Wilson S G, Sanders C C
Antimicrob Agents Chemother. 1976 Sep;10(3):519-25. doi: 10.1128/AAC.10.3.519.
Susceptibility tests with aminoglycosides against Staphylococcus aureus have revealed discrepancies between the minimal inhibitory concentrations and the minimal bactericidal concentrations. To further evaluate these discrepancies, kill curves were performed against a susceptible strain of S. aureus with five different aminoglycosides (amikacin, kanamycin, tobramycin, gentamicin, sisomicin) at concentrations up to 16-fold above the minimal inhibitory concentration. Results revealed the presence of small subpopulations of cells capable of growth within 24 h in concentrations of aminoglycoside up to eightfold above the minimal inhibitory concentration for the parent strain. These subpopulations occurred at a frequency of >/=10(-7) parent cells, were not physiologically different from the susceptible parent strains, and were present in approximately one-half of 30 strains of S. aureus tested. The resistance of these subpopulations was approximately eightfold higher than that of the parent for all five aminoglycosides and was independent of concentration or type of aminoglycoside used to select them. This resistance was not due to extracellular degradation of drug and was stable over eight transfers in drug-free medium, except when selected by gentamicin or sisomicin.
用氨基糖苷类药物对金黄色葡萄球菌进行的药敏试验显示，最小抑菌浓度和最小杀菌浓度之间存在差异。为了进一步评估这些差异，针对一株对五种不同氨基糖苷类药物（阿米卡星、卡那霉素、妥布霉素、庆大霉素、西索米星）敏感的金黄色葡萄球菌菌株，在高于最小抑菌浓度16倍的浓度下绘制了杀菌曲线。结果显示，存在一小部分细胞亚群，在高于亲本菌株最小抑菌浓度八倍的氨基糖苷类药物浓度下，能够在24小时内生长。这些亚群出现的频率≥10⁻⁷个亲本细胞，与敏感亲本菌株在生理上没有差异，并且在所测试的30株金黄色葡萄球菌中约有一半存在。对于所有五种氨基糖苷类药物，这些亚群的耐药性比亲本高约八倍，并且与用于选择它们的氨基糖苷类药物的浓度或类型无关。这种耐药性不是由于药物的细胞外降解，并且在无药物培养基中传代八次后仍稳定，除了用庆大霉素或西索米星选择时。
