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解脲支原体中氟喹诺酮类和大环内酯类耐药相关的突变。

Fluoroquinolone and macrolide resistance-associated mutations in Mycoplasma genitalium.

机构信息

Department of Biological Sciences, Macquarie University, North Ryde, NSW, Australia.

出版信息

J Clin Microbiol. 2013 Jul;51(7):2245-9. doi: 10.1128/JCM.00495-13. Epub 2013 May 8.

Abstract

Mycoplasma genitalium is a significant sexually transmitted pathogen, causing up to 25% of cases of nongonococcal urethritis in men, and it is strongly associated with cervicitis and pelvic inflammatory disease in women. Currently, the usual first-line treatment is the macrolide antibiotic azithromycin, but an increasing incidence of treatment failure over the last 5 years suggests the emergence of antibiotic resistance. The mutations responsible for macrolide resistance have been found in the 23S rRNA gene in numerous M. genitalium populations. A second-line antibiotic, the fluoroquinolone moxifloxacin, was thought to be a reliable alternative when azithromycin began to fail, but recent studies have identified mutations that may confer fluoroquinolone resistance in the genes parC and gyrA. The aim of this study was to determine the prevalence of antibiotic resistance in M. genitalium in Sydney, Australia, by detecting relevant mutations in the 23S rRNA gene, parC, and gyrA. M. genitalium-positive DNA extracts of specimens, collected from patients attending sexual health clinics in Sydney, were tested by PCR amplification and DNA sequence alignment. The 186 specimens tested included 143 initial patient specimens and 43 second, or subsequent, specimens from 24 patients. We identified known macrolide resistance-associated mutations in the 23S rRNA gene in 43% of the initial patient samples and mutations potentially associated with fluoroquinolone resistance in parC or gyrA sequences in 15% of the initial patient samples. These findings support anecdotal clinical reports of azithromycin and moxifloxacin treatment failures in Sydney. Our results indicate that further surveillance is needed, and testing and treatment protocols for M. genitalium infections may need to be reviewed.

摘要

生殖支原体是一种重要的性传播病原体,可导致男性非淋菌性尿道炎的 25%,并且与女性宫颈炎和盆腔炎密切相关。目前,通常的一线治疗药物是大环内酯类抗生素阿奇霉素,但在过去 5 年中,治疗失败的发生率不断增加,表明出现了抗生素耐药性。在许多生殖支原体群体中,23S rRNA 基因中的突变与大环内酯类耐药有关。当阿奇霉素开始失效时,二线抗生素氟喹诺酮类莫西沙星被认为是一种可靠的替代品,但最近的研究发现,在 parC 和 gyrA 基因中可能存在赋予氟喹诺酮类耐药性的突变。本研究旨在通过检测 23S rRNA 基因、parC 和 gyrA 中的相关突变,确定澳大利亚悉尼生殖支原体的抗生素耐药性流行情况。从悉尼性健康诊所就诊的患者采集的生殖支原体阳性 DNA 提取物通过 PCR 扩增和 DNA 序列比对进行检测。在 186 个测试标本中,包括 143 个初始患者标本和 24 个患者的 43 个后续标本。我们在 43%的初始患者样本中发现了 23S rRNA 基因中与大环内酯类耐药相关的已知突变,在 15%的初始患者样本中发现了 parC 或 gyrA 序列中可能与氟喹诺酮类耐药相关的突变。这些发现支持了在悉尼临床报告中关于阿奇霉素和莫西沙星治疗失败的传闻。我们的研究结果表明需要进一步监测,生殖支原体感染的检测和治疗方案可能需要重新评估。

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