Two years after the CDC issued its first formal clinical guidelines on doxycycline post-exposure prophylaxis, or doxyPEP, the antibiotic-based prevention strategy has moved from a promising trial result into standard practice at sexual health clinics across the country. The CDC recommends that providers discuss doxyPEP — a single 200-milligram dose of doxycycline taken within 72 hours after sex — with gay and bisexual men and transgender women who have had a bacterial STI (chlamydia, gonorrhea, or syphilis) within the past 12 months.

The recommendation rests on three large randomized controlled trials showing that the approach reduces chlamydia and syphilis infections by more than 70% and gonorrhea infections by roughly 50%. Real-world clinic data presented this year continues to bear that out: research from a large sexual health clinic in the Bronx and from a Ryan White clinic in New Orleans both reported meaningful reductions in chlamydia and gonorrhea positivity rates among patients using doxyPEP.

The strategy isn’t without debate. Public health bodies elsewhere have taken more cautious positions — Germany’s STI Society has recommended against broad rollout pending more data on antimicrobial resistance, while Australia’s HIV medicine society has endorsed doxyPEP primarily for syphilis prevention. U.S. clinicians note the most commonly cited drawback is gastrointestinal side effects, and researchers continue to monitor whether widespread doxycycline use could contribute to antibiotic resistance over time. For now, the CDC’s position remains that patients and providers should have an open, shared conversation about the benefits and unknowns before starting doxyPEP — guidance it plans to update as more data becomes available.