A Prospective Cohort Study to Determine Optimal Timing of Test of Cure for Pharyngeal Gonorrhea with NAAT

确定 NAAT 治疗咽部淋病最佳时机的前瞻性队列研究

• 批准号: 9583290
• 负责人: Lindley Barbee
• 金额: $ 7.77万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-20 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9583290
• 关键词: Aftercare; Anatomy; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Azithromycin; Bacteria; Behavioral; Biological; Body mass index; Ceftriaxone; Centers for Disease Control and Prevention (U.S.); Chlamydia; Clinical; Clinical Trials; Clinical Trials Design; Data; Detection; Development; Diagnosis; Diagnostic; Effectiveness; Enrollment; Epidemic; Exposure to; Future; Genetic Materials; Gonococcal urethritis; Gonorrhea; Home environment; Incubators; Infection; Laboratories; Microbiology; Modality; Neisseria; Neisseria gonorrhoeae; Nucleic Acid Amplification Tests; Oral Sex; Organism; Participant; Pharmaceutical Preparations; Pharyngeal structure; Play; Population; Positive Test Result; Process; Prospective cohort study; Public Health; Public Health Practice; RNA; Recommendation; Regimen; Research Personnel; Resistance; Resistance development; Role; STI prevention; Selection Bias; Sex Behavior; Social Behavior; Solid; Source; Specimen; Swab; Testing; Time; Treatment Efficacy; Treatment Failure; Treatment Protocols; Treatment outcome; Trust; antimicrobial; azithromycin resistance; clinical practice; co-infection; design; hazard; improved; men who have sex with men; microbial; microorganism; mutant; novel therapeutics; prospective; public health research; standard of care; study population; tool; transmission process; treatment guidelines; treatment trial

PROJECT SUMMARY Neisseria gonorrhoeae, the causative agent of gonorrhea, has developed resistance to every first-line antibiotic since the 1930s, earning it a reputation as the third most important antimicrobial resistant organism.1 Azithromycin-resistance has recently emerged, threatening the CDC’s only recommended treatment regimen – ceftriaxone plus azithromycin – and there are few new drugs in the pipeline. Gonorrhea of the throat is important not only for its role in transmission, but also in its role in the development of antibiotic resistance. Thus, all new drugs to treat gonorrhea should be evaluated for their efficacy in treating pharyngeal gonorrhea. Moreover, public health control of resistant gonorrhea relies on assurance that the bacteria have been eradicated. Unfortunately a key piece of data to evaluate treatment efficacy at the throat is missing– when can you reliably trust test of cure by nucleic acid amplification test (NAAT)? NAAT have largely replace culture for diagnosing gonorrhea because they are more sensitive, and easier and quicker to process in the laboratory compared to culture. However, since NAAT detect both viable and non-viable organisms, a positive test result, particularly shortly following treatment, may represent a false-positive. To resolve this unanswered question, we propose a prospective trial of MSM who will swab their throat daily at-home for 21 days using Aptima Combo 2 NAAT following treatment with the standard of care regimen, ceftriaxone and azithromycin. We aim to: 1) Determine the number of days following treatment when Aptima Combo 2 becomes negative for gonorrhea detection for the median and >95% of study population and 2) Identify biologic, microbiologic and socio-behavioral factors associated with time to clearance. We will collect clinical, behavioral and microbiologic data to associate factors with longer times to clearance. Using Kaplan-Meier curves we will determine when the median and >95% of the study population’s NAAT clear, using a strict definition of at least two consecutive negative NAAT. We will use Cox proportional hazards to evaluate biologic and socio-behavioral factors associated with time to clearance. We hypothesize that NAAT clearance will occur at 10 days for >95% of the study population; that higher body mass index, elevated ceftriaxone and/or azithromycin minimal inhibitory concentrations (MIC), chlamydial co-infection at the pharynx and resumption of sexual activity < 7 days after treatment will require more days to clear; and that subjects with ≥1 episodes of gonorrhea in the last year will have fewer days of NAAT positivity. The proposed prospective cohort study will provide robust and specific evidence for when to perform a test of cure for gonorrhea at the most difficult to treat anatomic site – the pharynx. This data will aid researchers in designing new antibiotic treatment trials which are urgently needed and must include efficacy data for pharyngeal infections. Additionally, this evidence will immediately inform the CDC STD Treatment Guidelines recommendations and provide another tool to control the gonorrhea epidemic.

项目摘要 淋病奈瑟氏菌是淋病的病原体，对每一种一线抗生素都产生了耐药性 自20世纪30年代以来，它赢得了作为第三大最重要的抗微生物耐药生物的声誉。 阿奇霉素耐药性最近出现，威胁到CDC唯一推荐的治疗方案- 头孢曲松加阿奇霉素--而且几乎没有新药在研发中。喉咙淋病是 这不仅因为它在传播中的作用，而且因为它在抗生素耐药性的发展中的作用。 因此，所有治疗淋病的新药都应评估其治疗咽部淋病的疗效。 此外，对耐药性淋病的公共卫生控制依赖于确保细菌已被 被消灭了不幸的是，评估喉部治疗效果的一个关键数据缺失--什么时候可以 您是否可靠地信任核酸扩增测试（NAAT）的治愈测试？NAAT在很大程度上取代了文化， 诊断淋病，因为它们更敏感，更容易和更快地在实验室处理 与文化相比。然而，由于NAAT可以检测到活的和非活的微生物，因此阳性检测结果， 特别是在治疗后不久，可能代表假阳性。为了解决这个悬而未决的问题， 我们提出了一项前瞻性试验的男男性接触者将拭子他们的喉咙每天在家里21天使用Aptima 标准治疗方案、头孢曲松和阿奇霉素治疗后的Combo 2 NAAT。我们的目标 至：1）确定治疗后Aptima Combo 2对以下各项呈阴性的天数： 淋病检测的中位数和>95%的研究人群和2）确定生物，微生物和 与清除时间相关的社会行为因素。我们将收集临床，行为和微生物 数据，以将因素与更长的清除时间联系起来。使用Kaplan-Meier曲线，我们将确定何时 中位数和>95%的研究人群的NAAT明确，使用至少两个连续的严格定义， NAAT阴性。我们将使用考克斯比例风险来评估生物和社会行为因素 与通关时间有关我们假设NAAT清除将发生在10天的>95%的 研究人群：体重指数越高，头孢曲松和/或阿奇霉素最小抑制 浓度（MIC），咽部衣原体共感染和性活动恢复后< 7天 治疗将需要更多的时间来清除;并且在过去一年中有≥1次淋病发作的受试者将 NAAT阳性的天数更少。拟议的前瞻性队列研究将提供稳健和具体的 什么时候在最难治疗的解剖部位进行淋病治愈测试的证据- 咽这些数据将有助于研究人员设计迫切需要的新抗生素治疗试验 并且必须包括咽部感染的疗效数据。此外，这一证据将立即通知 疾病预防控制中心性病治疗指南的建议，并提供另一种工具，以控制淋病的流行。