Controlling Drug Resistant Gonorrhea with Real-Time PCR Susceptibility Testing

描述（由申请人提供）：拟议的研究代表了一种控制耐药淋病奈瑟菌传播的新方法，通过使用实时聚合酶链反应（PCR）来确定个体感染的抗菌药物敏感性，并减少不必要的广谱抗生素使用。在过去的75年里，淋病对抗菌素治疗的耐药性越来越强。淋病耐药性的持续出现使许多专家指出，淋病可能成为一种无法治疗的“超级细菌”。然而，对这一严重公共卫生问题的应对仍然依赖于对治疗失败的临床警惕、伴侣治疗、维持基于文化的监测、降低风险咨询、使用避孕套、重复筛查以及呼吁开发新的抗微生物药物。使用分子测定法测定抗菌药物敏感性已成功用于治疗结核分枝杆菌和金黄色葡萄球菌感染，但尚未用于淋病。利用实时聚合酶链式反应（real-time PCR）确定抗菌素敏感性可能是一个“游戏规则改变者”，它将改变性传播疾病的治疗进程，并导致淋病耐药性的大幅减少。我们的提案有三个具体目标：1)我们将在洛杉矶县公共卫生实验室验证实时PCR分析，使其能够临床使用，并遵守联邦法规，规定在临床实践中使用实验室测试。2)会

DESCRIPTION (provided by applicant): The proposed research represents a novel approach to controlling the spread of drug-resistant Neisseria gonorrhea through the use of real-time polymerase chain reaction (PCR) 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 the real-time PCR assay in the Los Angeles County Public Health Laboratory to enable its clinical use and comply with federal regulations providing for the use of laboratory tests in clinical practice. 2) We will develop an antimicrobial susceptibility testing program that ensures that all specimens in Los Angeles County tested at the Public Health Laboratory for gonorrhea will also be tested for antimicrobial susceptibility and those results provided to the testing clinicians within two business days to use to guide antibiotic treatment. 3) We will evaluate the effect of the new assay among clinicians treating their patients with gonorrhea, including monitoring the turn-around time of susceptibility results relative to treatment, treatment selection, and surveying clinicians regarding their knowledge, attitudes, and practices regarding the molecular susceptibility results. The primary outcome of this study is the difference in the proportion of gonorrhea cases treated with an extended-spectrum cephalosporin before and after the provision of gonorrhea antimicrobial susceptibility results. Based on prior research, we hypothesize a 50% reduction in extended-spectrum cephalosporin use from 95% to 50%. Secondary outcomes will explore the association of non-extended-spectrum cephalosporin use based on both provider and case- patient characteristics. Overall, the results of this study will potentially transform the management of gonorrhea and impact the frequency of drug-resistant gonorrhea.