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目的 为研究氟喹诺酮类抗菌药物非特异性耐药机制建立细菌筛选方法,并研究其耐药特点及遗传稳定性。方法 使用高浓度四环素作诱导剂,分步诱导敏感表皮葡萄球菌产生高耐突变株,并从中选择对环丙沙星和司帕沙星耐药菌株。结果 经过4 步四环素诱导突变后,获得的突变株对四环素的M IC增加了500 倍,这些菌株中约有1/3 对环丙沙星和司帕沙星中度耐药,MIC比亲代株增加了60 倍。子代菌与亲代菌相比主要生化反应无改变,连续传代培养证明突变株对氟喹诺酮类药物的抗药性可稳定遗传。结论 采用四环素诱导突变的方法可使细菌获得对氟喹诺酮类的耐药性,提示用其它抗菌药物治疗感染失败的患者换用氟喹诺酮类药物时应慎重
Objective To study the non-specific resistance mechanism of fluoroquinolone antibacterials to establish a bacterial screening method and study its drug resistance characteristics and genetic stability. Methods High concentrations of tetracycline as inducer were used to induce the sensitive mutants of Staphylococcus epidermidis in a step-by-step manner. The resistant strains to ciprofloxacin and sparfloxacin were selected. Results After four-step tetracycline-induced mutagenesis, the obtained mutants showed a 500-fold increase in the M IC of tetracycline, about 1/3 of these strains were moderately resistant to ciprofloxacin and sparfloxacin, and MICs were more resistant than the parent strain Increased by 60 times. Compared with the parental bacteria, the offspring did not change the main biochemical reaction. The continuous subculture showed that the resistance of the mutants to fluoroquinolones could be stably inherited. Conclusion The method of tetracycline-induced mutation can make bacteria acquire resistance to fluoroquinolones, suggesting that other antibacterial drugs should be used carefully in patients with failed fluoroquinolones