Mycoplasma genitalium Susceptibility and Treatment

生殖支原体最近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%。在几乎所有使用DNA扩增方法的研究中，这种细菌都与NGU独立相关，鉴于这种联系的强度，现在适合确定有效的治疗方案来治疗生殖道支原体相关性尿道炎。尽管小规模研究提供了一些关于选定抗生素方案治疗生殖道支原体感染失败率的有限信息，但到目前为止，还没有进行系统的、随机的治疗试验。此外，虽然已经确定了少数菌株对生殖支原体的抗菌活性，但这些菌株是在10-20年前收集的，因此可能不能反映这种细菌目前的抗菌谱。测定M。 生殖器由于这种微生物的挑剔性质而变得复杂，这使得它的分离和生长(抗菌素敏感性测试过程的必要组成部分)具有挑战性。因此，在本项目的目标1中，我们建议改进生殖支原体的分离和培养技术，使用我们的定量PCR方法来测量生长。利用这些改进的方法，我们将确定最近收集的生殖分枝杆菌临床菌株的抗生素敏感性。在目标2中，我们将进行一项随机、双盲、安慰剂对照试验，比较阿奇霉素和多西环素在根除非淋菌性尿道炎男性生殖道支原体方面的相对效果。我们还将通过比较持续检测生殖道支原体的患者的MIC值与经历微生物治疗的患者的MIC值来描述抗菌素耐药性与持续感染之间的关系。最后，在目标3中，一项嵌套病例对照研究将比较尿道炎持续/复发症状患者(临床治疗失败或病例)中持续生殖道支原体感染的比例与经历临床治愈的患者(对照)中持续生殖支原体感染的比例。我们预计这些研究将阐明针对这种新出现的病原体的适当治疗方案，并进一步确定其在非淋菌性尿道炎病因学中的作用。

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 non-gonococcal 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.