Denis A, Moreau N J
Centre National de la Recherche Scientifique, CERCOA, Thiais, France.
J Antimicrob Chemother. 1993 Sep;32(3):379-92. doi: 10.1093/jac/32.3.379.
The accumulation of sparfloxacin and three other fluoroquinolones of decreasing hydrophobicity, pefloxacin, ofloxacin, and ciprofloxacin, into randomly chosen fluoroquinolone-sensitive and -resistant clinical isolates of bacteria (four Enterobacteriaceae, one Pseudomonas aeruginosa and one Staphylococcus aureus) was measured. There was good correlation between the concentration of drug that inhibited early DNA synthesis in whole cells and the MIC values of the same drug regardless of organism sensitivity or the quinolone. A decrease in permeability in resistant strains compared with sensitive, due to a modification of outer membrane proteins was often involved in resistance. But, in all cases other mutations may also be involved explaining the relatively high level of resistance of the strains. In two resistant strains the DNA gyrase was purified and found to be resistant to inhibition by quinolones. The use of quinolones of differing hydrophobicity emphasized the importance of this property in the uptake of quinolones by bacterial cells, and provided evidence that sparfloxacin used both porin and the self-promoted uptake pathway for it's uptake.
测定了司帕沙星以及另外三种疏水性递减的氟喹诺酮类药物（培氟沙星、氧氟沙星和环丙沙星）在随机选择的对氟喹诺酮敏感和耐药的临床分离细菌（四种肠杆菌科细菌、一株铜绿假单胞菌和一株金黄色葡萄球菌）中的蓄积情况。无论生物体的敏感性或喹诺酮类药物如何，全细胞中抑制早期DNA合成的药物浓度与同一药物的MIC值之间存在良好的相关性。与敏感菌株相比，耐药菌株的通透性降低，这通常与外膜蛋白的修饰有关。但是，在所有情况下，其他突变也可能参与其中，这解释了菌株相对较高的耐药水平。在两株耐药菌株中，纯化了DNA回旋酶，发现其对喹诺酮类药物的抑制具有抗性。使用不同疏水性的喹诺酮类药物强调了该特性在细菌细胞摄取喹诺酮类药物中的重要性，并提供了证据表明司帕沙星通过孔蛋白和自身促进摄取途径进行摄取。
