PROJECT SUMMARY Antimicrobial resistant (AMR) Neisseria gonorrhoeae (NG) is an urgent public health threat according to the Centers for Disease Control and Prevention (CDC).1 The gonococcus has developed resistance to all recommended treatment regimens since the 1930s. Recently, resistance to azithromycin (AZM), one of two drugs used in combination to treat gonorrhea, has increased rapidly, particularly among men who have sex with men (MSM).2 According to CDC surveillance data, heterosexual male urethral NG harbored AZM resistance in 2.4% of cases, whereas MSM urethral NG with AZM-resistance was ~3.5 times higher (8.2%).3 Exposure to antibiotics leads to antibiotic resistance. At present, AZM is part of CDC recommended treatment regimens for both NG and chlamydia (CT). MSM are disproportionately infected with these sexually transmitted infections (STI). Given high rates of infection, high numbers of sexual partners in dense sexual networks, many MSM receive AZM, a drug used for both NG and CT, either for treatment of known infection or empirically, for possible exposures to these infections from an infected sex partner, prior to the results of their test. This is a public health practice known as epidemiologic treatment, or “Epi-Tx”. 1,2 The strategy was developed at a time when diagnostic tests were suboptimal, and antibiotics were in abundance. However, Epi-Tx has not been examined in the current era where we have improved STI diagnostics, yet a waning antimicrobial developmental pipeline, and there is little-to-no data on the use of Epi-Tx in MSM, nor the role that Epi-Tx plays in the development of AMR NG. The overarching goal of this proposal is to 1) quantify the annual use of Epi-Tx among MSM at an urban STI Clinic; 2) determine the extent to which AZM use, broadly, and Epi-Tx, in particular, play in the development of AZM- resistant gonorrhea and 3) to create a risk prediction score to determine clinical, social and behavioral determinants to predict which MSM should receive Epi-Tx at a clinic visit and which should wait for test results. Understanding the incidence of Epi-Tx among STD clinic attending MSM, the extent of unnecessary antibiotic exposure related to this intervention, and its impact on the development of AZM-resistant NG, are the first steps to defining the problem. Identifying predictors of positive NG/CT tests for those receiving Epi-Tx will help limit MSM's exposure to unnecessary antibiotics. Together, the data generated from this proposal will help inform the CDC's antibiotic prescribing policies for bacterial STDs which has the potential to prevent the further development of antimicrobial resistant, not only in N. gonorrhoeae, but in other bacteria as well.