Hooper D C, Wolfson J S
Medical Services, Massachusetts General Hospital, Boston 02114.
Am J Med. 1989 Dec 29;87(6C):17S-23S.
Bacterial resistance to the newer quinolones occurs less frequently than to the older analogue nalidixic acid. Single-step mutations conferring greater than eightfold increases in minimal inhibitory concentration occur at frequencies of less than 10(-10) for many bacterial species and at 10(-8) for Pseudomonas aeruginosa. Passage on increasing concentrations of quinolones, however, results in highly resistant strains of many species. Chromosomal mutations have been shown to produce two mechanisms of resistance, alterations in the A subunit of the target enzyme, DNA gyrase, and decreased drug accumulation associated with altered porin outer membrane proteins and pleiotropic resistance. For some mutants reduced accumulation appears to depend on active quinolone efflux across the inner membrane. Resistance developing during quinolone therapy of infections has been infrequent to date and reported most often with P. aeruginosa and Staphylococcus aureus, and at sites with poor quinolone penetration or foreign bodies. Resistance should be monitored, and the means for limiting its development studied.
细菌对新型喹诺酮类药物的耐药性比其对旧的类似物萘啶酸的耐药性出现得少。对于许多细菌物种，使最低抑菌浓度增加超过八倍的单步突变发生频率低于10^(-10)，而对于铜绿假单胞菌则为10^(-8)。然而，在喹诺酮类药物浓度不断增加的情况下传代培养，会导致许多物种产生高度耐药菌株。已证明染色体突变会产生两种耐药机制，即靶酶DNA回旋酶A亚基的改变，以及与孔蛋白外膜蛋白改变和多效性耐药相关的药物蓄积减少。对于一些突变体，蓄积减少似乎取决于喹诺酮类药物通过内膜的主动外排。迄今为止，在喹诺酮类药物治疗感染期间产生耐药性的情况并不常见，最常报道的是铜绿假单胞菌和金黄色葡萄球菌，以及在喹诺酮类药物穿透性差或有异物的部位。应监测耐药性，并研究限制其产生的方法。
