Azithromycin Treatment Failure in Mycoplasma genitalium-Positive Patients with Nongonococcal Urethritis Is Associated with Induced Macrolide Resistance
Azithromycin Treatment Failure in Mycoplasma genitalium-Positive Patients with Nongonococcal Urethritis Is Associated with Induced Macrolide Resistance
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DOI：
10.1086/593188
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发表时间：
2008-12-15
影响因子：
11.8
通讯作者：
Hamasuna, Ryoichi
中科院分区：
文献类型：
--
作者：
Jensen, Jorgen S.;Bradshaw, Catriona S.;Hamasuna, Ryoichi
背景。生殖道支原体是引起非淋球菌性尿道炎的常见原因。治疗试验表明，多西环素无效，而5天疗程的阿奇霉素可根除95%受感染男性体内的细菌。本研究的目的是确定偶尔治疗失败的原因。从阿奇霉素治疗失败的男性中分离出7株生殖支原体菌株，采用基于细胞培养的方法检测对大环内酯类药物的体外敏感性。通过对23S核糖体RNA基因和L4、L22蛋白编码基因的部分测序，建立了耐药的遗传基础。采用聚合酶链反应产物测序法对阿奇霉素治疗失败患者治疗前后采集的9组标本进行了检测。从阿奇霉素治疗失败的患者中分离出的7株菌株对阿奇霉素和红霉素的最低抑制浓度为80 μ g/mL。在23S rRNA基因V区2058和2059位点（大肠杆菌编号）发现3个不同的突变。在治疗前后获得的9例患者标本中，只有2例患者的初始标本出现突变，提示阿奇霉素用量不当导致耐药。大环内酯类药物耐药性的发展与随后的阿奇霉素治疗失败有关。耐药的遗传基础被证明是23S rRNA基因V区突变，这在其他Mollicutes中得到了很好的描述。这些发现引起了人们对使用单剂量阿奇霉素治疗病因不明的非淋球菌性尿道炎的关注。
Background. Mycoplasma genitalium is a common cause of nongonococcal urethritis. Treatment trials have shown that doxycycline is inefficient, whereas a 5-day course of azithromycin eradicates the bacterium from 95% of infected men. The aim of the study was to establish the reason for the occasional treatment failures.Methods. Seven M. genitalium strains isolated from men who experienced azithromycin treatment failure were tested for in vitro susceptibility to macrolides with use of a cell culture-based method. The genetic basis for the drug resistance was established by sequencing parts of the 23S ribosomal RNA gene and the genes encoding the L4 and L22 proteins. Nine sets of specimens obtained before and after treatment from patients who experienced azithromycin treatment failure were examined with use of sequencing of polymerase chain reaction products.Results. The 7 strains that were isolated from patients who experienced treatment failure with azithromycin had minimum inhibitory concentrations >8 mu g/mL for azithromycin and erythromycin. Three different mutations at positions 2058 and 2059 (Escherichia coli numbering) in region V of the 23S rRNA gene were found. Of the 9 patients with specimens obtained before and after treatment, only 2 had an initial specimen in which the mutation was present, indicating that drug resistance was induced as the result of an inappropriate dosage of azithromycin.Conclusion. Development of macrolide resistance was shown to correlate with subsequent azithromycin treatment failure. The genetic basis for the drug resistance was shown to be mutations in region V of the 23S rRNA gene, which is well described in other Mollicutes. These findings raise concern about the use of single-dose azithromycin treatment of nongonococcal urethritis of unknown etiology.