Mycoplasma genitalium Susceptibility and Treatment

生殖支原体的易感性和治疗

• 批准号: 7962199
• 负责人: Lisa E Manhart
• 金额: $ 51.83万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7962199
• 关键词: Accounting; Antibiotic Resistance; Antibiotic susceptibility; Antibiotics; Antimicrobial Resistance; Antimicrobial susceptibility; Azithromycin; Bacteria; Biological Assay; Classification; Clindamycin; Clinic; Clinical; Clinical Treatment; County; Culture Media; DNA amplification; Detection; Doxycycline; Drug usage; Effectiveness; Etiology; Failure; Female; Growth; Infection; Macrolides; Measures; Methods; Modification; Mycoplasma; Mycoplasma genitalium; Nature; Nested Case-Control Study; Organism; Participant; Patients; Pattern; Predisposition; Process; Public Health; Quinolones; Randomized; Recurrence; Relative (related person); Reproductive Tract Infections; Research; Resistance; Role; Signs and Symptoms; Specimen; Streptogramins; Symptoms; Techniques; Testing; Tetracycline Resistance; Treatment Failure; Treatment Protocols; Universities; Upper arm; Urethritis; Visit; Washington; antimicrobial; double-blind placebo controlled trial; effective therapy; experience; follow-up; improved; male; men; novel strategies; pathogen; treatment trial

Mycoplasma genitalium has recently been implicated in both male and female reproductive tract infections and may account for up to 25% of all cases of nongonococcal urethritis (NGU). This organism was independently associated with NGU in virtually all studies using DNA amplification methods and, given the strength of this association, it is now appropriate to identify effective treatment regimens for M. genitaliumassociated urethritis. Although small-scale studies have provided some limited information on failure rates for selected antibiotic regimens treating M. genitalium infections, to date, no systematic, randomized treatment trials have been conducted. Further, although antimicrobial susceptibilities of M. genitalium have been determined for a small number of isolates, those strains were collected 10-20 years ago, and thus may not reflect the current antimicrobial profiles of this bacterium. Determining antimicrobial susceptibilities for M. genitalium is complicated by the fastidious nature of this organism, which makes its isolation and growth (necessary components of the antimicrobial susceptibility testing process) challenging. Therefore, in Aim 1 of this project, we propose to improve techniques for isolation and cultivation of M. genitalium, using our quantitative PCR assay to measure growth. With these enhanced methods, we will then determine the antibiotic susceptibility of recently collected clinical strains of M. genitalium. In Aim 2, we will conduct a randomized, double-blinded, placebo-controlled trial to compare the relative effectiveness of azithromycin and doxycycline in eradicating M. genitalium from men with NGU. We will also describe the relationship between antimicrobial resistance and persistent infection by comparing MIC values among patients with persistent detection of M. genitafium at follow-up visits to MIC values in patients who experience microbiologic cure. Finally, in Aim 3, a nested case-control study will compare the proportion of persistent M. genitalium infections among patients experiencing persistent/recurrent symptoms of urethritis (clinical treatment failures or cases) to the proportion of persistent M. genitalium infections among patients experiencing clinical cure (controls). We anticipate that these studies will elucidate the appropriate treatment regimens for this emerging pathogen, as well as further define its role in the etiology of NGU.

最近发现生殖支原体与男性和女性生殖道感染有关 可能占所有非淋菌性尿道炎 (NGU) 病例的 25%。这种生物体是 在几乎所有使用 DNA 扩增方法的研究中，与 NGU 独立相关，并且考虑到 鉴于这种关联的强度，现在应该确定针对生殖支原体相关的有效治疗方案 尿道炎。尽管小规模研究提供了一些关于失败率的有限信息 对于治疗生殖支原体感染的选定抗生素方案，迄今为止，还没有系统、随机的研究 已经进行了治疗试验。此外，尽管生殖支原体的抗菌敏感性已 已确定少数分离株，这些菌株是 10-20 年前收集的，因此可能 不反映该细菌当前的抗菌特性。确定 M 的抗菌敏感性。 生殖器由于这种生物体的挑剔性质而变得复杂，这使得它的隔离和生长 （抗菌药物敏感性测试过程的必要组成部分）具有挑战性。因此，在目标 1 在这个项目中，我们建议利用我们的技术改进生殖支原体的分离和培养技术 定量 PCR 测定来测量生长。通过这些增强的方法，我们将确定 最近收集的生殖支原体临床菌株的抗生素敏感性。在目标 2 中，我们将进行 比较阿奇霉素相对有效性的随机、双盲、安慰剂对照试验 和多西环素可根除患有 NGU 的男性生殖支原体。我们还将描述这种关系 通过比较 MIC 值来了解抗菌药物耐药性与持续感染的关系 在对以下患者的 MIC 值进行随访时持续检测到生殖支原体 微生物治疗。最后，在目标 3 中，一项巢式病例对照研究将比较持续性分枝杆菌的比例。 经历持续性/复发性尿道炎症状的患者中的生殖器感染（临床 治疗失败或病例）与患者中持续性生殖支原体感染的比例 经历临床治愈（对照）。我们预计这些研究将阐明适当的治疗方法 针对这种新兴病原体的治疗方案，并进一步明确其在 NGU 病因学中的作用。