Reviewed by Jose Lucar, MD, The George Washington University
The long-term effects of doxycycline used as post-exposure prophylaxis for sexually transmitted infections (known as Doxy PEP), including antimicrobial resistance rates, remain uncertain. While doxycycline prophylaxis has been shown to reduce the risk of chlamydia, syphilis, and, in some studies, gonorrhea in men who have sex with men and transgender women, concerns have been raised regarding the possible emergence of doxycycline resistance following the widespread use of Doxy PEP. In this study, researchers conducted in vitro experiments to assess whether resistance to doxycycline could be induced in vitro in Treponema pallidum, first by defining a sub-bactericidal concentration of doxycycline able to exert antibiotic pressure, then exposing T. pallidum to sub-bactericidal doxycycline concentrations over 7 months (both intermittently and continuously), and then performing whole-genome sequencing in T. pallidum isolates to detect mutations related to doxycycline resistance. The authors found no evidence of susceptibility changes in T. pallidum exposed to sub-bactericidal doxycycline concentrations, and no resistance mutations were detected via whole genome sequencing. While these positive findings have potential implications in the implementation of Doxy PEP, ongoing surveillance is needed.
Reference:
Tantalo LC, Luetkemeyer AF, Lieberman NAP, et al. In Vitro Exposure of Treponema pallidum to Subbactericidal Doxycycline Did Not Induce Resistance: Implications for Doxycycline Postexposure Prophylaxis. J Infect Dis. 2025;231(3):729-733. doi:10.1093/infdis/jiae381
