Controlling Drug Resistant Gonorrhea with Real-Time PCR Susceptibility Testing

描述(申请人提供)：这项拟议的研究代表了一种新的方法，通过使用实时聚合酶链式反应(PCR)来确定个体感染的抗菌素敏感性，并减少不必要的广谱抗生素的使用，来控制耐药淋病的传播。在过去的75年里，淋病对抗菌治疗的抗药性越来越强。淋病的耐药性不断出现，许多专家表示，淋病可能成为无法治愈的“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临床对治疗失败的警惕、合作伙伴治疗、保持以文化为基础的监测、降低风险咨询、避孕套使用、重复筛查和呼吁开发新的抗微生物药物。分子药敏试验已经成功地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。使用实时聚合酶链式反应来确定抗菌素的敏感性可能会改变性传播疾病药物的进程，并导致淋病耐药性的严重降低。我们的建议有三个具体目标：1)我们将在洛杉矶县公共卫生实验室验证实时PCR检测，以使其能够临床使用，并遵守联邦法规，规定在临床实践中使用实验室检测。2)我们会 制定抗菌素敏感性测试计划，以确保洛杉矶县所有在公共卫生实验室进行淋病测试的标本也将接受抗菌素敏感性测试，并在两个工作日内将测试结果提供给检测临床医生，以用于指导抗生素治疗。3)我们将在治疗淋病患者的临床医生中评估新的检测方法的效果，包括监测药敏结果相对于治疗、治疗选择的周转时间，以及调查临床医生对分子药敏结果的知识、态度和做法。这项研究的主要结果是在提供淋病药物敏感性结果之前和之后使用广谱头孢菌素治疗的淋病病例比例的差异。基于先前的研究，我们假设广谱头孢菌素的使用量将从95%减少到50%。次要结果将探索基于提供者和病例-患者特征的非广谱头孢菌素使用之间的关联。总体而言，这项研究的结果可能会改变淋病的管理，并影响耐药淋病的频率。

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.