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目的探讨大肠埃希菌在体外对氟喹诺酮类药物的交叉耐药性。方法采用多步诱导法,对32株临床分离的氟喹诺酮类敏感大肠埃希菌分别进行环丙沙星、左氧氟沙星、加替沙星的诱导性耐药试验;用琼脂稀释法测定药物敏感性。结果22株大肠埃希菌诱导出稳定的高耐氟喹诺酮菌株;与原株比较,耐药株的MIC分别增加了32-3 000倍,三种氟喹诺酮药物诱导的耐药株对三种药物存在交叉耐药性;进行测序的1株诱导高度耐药菌株的gyrA发生Ser83→Leu、Asp87→Asn,parC发生ser80→Ile的氨基酸替换,而测序的一株敏感菌株未发现氨基酸改变。结论在低浓度抗菌药物的长期压力下,可诱导大肠埃希菌产生对氟喹诺酮类药物的获得性耐药,氟喹诺酮药物之间存在交叉耐药性。
Objective To investigate the cross-resistance of Escherichia coli to fluoroquinolones in vitro. Methods Induction drug resistance of 32 fluoroquinolone-sensitive Escherichia coli isolates were separately induced by ciprofloxacin, levofloxacin and gatifloxacin by multi-step induction method. Drug sensitivity was determined by agar dilution method. Results 22 strains of Escherichia coli induced a stable fluoroquinolone-resistant strain. Compared with the original strain, the MICs of the resistant strains increased by 32-3 000 times respectively. The three fluoroquinolone-resistant strains showed no effect on the three drugs There was cross-resistance. The amino acid substitutions of ser80 → Ile in serrA of the highly resistant strains that were sequenced for Ser83 → Leu, Asp87 → Asn and parC occurred, but no amino acid change was found in one of the sensitive strains sequenced. Conclusions The long-term low-concentration antimicrobial drug can induce the acquired resistance to fluoroquinolones in Escherichia coli and the cross-resistance of fluoroquinolones.