200 mg dose of doxycycline has demonstrated efficacy in high-risk populations, particularly men who have sex with men (MSM), transgender women and people using HIV PrEP. Early trials have recorded reductions of up to two-thirds in new infections, with greatest benefit among those with recent or repeated STI diagnoses. Beyond individual protection, doxy-PEP offers potential to curb community transmission. However, widespread implementation must be balanced against the risk of selecting for resistant pathogens and perturbing the gut microbiome and commensal flora. Ongoing research addresses optimisation of prescribing strategies, durability of protection, impacts on resistance gene dynamics and feasibility in diverse global settings.

Research from Nature Portfolio

Recent work has illuminated the ecological consequences of sustained doxycycline PEP use. A six-month randomised trial in MSM and transgender women found that participants taking doxy-PEP exhibited a measurable enrichment of tetracycline resistance genes within their gut microbiome, although overall bacterial diversity remained stable. The proportional increase in both DNA-encoded and RNA-expressed resistance determinants underscores the need for surveillance of resistance gene reservoirs as prophylaxis programmes expand.

In parallel, surveillance of non-pathogenic Neisseria species in Belgium revealed that commensal organisms carry high levels of resistance to azithromycin and fluoroquinolones, with notably lower susceptibility in MSM compared to a general population cohort. These commensals pose a potential source of resistance determinants for pathogenic Neisseria gonorrhoeae, reinforcing the concept of a pan-Neisseria resistome that may be mobilised under selective pressure from prophylactic antibiotic exposure.

Doxycycline Prophylaxis for Sexually Transmitted Infections publication trend

The graph below shows the total number of articles in doxycycline prophylaxis for sexually transmitted infections across all publications each year (not limited to Nature Index journals).

Technical terms

Doxycycline post-exposure prophylaxis (doxy-PEP): Administration of a single dose of doxycycline following potential sexual exposure to prevent bacterial STI acquisition.

Gut microbiome: The community of microorganisms inhabiting the gastrointestinal tract, whose composition and function can be altered by antibiotic exposure.

Resistome: The collection of all antimicrobial resistance genes present within a microbiome, including those in dormant or commensal organisms.

Commensal Neisseria: Non-pathogenic Neisseria species colonising mucosal surfaces, which may serve as reservoirs of resistance genes transferable to pathogenic strains.

References

1. Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome. Nature Medicine (2024).
2. Effects of doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections on gonorrhoea prevalence and antimicrobial resistance among men who have sex with men in the USA: a modelling study. The Lancet Microbe (2024).
3. Antimicrobial susceptibility of commensal Neisseria in a general population and men who have sex with men in Belgium. Scientific Reports (2022).
4. Important considerations regarding the widespread use of doxycycline chemoprophylaxis against sexually transmitted infections. Journal of Antimicrobial Chemotherapy (2023).
5. Choosing New Therapies for Gonorrhoea: We Need to Consider the Impact on the Pan-Neisseria Genome. A Viewpoint. Antibiotics (2021).
6. Potential Impact of Doxycycline Post-exposure Prophylaxis Prescribing Strategies on Incidence of Bacterial Sexually Transmitted Infections. Clinical Infectious Diseases (2023).
7. Already current practice? A snapshot survey on doxycycline use for prevention of sexually transmitted infections in parts of the German MSM community. Infection (2023).