How do we monitor doxy-PEP impact and when should we consider revisiting guidelines?

Summary points The 2026 WHO guidelines recommending doxycycline post-exposure prophylaxis (doxy-PEP) represent the first global antibiotic prophylaxis recommendation for bacterial sexually transmitted infections (STIs), with provisions for antimicrobial resistance (AMR) monitoring. Doxy-PEP should be governed as an adaptive intervention subject to periodic, transparent review, but establishing decision rules faces challenges. Doxy-PEP is expected to select for resistance, including in Neisseria gonorrhoeae , Staphylococcus aureus, and the gut and skin microbiomes; the scope of clinical consequences is incompletely understood. As STI prevalence falls, the benefit per dose declines while the AMR externality per dose is expected to grow, shifting the cost-benefit balance in ways that vary across populations and settings. Attributing changes in disease prevalence or resistance patterns to doxy-PEP is methodologically difficult, given incompletely understood and complex drivers of pre-existing trends, surveillance limitations, and heterogeneous uptake, raising questions about study designs, data sources, eligibility criteria, and governance mechanisms. A full accounting of benefits and harms is broader than reduced bacterial STI incidence and AMR. Benefits include consideration of patient-centered outcomes such as reduced anxiety regarding STI acquisition, avoidance of repeated treatment visits, and fewer STI-related complications. Harms include drug side effects, such as gastrointestinal adverse effects and concerns about use in pregnancy.