Morissey I, Smith J T
Department of Pharmaceutics, School of Pharmacy, University of London, UK.
Arzneimittelforschung. 1994 Oct;44(10):1157-61.
The minimum inhibitory concentrations (MICs), bactericidal activities and mechanisms of action of ofloxacin (CAS 82419-36-1), levofloxacin (CAS 100986-85-4) and ciprofloxacin (CAS 86393-32-0) were investigated against Pseudomonas aeruginosa. All three 4-quinolones were found to possess higher MICs against Pseudomonas aeruginosa than against other Gram-negative bacteria. Despite this, however, all three drugs were more rapidly bactericidal and produced a greater level of kill against Pseudomonas aeruginosa than against any other bacterial species previously tested. Thus MIC tests cannot be used to predict the bactericidal activity of 4-quinolones. Furthermore, MIC tests showed ciprofloxacin to be more potent than ofloxacin or levofloxacin against Pseudomonas aeruginosa. However, bactericidal tests showed levofloxacin to be about 10 times more bactericidal than either ciprofloxacin or ofloxacin. Thus MIC tests cannot predict the relative bactericidal potency of 4-quinolones against Pseudomonas aeruginosa. Therefore, MIC tests should not be used as the sole measure for the efficacy of 4-quinolones, as is often the case. Surprisingly, the characteristic biphasic dose response curve, normally shown by 4-quinolones against other bacteria, was absent when Pseudomonas aeruginosa was tested. This unusual effect was explained by the presence of bactericidal mechanism B associated with the unique loss of bactericidal mechanism A at high 4-quinolone concentrations. This loss of bactericidal mechanism A may explain the recent high incidences of chromosomally-mediated 4-quinolone resistance with Pseudomonas aeruginosa because it may be easier for Pseudomonas aeruginosa to mutate to resist one mechanism of action than to mutate to resist two or more mechanisms of action.
研究了氧氟沙星（CAS 82419 - 36 - 1）、左氧氟沙星（CAS 100986 - 85 - 4）和环丙沙星（CAS 86393 - 32 - 0）对铜绿假单胞菌的最低抑菌浓度（MICs）、杀菌活性及作用机制。发现这三种4 - 喹诺酮类药物对铜绿假单胞菌的MICs高于对其他革兰氏阴性菌的MICs。然而，尽管如此，这三种药物对铜绿假单胞菌的杀菌速度更快，且杀菌水平高于之前测试的任何其他细菌种类。因此，MIC测试不能用于预测4 - 喹诺酮类药物的杀菌活性。此外，MIC测试表明环丙沙星对铜绿假单胞菌的效力高于氧氟沙星或左氧氟沙星。然而，杀菌测试表明左氧氟沙星的杀菌能力比环丙沙星或氧氟沙星强约10倍。因此，MIC测试无法预测4 - 喹诺酮类药物对铜绿假单胞菌的相对杀菌效力。所以，MIC测试不应像通常那样用作4 - 喹诺酮类药物疗效的唯一衡量标准。令人惊讶的是，在测试铜绿假单胞菌时，通常4 - 喹诺酮类药物对其他细菌所呈现的典型双相剂量反应曲线并不存在。这种不寻常的效应可通过在高4 - 喹诺酮浓度下与独特的杀菌机制A丧失相关的杀菌机制B的存在来解释。杀菌机制A的丧失可能解释了近期铜绿假单胞菌染色体介导的4 - 喹诺酮耐药性的高发生率，因为铜绿假单胞菌突变以抵抗一种作用机制可能比突变以抵抗两种或更多种作用机制更容易。
