Schmitz F-J, Higgins P G, Mayer S, Fluit A C, Dalhoff A
Institute for Medical Microbiology and Virology, Universitätsklinikum Düsseldorf, Germany.
Eur J Clin Microbiol Infect Dis. 2002 Sep;21(9):647-59. doi: 10.1007/s10096-002-0788-z. Epub 2002 Sep 7.
The quinolones are a potent class of antimicrobial agents that target two essential enzymes of bacterial cells: DNA gyrase and topoisomerase IV. Resistance is mediated chiefly through stepwise mutations in the genes that encode these enzymes, leading to alterations of the target site. These mutations occur in an area called the "quinolone resistance determining region". In gram-positive organisms, mutations occur more often in topoisomerase IV than in DNA gyrase. This target preference appears to depend upon two factors: the species of organism and the selecting drug. Resistance can be enhanced by a decrease in intracellular drug concentration, which is mediated through efflux pumps. The newer generation of fluoroquinolones and non-fluorinated quinolones exhibits enhanced activity against gram-positive organisms compared to the older members of this drug class, although development of resistance to these drugs has been demonstrated in vitro. This review gives a chronological perspective of the literature on the action of DNA gyrase and topoisomerase IV and the mechanisms of resistance to quinolones in staphylococci, streptococci and enterococci.
喹诺酮类是一类强效抗菌剂，作用于细菌细胞的两种关键酶：DNA回旋酶和拓扑异构酶IV。耐药性主要通过编码这些酶的基因逐步突变介导，导致靶位点改变。这些突变发生在一个称为“喹诺酮耐药决定区”的区域。在革兰氏阳性菌中，拓扑异构酶IV的突变比DNA回旋酶更常见。这种对靶点的偏好似乎取决于两个因素：生物体的种类和选择的药物。细胞内药物浓度降低可增强耐药性，这是由外排泵介导的。与该药物类别的老一代药物相比，新一代氟喹诺酮类和非氟化喹诺酮类对革兰氏阳性菌的活性有所增强，尽管在体外已证明这些药物会产生耐药性。本综述按时间顺序介绍了关于DNA回旋酶和拓扑异构酶IV的作用以及葡萄球菌、链球菌和肠球菌对喹诺酮类耐药机制的文献。
