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Controlling Drug Resistant Gonorrhea with Real-Time PCR Susceptibility Testing

通过实时 PCR 药敏测试控制耐药性淋病

基本信息

批准号：
8904588
负责人：
Jeffrey David Klausner
金额：
$ 19.51万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-15 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8904588
关键词：
Address Agar Antibiotic Therapy Antibiotics Antimicrobial Resistance Antimicrobial susceptibility Azithromycin Biological Assay Businesses California Ceftriaxone Cell Wall Centers for Disease Control and Prevention (U.S.)Cephalosporins Characteristics Ciprofloxacin Clinical Clinical Management Counseling County DNA DNA Sequence Alteration Detection Diagnosis Drug resistance Ecology Ensure Erythromycin Finland Fluoroquinolones Frequencies Gene Targeting Genetic Gonorrhea Health Health Knowledge, Attitudes, Practice Health Services Human Individual Infection Injectable Japan Laboratories Los Angeles Macrolide-resistance Maintenance Manufacturer Name Medicine Methods Minimum Inhibitory Concentration measurement Molecular Monitor Morbidity - disease rate Multi-Drug Resistance Mutation Mycobacterium tuberculosis Neisseria gonorrhoeae Nucleic Acid Amplification Tests Nucleic Acids Oral Outcome Study Patients Penicillins Performance Polymerase Chain Reaction Predisposition Proteins Protocols documentation Provider Public Health RNA amplification Recommendation Regulation Relative (related person)Research Resistance Risk Reduction Selection for Treatments Sexually Transmitted Diseases Specimen Staphylococcus aureus Streptococcal Infections Superbug Surveys Techniques Testing Tetracyclines Time Treatment Failure United States antimicrobial drug base clinical practice condoms drug development experience fluoroquinolone resistance men metropolitan molecular marker mortality novel novel strategies primary outcome programs response screening secondary outcome sex surveillance data trend vigilance

项目摘要

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.

描述（由申请人提供）：拟议的研究代表了一种通过使用实时聚合酶链反应（PCR）确定个体感染的抗菌药物敏感性并减少广谱抗生素的不必要使用来控制耐药淋病奈瑟菌传播的新方法。在过去的75年里，淋病对抗菌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对治疗失败的临床警惕、伴侣治疗、维持基于培养的监测、降低风险咨询、使用避孕套、重复筛查和呼吁开发新型抗菌药物。利用分子生物学方法测定抗生素敏感性已成功地用于治疗M。结核病和金黄色葡萄球菌感染，但还没有淋病。使用实时PCR来确定抗菌药物的敏感性可能是一个“游戏规则改变者”，改变了性传播疾病的药物治疗过程，并导致淋病耐药性的严重减少。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测定法，以使其能够临床使用，并符合联邦规定在临床实践中使用实验室检测的法规。2)我们将制定抗菌药物敏感性测试计划，确保洛杉矶县在公共卫生实验室进行淋病测试的所有标本也将进行抗菌药物敏感性测试，并在两个工作日内将测试结果提供给测试临床医生，以用于指导抗生素治疗。3)我们将评估新检测方法在治疗淋病患者的临床医生中的效果，包括监测敏感性结果相对于治疗的周转时间，治疗选择，以及调查临床医生对分子敏感性结果的知识，态度和实践。本研究的主要结果是在淋病抗菌药物敏感性结果提供之前和之后接受超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，我们假设超广谱头孢菌素的使用从95%减少到50%。次要结局将根据提供者和病例-患者特征探讨非超广谱头孢菌素使用的相关性。总的来说，这项研究的结果可能会改变淋病的管理，并影响耐药淋病的发生频率。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The Frequency of Discordant Gyrase A Genotypes Among Cases of Multiple Neisseria gonorrhoeae Infections at Different Anatomic Sites.

不同解剖部位多重淋病奈瑟菌感染病例中旋转酶 A 基因型不一致的频率。

DOI：
10.1097/olq.0000000000000912
发表时间：
2019
期刊：
Sexually transmitted diseases
影响因子：
3.1
作者：
Allan-Blitz,Lao-Tzu;Ellis,OliviaL;Bolan,Robert;Hemarajata,Peera;Humphries,RomneyM;Shahkolahi,Akbar;McGrath,Mark;Klausner,JeffreyD
通讯作者：
Klausner,JeffreyD

Wild-Type Gyrase A Genotype of Neisseria gonorrhoeae Predicts In Vitro Susceptibility to Ciprofloxacin: A Systematic Review of the Literature and Meta-Analysis.