Reducing excess broad-spectrum antibiotic use in gonorrhea

减少淋病中过量使用广谱抗生素

• 批准号: 9263889
• 负责人: Jeffrey David Klausner
• 金额: $ 23.1万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-19 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9263889
• 关键词: Address; Agar; Alleles; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Antimicrobial susceptibility; Azithromycin; Biological Assay; California; Cefixime; Ceftriaxone; Cell Wall; Centers for Disease Control and Prevention (U.S.); Cephalosporin Resistance; Cephalosporins; Characteristics; Ciprofloxacin; Clinical; Clinical Management; Counseling; DNA Sequence Alteration; Data; Detection; Diagnosis; Doxycycline; Drug resistance; Drug-resistant Neisseria Gonorrhoeae; Ecology; Enzymes; Erythromycin; Evolution; Finland; Fluoroquinolones; Frequencies; Genes; Genetic; Gonorrhea; Health system; Human; Individual; Infection; Injectable; Japan; Laboratories; Macrolide-resistance; Maintenance; Manufacturer Name; Medicine; Methods; Minimum Inhibitory Concentration measurement; Modernization; Molecular; Morbidity - disease rate; Mosaicism; Multi-Drug Resistance; Mutation; Mycobacterium tuberculosis; Neisseria gonorrhoeae; Nucleic Acid Amplification Tests; Oral; Outcome Study; Patients; Penicillins; Performance; Pharmaceutical Preparations; Phenotype; Play; Polymerase Chain Reaction; Predisposition; Protocols documentation; Provider; Public Health; Recommendation; Regulation; Research; Resistance; Risk Reduction; Role; Sexually Transmitted Diseases; South African; Specimen; Staphylococcus aureus; Streptococcal Infections; Superbug; Techniques; Testing; Tetracyclines; Time; Treatment Failure; United States; antimicrobial drug; base; condoms; disorder prevention; drug development; drug-resistant gonorrhea; efflux pump; experience; men who have sex with men; molecular marker; mortality; novel; novel strategies; personalized approach; primary outcome; programs; public health relevance; response; screening; secondary outcome; surveillance data; vigilance

 DESCRIPTION (provided by applicant): 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.

 描述（由申请人提供）：拟定研究代表了一种通过使用多重实时聚合酶链反应（PCR）测定来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）我们将根据CLIA法规验证实时多重PCR检测环丙沙星和头孢肟敏感NG感染的方法。2)我们将开发一个分子抗菌药物敏感性检测程序，供大型卫生系统和参考实验室临床使用。3)我们将确定向临床医生提供分子抗菌药物敏感性结果对 他们对诊断为NG的患者的处方治疗。本研究的主要结局是提供药敏结果前后接受注射用头孢曲松治疗的NG病例比例的差异。基于先前的研究，我们假设注射用超广谱头孢菌素的使用从95%相对减少80%到19%。次要结果将探讨环丙沙星和头孢克肟的使用与供应商和病例-患者特征的关联。总的来说，研究结果可能会改变淋病的管理，并影响耐药淋病的频率。

项目成果

Real-Time PCR Targeting the penA Mosaic XXXIV Type for Prediction of Extended-Spectrum-Cephalosporin Susceptibility in Clinical Neisseria gonorrhoeae Isolates.

针对 penA Mosaic XXXIV 型的实时 PCR 预测临床淋病奈瑟菌分离株中的超广谱头孢菌素敏感性。

• DOI: 10.1128/aac.01339-17
• 发表时间: 2017
• 期刊: Antimicrobial agents and chemotherapy
• 影响因子: 4.9
• 作者: Wong,LK;Hemarajata,P;Soge,OO;Humphries,RM;Klausner,JD
• 通讯作者: Klausner,JD

A multisite implementation of a real-time polymerase chain reaction assay to predict ciprofloxacin susceptibility in Neisseria gonorrhoeae.

多位点实施实时聚合酶链式反应测定，以预测淋病奈瑟菌对环丙沙星的敏感性。

• DOI: 10.1016/j.diagmicrobio.2018.12.018
• 发表时间: 2019
• 期刊: Diagnostic microbiology and infectious disease
• 影响因子: 2.9
• 作者: Ellis,Olivia;Hemarajata,Peera;Shahkolahi,Akbar;Masinde,Godfred;Buchs,Kerry;Humphries,RomneyM;Klausner,JeffreyD
• 通讯作者: Klausner,JeffreyD