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

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.