汉赛巴尔通体红霉素体外诱导耐药研究

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摘要目的体外诱导汉赛巴尔通体对红霉素的耐药菌株,初步探索其耐药的发生规律。方法选取对红霉素均敏感的汉赛巴尔通体参考株Houston-1（ATCC 49882）和6株国内猫分离株作为出发菌株。出发菌株连续培养3代后开始诱导,红霉素起始浓度为出发菌株初始MIC的1/4,逐级倍增诱导浓度,直至菌株停止生长或诱导成高度耐药菌株。采用E-test法和琼脂稀释法测定耐药前后试验菌株对红霉素和其他10种抗生素的最低抑菌浓度（minimal inhibition concentrations,MICs）。同时测定出发菌株无药传代后菌株的MICs值。结果经过12代诱导,6株菌除获得对红霉素耐药（MIC值>256 µg/mL）外,对阿奇霉素和克林霉素也差生耐药,MIC值>256 µg/mL。出发菌株自然传代30次后,有4株菌对克林霉素产生了一定的耐药,对其他抗生素耐药情况没有变化。结论通过体外浓度递增法首次成功诱导汉赛巴尔通体对红霉素耐药,并产生对同系药物阿奇霉素的耐药和林克酰胺类克林霉素的耐药,提供了苛养、包内寄生菌耐药菌株模型,为今后进一步研究巴尔通体对大环内脂类抗生素的相关耐药机制奠定了基础。

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关键词 ：汉赛巴尔通体, 红霉素, 诱导耐药, 最低抑菌浓度, 猫抓病

Abstract：[Objective] Erythromycin has been often used to treat Bartonella-associated infections. Our aim here was to induction of erythromycin resistant in B. henselae. [Methods] The reference strain Houston-1（ATCC 49882）and the six wild strains were selected as the candidates for the induction of erythromycin resistant, which were all susceptible to erythromycin. The original strains, which were subcultured three passages after recovery were used to induce drug resistance. The initiative concentration of erythromycin was 1/4 × MIC. In vitro induction was carried out on serial doubling concentrations of antibiotics incorporated into agar.MICs for erythromycin and the other antibiotics were determined using the agar dilution and E-test methods. The blank control of B. henselae strain was measured MICs for detecting whether subcultrues have an effect on the development of resistance. [Results] After 12 passages on antibiotics plates, six strains acquired resistance to erythromycin and azithromycin with MICs > 256 mg/L. The six erythromycin-resistant mutants also displayed resistant to clindamycin. All were sensitive to other antibiotics. After 30 passages on plates, four strains had a certain level of resistance to clindamycin,the others had not changed. [Conclusion] Bartonella henselae can be induced to be resistant to erythromycin and azithromycin in vitro by increasing drug concentration serially and the acquired erythromycin-resistant strains were resistant to clindamycin. The study provided a model of fastidious, facultative intracellular bacilli for the further study of mechanism of Bartonella resistance to macrolides.

Key words： Bartonella henselae Erythromycin Induction of resistance MICs Cat scratch disease

基金资助:国家自然科学基金(No.81101286)

通讯作者: ^* 通讯作者：栗冬梅,E-mail: lidongmei@icdc. cn

作者简介: 宋秀平,女,1972.6.5,副主任技师,硕士,主要从事巴尔通体病原学及分子生物学研究,songxiuping@icdc.cn

引用本文:

宋秀平,刘起勇,刘云彦,栗冬梅. 汉赛巴尔通体红霉素体外诱导耐药研究[J]. 实用预防医学, 2015, 22(6): 645-647. SONG Xiu-Ping, LIU Qi-Yong, LI Dong-Mei. In Vitro Induction of Erythromycin Resistant in Bartonella henselae. , 2015, 22(6): 645-647.

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https://www.syyfyx.com/CN/ 或 https://www.syyfyx.com/CN/Y2015/V22/I6/645

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