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Doxycycline post-exposure prophylaxis (Doxy-PEP) reduces bacterial sexually transmitted infections (STIs) but may select for tetracycline resistance in Neisseria gonorrhoeae and co-resistance to other antibiotics, including ceftriaxone.. The implementation of doxy-PEP should be accompanied by monitoring doxycycline resistance, but the optimal strategy to detect changes in the prevalence of resistance has not been established. We used a deterministic compartmental model of gonorrhea transmission to evaluate the performance of two strategies in providing early warning signals for rising resistance: (1) phenotypic testing of cultured isolates and (2) PCR for tetM in remnants from positive Nucleic Acid Amplification Tests (NAATs) used for gonorrhea diagnosis. For each strategy, we calculated the resistance proportion with 90% simulation intervals as well as the time under each sampling strategy to achieve 95% confidence that the resistance proportion exceeded a resistance threshold ranging from 11-30%. Given the substantially larger available sample size, PCR for tetM in remnant NAATs detected increased high-level tetracycline resistance with high confidence faster than phenotypic testing of cultured specimens. Our results suggest that population surveillance using molecular testing for tetM can complement culturebased surveillance of tetracycline resistance in N. gonorrhoeae and inform policy considerations for doxy-PEP.

Doxycycline as post-exposure prophylaxis (doxy-PEP) reduces the risk of gonorrhea, chlamydia, and syphilis in studies of men who have sex with men (MSM) and transgender women (TGW) on HIV Pre-exposure Prophylaxis (PrEP) and people living with HIV (PLWH)). Doxy-PEP is an important tool to address the increasing burden of sexually transmitted infections (STIs), but there is concern that increased consumption of doxycycline may drive antimicrobial resistance. We estimated the expected increase in antibiotic use in the US under several doxy-PEP prescribing scenarios. We accounted for doses of antibiotics that may be averted due to the prevention of chlamydia, gonorrhea, and syphilis infections by doxy-PEP. Under a scenario of 75% adoption among the eligible population, with rates of consumption similar to the DoxyPEP trial population, monthly antibiotic consumption would increase by around 2.52 million doses, driven by doxy-PEP consumption of 2.58 million doses and less 62.1 thousand antibiotic doses that would otherwise have been used for chlamydia, gonorrhea, and syphilis treatment.