Hori S, Ohshita Y, Utsui Y, Hiramatsu K
Department of Bacteriology, Juntendo University, Tokyo, Japan.
Antimicrob Agents Chemother. 1993 Nov;37(11):2278-84. doi: 10.1128/AAC.37.11.2278.
The acquisition of ofloxacin resistance by a susceptible clinical Staphylococcus aureus strain was found to be achieved in two sequential steps: the first step was accompanied by 4-fold increases in the ofloxacin MIC and 8- to 16-fold increases in the norfloxacin MIC. The second step was accompanied by further increases in both the ofloxacin and the norfloxacin MICs. A mutation of the gyrA gene resulting in an amino acid substitution was found in the second-step but not in the first-step resistant subclone. On the other hand, there was no difference in the accumulation of norfloxacin in the parent strain and the resistant subclones of each step. The rates of mutation to resistance in the steps were (1.58 to 6.81) x 10(-9) and (0.71 to 2.59) x 10(-9), respectively, and did not depend on whether the parent strain was resistant to methicillin. Some implications of these observations for clinical as well as mechanistic aspects of the prevalence of methicillin- and ofloxacin-resistant S. aureus are discussed.
研究发现，一株敏感的临床金黄色葡萄球菌菌株获得对氧氟沙星的耐药性需经过两个连续步骤：第一步，氧氟沙星的最低抑菌浓度（MIC）增加4倍，诺氟沙星的MIC增加8至16倍。第二步，氧氟沙星和诺氟沙星的MIC进一步增加。在第二步耐药亚克隆中发现了导致氨基酸替换的gyrA基因突变，但在第一步耐药亚克隆中未发现。另一方面，亲代菌株以及各步骤耐药亚克隆中诺氟沙星的蓄积没有差异。各步骤中耐药突变率分别为(1.58至6.81)×10⁻⁹和(0.71至2.59)×10⁻⁹，且不取决于亲代菌株是否对甲氧西林耐药。本文讨论了这些观察结果对耐甲氧西林和耐氧氟沙星金黄色葡萄球菌流行的临床及机制方面的一些启示。
