(P67) Trends in Tetracycline Resistance in Neisseria gonorrhoeae as Sexually Transmitted Infection Demands for Doxycycline Increase, Gonococcal Isolate Surveillance Project (GISP), 1987 - 2022*

Background: CDC’s 2021 Sexually Transmitted Infections (STI) Treatment Guidelines highlighted the role of antimicrobial stewardship to maintain gonococcal treatment options. While doxycycline (drug class tetracycline), is no longer recommended for gonorrhea treatment, it is now the recommended regimen for chlamydia, the first step in Mycoplasma genitalium sequential treatment and the drug-of-interest for post-exposure prophylaxis in high-risk populations to reduce STIs. Given the increased doxycycline use, we reviewed US trends of Neisseria gonorrhoeae tetracycline resistance (TetR) and tetM plasmid-mediated high-level tetracycline resistance (TetHLR).

Methods: The Gonococcal Isolate Surveillance Project monitors antimicrobial susceptibility in urethral gonococcal isolates from symptomatic men at participating US STD clinics. During 1987-2022^*(^*2021-2022 data are preliminary), we determined the annual prevalence of TetR and TetHLR (minimum inhibitory concentration, MIC ≥2 µg/mL and MIC ≥16 µg/mL, respectively), stratified by sex of sex partners, and with concurrent resistance to other antimicrobials (penicillin: MIC ≥2 µg/mL or plasmid-mediated penicillinase-producing N. gonorrhoeae (PPNG); ciprofloxacin: MIC ≥1 µg/mL; ceftriaxone reduced-susceptibility: MIC ≥0.125 µg/mL).

Results: US TetR fluctuated during 1987-2022^* with a low of 14.4% in 2003 and high of 27.8% in 2019. Men having sex with men only (MSM) and men having sex with men and women (MSMW) generally demonstrated higher TetR (14.6% - 48.6% and 9.6% - 47.7%, respectively) versus men having sex with women only (MSW, 11.3% - 25.1%). TetHLR increased from 2.8% in 1987 to 14.1% in 2022^* among MSM (0.6% - 19.1%), MSMW (1.5% - 19.5%), and MSW (2.7% - 12.5%).

In 1987, isolates with TetHLR demonstrated concurrent penicillin-resistance (2.2%, 0% PPNG) and ceftriaxone reduced-susceptibility (2.2%). When doxycycline was removed from gonorrhea combination therapy in 2015, TetHLR isolates displayed concurrent penicillin-resistance (21.8%, 19.3% PPNG), ciprofloxacin-resistance (34.9%), and ceftriaxone reduced-susceptibility (0.2%). In 2022^*, isolates with TetHLR showed penicillin-resistance (48.0%, 47.7% PPNG) and ciprofloxacin-resistance (29.1%), but none demonstrated ceftriaxone reduced-susceptibility.

Conclusion: Though gonococcal TetR fluctuated, the US TetHLR prevalence generally increased. MSM and MSMW demonstrated higher levels of TetR and TetHLR than MSW. After removing doxycycline from gonorrhea treatment recommendations, TetHLR concurrent resistance with other antimicrobials remained high, with ceftriaxone as the exception. Monitoring gonococcal resistance to tetracyclines remains important as STI doxycycline demands increase.