Abstract：
Pseudomonas aeruginosa can develop resistance. Therefore, it is necessary to design proper treatment for it. Pseudomonas aeruginosa can develop resistance against levofloxacin due to the development of efflux pumps. However, the development of these efflux pumps cannot develop resistance against imipenem. Additionally, the MexCDOprJ efflux system which is responsible for the resistance of Pseudomonas aeruginosa to levofloxacin is highly susceptible to imipenem. The objective of the study was to evaluate the emergence of resistance of Pseudomonas aeruginosa against 750 mg levofloxacin, 250 mg imipenem, and a combination of 750 mg levofloxacin and 250 mg imipenem. An in vitro pharmacodynamic model was selected for the evaluation of the emergence of resistance. Pseudomonas aeruginosa strain 236, Pseudomonas aeruginosa strain GB2, and Pseudomonas aeruginosa strain GB65 were selected. Susceptibility testing of both antibiotics was done by agar dilution methodology. A disk diffusion bioassay was performed for antibiotics. RT-PCR measurement was done for the evaluation of expressions of Pseudomonas aeruginosa genes. Samples were tested at 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 24 h, and 30 h. Levofloxacin and imipenem both individually reported a decrease in colony-forming unit per milliliter of strength in the initial stage but in the later stage both develop resistance individually. Levofloxacin with imipenem had no resistance to Pseudomonas aeruginosa during 30 h. Time after the start of development of resistance or decrease in clinical efficacy was higher for levofloxacin and imipenem combination in all strains. The concentration of Pseudomonas aeruginosa at the time after the start of development of resistance or decrease in clinical efficacy was fewer for levofloxacin and imipenem combination. Levofloxacin with imipenem is recommended for the treatment of infection due to Pseudomonas aeruginosa.
摘要：
铜绿假单胞菌可产生耐药性。因此,有必要为它设计适当的治疗方法。由于外排泵的发展，铜绿假单胞菌可以对左氧氟沙星产生耐药性。然而,这些外排泵的开发不能产生对亚胺培南的抗性。此外,导致铜绿假单胞菌对左氧氟沙星耐药的MexCDOprJ外排系统对亚胺培南高度敏感。该研究的目的是评估铜绿假单胞菌对750mg左氧氟沙星的耐药性，250毫克亚胺培南，以及750毫克左氧氟沙星和250毫克亚胺培南的组合。选择体外药效学模型来评价耐药性的出现。选择铜绿假单胞菌菌株236、铜绿假单胞菌菌株GB2和铜绿假单胞菌菌株GB65。两种抗生素的敏感性测试均通过琼脂稀释方法进行。对抗生素进行圆盘扩散生物测定。进行RT-PCR测量以评估铜绿假单胞菌基因的表达。样品在2小时进行测试，4h,6h,8h,12h,16小时,24h,和30小时。左氧氟沙星和亚胺培南在初始阶段均分别报告了每毫升强度的菌落形成单位减少，但在后期均分别产生耐药性。左氧氟沙星与亚胺培南在30h内对铜绿假单胞菌没有耐药性。在所有菌株中，左氧氟沙星和亚胺培南组合开始耐药性发展或临床疗效降低后的时间较高。对于左氧氟沙星和亚胺培南组合,在开始发展耐药性或临床疗效降低之后的时间铜绿假单胞菌的浓度较少。建议将左氧氟沙星与亚胺培南用于治疗铜绿假单胞菌引起的感染。
