Potential Impact of Doxycycline Post-Exposure Prophylaxis on Tetracycline Resistance in Neisseria gonorrhoeae and Colonization with Tetracycline-Resistant Staphylococcus aureus and Group A Streptococcus.

Background: Doxycycline post-exposure prophylaxis (doxy PEP) is increasingly used among men who have sex with men (MSM). Its impact on antimicrobial resistance and the microbiome is uncertain.

Methods: We used Neisseria gonorrhoeae (NG) surveillance data from King County, WA and joinpoint regression to investigate trends in NG-tetracycline resistance (tetR), 2017-2024 and, among sexual health clinic (SHC) patients, evaluated the association of NG-tetR with doxy PEP use. We evaluated nasopharyngeal colonization with Staphylococcus aureus and Group A Streptococcus (GAS) 703 MSM SHC patients, August 2023-July 2024.

Results: Among 2,312 MSM with NG, tetR was stable 2017 to quarter 1 (Q1) 2023 (mean=27%) and thereafter rose to 70% in Q2 2024 (p<0.0001). (King County released doxy PEP guidelines in Q2 2023.) NG with high-level (HL) tetR increased Q1 2021 to Q2 2024 (2% to 65%) (p<0.0001). Taking >3 doses of doxy PEP/month was associated with both tetR and HL tetR (p≤0.01 for both), though any use of doxy PEP was not associated with tetR or HL tetR. S. aureus colonization was less common among doxy PEP users than non-users (27% vs. 36%, p=0.02), but colonization with both tetracycline-resistant S. aureus and GAS were more common among doxy PEP users than non-users (18% vs. 8%, p<0.0001 and 9% vs. 4%, p=0.008, respectively).

Conclusions: TetR in NG rapidly increased from 2021 to 2024, and most NG among King County MSM now have HL tetR. Doxy PEP use is associated with colonization with GAS and tetracycline-resistant S. aureus, suggesting that doxy PEP impacts off-target bacteria.