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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 mg/L)外,对阿奇霉素和克林霉素也产生耐药(MIC值>256 mg/L)。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。
OBJECTIVE To induce erythromycin-resistant strains of Bartonella hensei in vitro and to explore the regularity of drug resistance. Methods Susceptible strains of erythromycin were selected from Houstonstreet-1 (ATCC 49882) and 6 domestic cat isolates as starting strains. After 3 generations of starting strain, the starting strain began to induce. The initial concentration of erythromycin was 1/4 of the initial MIC of the starting strain, and the concentration was gradually increased until the strain stopped growing or was induced into a highly resistant strain. The minimum inhibitory concentrations (MICs) of erythromycin and 10 other antibiotics were tested by E-test and agar dilution before and after drug resistance. At the same time, the MICs of the starting strains after drugless passage were determined. Results After 12 generations of induction, six strains were also resistant to azithromycin and clindamycin (MIC> 256 mg / L), except that they were resistant to erythromycin (MIC> 256 mg / L). After the initial passage of the original strain 30 times, 4 strains of clindamycin had some resistance, no change in the other antibiotic resistance. CONCLUSIONS: The first time, in vitro concentration-increasing method was successfully used to induce resistance of Erythroculter Bartleyella to erythromycin and to produce resistance to azithromycin and clindamycin resistance of homocysteine, Bacterial drug-resistant strain model for the future further study of Bartonella macrolide antibiotics related mechanisms of resistance laid the foundation.