The proposed research represents a novel approach to controlling the spread of drug-resistant Neisseria gonorrhoeae through the use of a multiplex real-time polymerase chain reaction (PCR) assay to determine antimicrobial susceptibility of an individual infection and reduce the unnecessary use of broad spectrum antibiotics. Over the past 75 years, gonorrhea has become increasingly resistant to antimicrobial therapy. The continued emergence of drug-resistance in gonorrhea has many experts stating that gonorrhea might become an untreatable superbug. Yet, the response to this serious public health problem continues to rely on clinical vigilance for treatment failure, partner treatment, maintenance of culture-based surveillance, risk-reduction counseling, condom use, repeat screening and calls for novel antimicrobial drug development. The use of molecular assays for antimicrobial susceptibility determination has been successfully used to treat M. tuberculosis and Staphylococcus aureus infections, but not yet with gonorrhea. The use of real-time PCR to determine antimicrobial susceptibility could be a game changer that alters the course of sexually transmitted disease medicine and leads to a critical reduction in gonorrhea drug-resistance. There are three specific aims to our proposal: 1) We will verify a real-time multiplex PCR assay in the detection of ciprofloxacin- and cefixime-susceptible NG infections in accordance with CLIA regulations. 2) We will develop a molecular antimicrobial susceptibility detection program for clinical use at a large health system and reference laboratory. 3) We will determine the impact of providing clinicians with molecular antimicrobial susceptibility results on their prescribed treatment of patients diagnosed with NG. The primary outcome of this study is the difference in the proportion of NG cases treated with injectable ceftriaxone before and after the provision of susceptibility results. Based on prior research, we hypothesize an 80% relative reduction in injectable extended-spectrum cephalosporin use from 95% to 19%. Secondary outcomes will explore the association of ciprofloxacin and cefixime use with both provider and case-patient characteristics. Overall, the study results will potentially transform the management of gonorrhea and impact the frequency of drug-resistant gonorrhea.