Gwynn M N, Rolinson G N
Infection. 1980;8(2):73-80. doi: 10.1007/BF01639151.
In broth cultures of Pseudomonas aeruginosa, containing carbenicillin or azlocillin, regrowth occurred after a period of bactericidal action, to reach visible proportions overnight. Regrowth in the presence of relatively high concentrations of carbenicillin or azlocillin could not be accounted for on the basis of growth of resistant variants nor as a result of drug inactivation. On the other hand, resistant variants could be selected from the regrowth which occurred at concentrations of carbenicillin or azlocillin only slight in excess of the minimum inhibitory concentrations (MIC). Antibiotic resistant variants could also be isolated from individual colonies growing on agar plates containing carbenicillin, ticarcillin, azlocillin or piperaccillin at concentrations above the MIC for the majority of the population. Two types of resistant variant were isolated. The first showed a 2-5 fold increase in resistance to carbenicillin, ticarcillin, azlocillin and piperacillin while Beta-lactamase production in these variants appeared to be unchanged. The second type of resistant variant showed unchanged sensitivity to carbenicillin and ticarcillin, or only a slight increase in resistance, whereas resistance to azlocillin and piperacillin was increased as much as 40-fold or more. These variants showed increased constitutive Beta-lactamase production and may be derepressed mutants of the parent culture. Variants of this type were readily selected by culture in the presence of azlocillin or piperacillin but only infrequently as a result of culture in the presence of carbenicillin or ticarcillin. The existence in cultures of P. aeruginosa of variants showing elevated Beta-lactamase production may account at least in part for the effect of inoculum size on the activity of azlocillin and piperacillin against P. aeruginosa and the marked discrepancy between MIC and minimum bactericidal concentration (MBC) which is characteristic of the ureido penicillins.
在含有羧苄西林或阿洛西林的铜绿假单胞菌肉汤培养物中，经过一段时间的杀菌作用后会出现再生长现象，过夜后达到可见数量。在相对高浓度的羧苄西林或阿洛西林存在下的再生长，既不能用耐药变体的生长来解释，也不是药物失活的结果。另一方面，在羧苄西林或阿洛西林浓度仅略高于最低抑菌浓度（MIC）时出现的再生长中，可以筛选出耐药变体。在含有高于大多数群体MIC浓度的羧苄西林、替卡西林、阿洛西林或哌拉西林的琼脂平板上生长的单个菌落中，也可以分离出抗生素耐药变体。分离出了两种类型的耐药变体。第一种对羧苄西林、替卡西林、阿洛西林和哌拉西林的耐药性增加了2至5倍，而这些变体中的β-内酰胺酶产生似乎未发生变化。第二种耐药变体对羧苄西林和替卡西林的敏感性未变，或仅耐药性略有增加，而对阿洛西林和哌拉西林的耐药性增加了多达40倍或更多。这些变体显示组成型β-内酰胺酶产生增加，可能是亲本培养物的去阻遏突变体。这种类型的变体很容易在阿洛西林或哌拉西林存在下通过培养筛选出来，但在羧苄西林或替卡西林存在下培养时很少出现。铜绿假单胞菌培养物中存在β-内酰胺酶产生增加的变体，这可能至少部分解释了接种量对阿洛西林和哌拉西林抗铜绿假单胞菌活性的影响，以及脲基青霉素特有的MIC和最低杀菌浓度（MBC）之间的显著差异。
