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喹诺酮类药物是一类以1,4-二氢-4-氧- 3喹啉羧酸为基本结构的化学合成类抗菌药物.因具抗菌谱广、抗菌活性强、胞内渗透力强及不良反应少等特点,故得以迅速发展,近十年一系列新合成药物相继问世.然而,随着临床的广泛应用,其耐药菌株尤其是耐药葡萄球菌明显增加.1987年上海地区临床分离的甲氧西林耐药金葡菌(MRSA)对氟喹诺酮药物的敏感率为98.l%,而1992年其耐药率已上升至45%～66%.近年来,国内外对其耐药机制进行了大量研究,发现金葡菌对喹诺酮药物的耐药机制包括以下四个方面:(1)GyrA的改变导致喹诺酮药物抑制DNA旋转酶的活性降低,金葡菌GyrA上的点突变与大肠杆菌的点突变极相似;(2)norA介导的膜蛋白黄花系统改变,通过该机制使细菌对诺氟沙星、氧氟沙星及环丙沙星等亲水性药物的耐药性高于司帕沙星等疏水性药物;(3)cfxB-ofxC(flqA)可引起金葡菌对喹诺酮类药物耐药,此机制目前尚不清楚;(4)GyrB上的点突变与喹诺酮耐药亦有关.本文对上述耐药机制作一综述.
Quinolones are a class of chemical synthesis antibacterial drugs with the basic structure of 1,4-dihydro-4-oxo-3-quinolinecarboxylic acid. Due to its broad antibacterial spectrum, strong antibacterial activity, strong intracellular infiltration and poor Less response and so on, it has been able to develop rapidly in the past decade a series of new synthetic drugs have come out.However, with the widespread use of clinical and drug-resistant strains, especially drug-resistant Staphylococcus significantly increased in 1987 in Shanghai clinical isolation The sensitivity rate of methicillin-resistant Staphylococcus aureus (MRSA) to fluoroquinolones was 98.1%, but its resistance rate had risen to 45% -66% in 1992. In recent years, A large number of studies have shown that S. aureus quinolone resistance mechanisms include the following four aspects: (1) changes in GyrA lead to quinolone inhibition of DNA gyrase activity decreased, Staphylococcus aureus GyrA point mutations and E. coli (2) norA mediated membrane protein yellow flower system changes, by the mechanism of bacteria to norfloxacin, ofloxacin and ciprofloxacin and other hydrophilic drug resistance is higher than Sparfloxacin and other hydrophobic drugs; (3) cfxB-ofxC (flqA) can cause Staphylococcus aureus quinolone Drug resistance, this mechanism is not clear; point mutation on (4) GyrB and quinolone-resistant paper production is also related to a review of the above-mentioned resistance machines.