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.



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