Mycoplasma genitalium Susceptibility and Treatment

生殖支原体最近被认为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，该微生物与NGU独立相关，鉴于这种相关性的强度，现在确定M的有效治疗方案是适当的。生殖器相关性尿道炎虽然小规模的研究提供了一些有限的信息失败率选定的抗生素方案治疗M。生殖器感染，迄今为止，尚未进行系统的随机治疗试验。此外，虽然M.虽然已经确定了少量分离株的生殖器细菌，但这些菌株是在10-20年前收集的，因此可能不反映该细菌的当前抗菌谱。测定M. 由于该微生物的挑剔性质，使生殖器变得复杂，这使得其分离和生长（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，在本项目的目标1中，我们提出改进M.生殖器，使用我们的定量PCR测定来测量生长。通过这些改进的方法，我们将确定最近收集的临床M菌株的抗生素敏感性。生殖器在目标2中，我们将进行一项随机、双盲、安慰剂对照试验，以比较阿奇霉素和多西环素根除M的相对有效性。非淋菌性尿道炎患者的生殖器我们还将通过比较持续检测到M的患者的MIC值来描述抗生素耐药性和持续感染之间的关系。在随访时，在经历微生物学治愈的患者中检测生殖器MIC值。最后，在目标3中，一项巢式病例对照研究将比较持续性M的比例。生殖器感染的患者经历持续/复发性尿道炎症状（临床治疗失败或病例）的比例持续M。临床治愈患者的生殖器感染（对照）。我们预计，这些研究将阐明这种新兴病原体的适当治疗方案，以及进一步确定其在NGU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.