Lambert R J W, Hanlon G W, Denyer S P
R2-Scientific, Bedfordshire, UK.
J Appl Microbiol. 2004;96(2):244-53. doi: 10.1046/j.1365-2672.2004.02135.x.
To demonstrate that the nonlinear concentration-dependent inhibition of Pseudomonas aeruginosa to EDTA can be used to successfully model and predict the potentiation of antimicrobials by EDTA.
A model used successfully to describe the concentration-dependent inhibition of bacterial growth caused by many antimicrobials was unable to describe the inhibition of P. aeruginosa by EDTA. Examination of the inhibition profiles for EDTA against P. aeruginosa revealed a biphasic inhibitory pattern suggesting different mechanisms of action at different concentrations. A modelled, two-stage inhibitory process was shown to fit the observations. This model was then used to examine the effect of combining EDTA with other antimicrobials. The apparent synergy of mixtures of EDTA with quaternary ammonium surfactants (QAC) and specific antibiotics was successfully modelled. Minimum inhibitory concentrations (MIC) of the QAC and that of oxacillin and cefamandole were reduced by a factor of 3-10, whereas ampicillin was reduced by a factor of 70 from an MIC of 1524 to 21 mg l(-1) in the presence of 500 mg l(-1) of EDTA.
A nonlinear concentration-dependent inhibition of P. aeruginosa by EDTA gives rise to apparent observation of synergy with other antimicrobials.
This is a further example where the current methodology for the examination of antimicrobial synergy (the summed fractional inhibitory concentrations) leads to false conclusions.
证明铜绿假单胞菌对乙二胺四乙酸（EDTA）的非线性浓度依赖性抑制可用于成功模拟和预测EDTA对抗菌药物的增效作用。
一个成功用于描述多种抗菌药物引起的细菌生长浓度依赖性抑制的模型，无法描述EDTA对铜绿假单胞菌的抑制作用。对EDTA针对铜绿假单胞菌的抑制曲线进行检查，发现呈双相抑制模式，表明在不同浓度下有不同的作用机制。结果显示一个模拟的两阶段抑制过程符合观察结果。然后使用该模型研究EDTA与其他抗菌药物联合使用的效果。成功模拟了EDTA与季铵表面活性剂（QAC）和特定抗生素混合物的明显协同作用。在存在500mg/L EDTA的情况下，QAC以及苯唑西林和头孢孟多的最低抑菌浓度（MIC）降低了3至10倍，而氨苄西林的MIC从1524mg/L降至21mg/L，降低了70倍。
EDTA对铜绿假单胞菌的非线性浓度依赖性抑制导致与其他抗菌药物产生明显的协同作用。
这是当前抗菌协同作用检测方法（累积分数抑菌浓度）导致错误结论的又一个例子。
