As doxycycline post-exposure prophylaxis (doxyPEP) becomes more widely used to prevent sexually transmitted infections, questions remain about its impact on drug resistance. Taking a single dose of the antibiotic within 72 hours after sex dramatically lowers the risk for chlamydia and syphilis, with a more modest effect on gonorrhea. A pivotal trial did not show a marked increase in antimicrobial resistance, but a recent report in The New England Journal of Medicine raises concerns. An analysis of more than 14,000 Neisseria gonorrhoeae genome sequences found that the proportion carrying tetM, a gene that confers tetracycline resistance, rose from less than 10% in 2020 to over 30% in early 2024, coinciding with growing use of doxyPEP. Nonetheless, experts at the IAS Conference on HIV Science said that doxyPEP is an appropriate option for some people, with the benefits outweighing potential harms. While doxyPEP is highly effective for preventing chlamydia and syphilis, they agreed that better approaches are needed for gonorrhea.