Fernandes P B, Hanson C W, Stamm J M, Vojtko C, Shipkowitz N L, St Martin E
J Antimicrob Chemother. 1987 Apr;19(4):449-65. doi: 10.1093/jac/19.4.449.
The frequency of development of resistance to the fluoroquinolones in vitro was generally low with Escherichia coli (in the order of 10(-7) to less than 10(-9) and high with Pseudomonas aeruginosa (in the order of 10(-5) to 10(-7)). Susceptibility to the fluoroquinolones also decreased after serial transfer in increasing concentrations of the drug. Although the MICs for the resistant E. coli variants were higher than that of the parent organism, they were still susceptible to achievable serum concentrations of all the quinolones except nalidixic acid. On the other hand some of the P. aeruginosa variants selected for resistance were resistant to achievable serum concentrations of all the quinolones. When E. coli pyelonephritis in mice was treated with the fluoroquinolones, difloxacin, A-56620, and ciprofloxacin were more effective than norfloxacin and nalidixic acid in lowering viable bacterial counts in the kidneys. The susceptibility of E. coli isolated from kidneys of mice treated with the quinolones was the same as that of the parent strain. When P. aeruginosa pyelonephritis in mice was treated with the fluoroquinolones an initial reduction in the cell count was seen, followed by an increase in the number of resistant variants. The resistant variants differed in their colony morphology and cell envelope proteins. The levels of resistance for the P. aeruginosa variants ranged from a two- to a 64-fold increase in the MIC.
大肠杆菌对氟喹诺酮类药物体外耐药的发生率通常较低（约为10^(-7)至小于10^(-9)），而铜绿假单胞菌的发生率较高（约为10^(-5)至10^(-7)）。在不断增加药物浓度的连续传代后，对氟喹诺酮类药物的敏感性也会降低。尽管耐药大肠杆菌变体的最低抑菌浓度（MIC）高于亲本菌株，但除萘啶酸外，它们对所有喹诺酮类药物可达到的血清浓度仍敏感。另一方面，一些选择出的耐药铜绿假单胞菌变体对所有喹诺酮类药物可达到的血清浓度均耐药。当用氟喹诺酮类药物治疗小鼠的大肠杆菌肾盂肾炎时，双氟沙星、A - 56620和环丙沙星在降低肾脏中活菌数量方面比诺氟沙星和萘啶酸更有效。从用喹诺酮类药物治疗的小鼠肾脏中分离出的大肠杆菌的敏感性与亲本菌株相同。当用氟喹诺酮类药物治疗小鼠的铜绿假单胞菌肾盂肾炎时，最初可见细胞数量减少，随后耐药变体数量增加。耐药变体在菌落形态和细胞包膜蛋白方面存在差异。铜绿假单胞菌变体的耐药水平在MIC上有2至64倍的增加。
