Kojima T, Inoue M, Mitsuhashi S
Episome Institute, Gunma, Japan.
Antimicrob Agents Chemother. 1989 Nov;33(11):1980-8. doi: 10.1128/AAC.33.11.1980.
The activity of AT-4140, a new fluoroquinolone, was evaluated against a wide range of clinical bacterial isolates and compared with those of existing analogs. AT-4140 had a broad spectrum and a potent activity against gram-positive and -negative bacteria, including Legionella spp. and Bacteroides fragilis. The activity of AT-4140 against gram-positive and -negative cocci, including Acinetobacter calcoaceticus, was higher than those of ciprofloxacin, ofloxacin, and norfloxacin. Its activity against gram-negative rods was generally comparable to that of ciprofloxacin. Some isolates of methicillin-resistant Staphylococcus aureus (MIC of methicillin, greater than or equal to 12.5 micrograms/ml) were resistant to existing quinolones, but many of them were still susceptible to AT-4140 at concentrations below 0.39 micrograms/ml. The MICs of AT-4140, ciprofloxacin, ofloxacin, and norfloxacin for 90% of clinical isolates of methicillin-resistant S. aureus were 0.2, 12.5, 6.25, and 100 micrograms/ml, respectively. AT-4140 was bactericidal for each of 20 clinical isolates of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Pseudomonas aeruginosa at concentrations near the MICs. AT-4140 inhibited the supercoiling activity of DNA gyrase from E. coli.
对新型氟喹诺酮类药物AT - 4140针对多种临床分离细菌的活性进行了评估，并与现有类似药物进行了比较。AT - 4140具有广谱抗菌活性，对革兰氏阳性菌和阴性菌均有强效作用，包括嗜肺军团菌属和脆弱拟杆菌。AT - 4140对革兰氏阳性和阴性球菌（包括乙酸钙不动杆菌）的活性高于环丙沙星、氧氟沙星和诺氟沙星。其对革兰氏阴性杆菌的活性一般与环丙沙星相当。一些耐甲氧西林金黄色葡萄球菌分离株（甲氧西林MIC≥12.5微克/毫升）对现有喹诺酮类药物耐药，但其中许多在浓度低于0.39微克/毫升时仍对AT - 4140敏感。AT - 4140、环丙沙星、氧氟沙星和诺氟沙星对90%耐甲氧西林金黄色葡萄球菌临床分离株的MIC分别为0.2、12.5、6.25和100微克/毫升。在接近MIC的浓度下，AT - 4140对20株金黄色葡萄球菌、大肠埃希菌、肺炎克雷伯菌、粘质沙雷菌和铜绿假单胞菌的临床分离株均具有杀菌作用。AT - 4140抑制了大肠杆菌DNA回旋酶的超螺旋活性。
