Lambert R J W, Lambert R
R2-Scientific, Sharnbrook, Bedfordshire, UK.
J Appl Microbiol. 2003;95(4):734-43. doi: 10.1046/j.1365-2672.2003.02039.x.
The method of the sum of the fractional inhibitory concentrations (SigmaFIC) is used ubiquitously in the investigation of antimicrobial combinations. The inherent assumption of this simple equation is that in a mixture all antimicrobials have identical dose responses. The aim of this work was to analyse the outcome of removing this assumption.
A model to describe the efficacy of combined inhibitors was produced which removed the assumption of identical dose responses. The results of several checkerboard experiments showed that the new model, termed the facomb was a more general form of the SigmaFIC method, but the features described by the SigmaFIC as either synergy or antagonism could be attributed to differences in the dose responses of antimicrobials in combination. Where the model failed to adequately describe experimental data it was suggested that these might be cases of true antagonism or synergy.
The SigmaFIC methodology used to describe the effect of antimicrobial combinations (preservatives and antibiotics) is valid only when it is demonstrated that individual components of the mixture have identical dose responses. Otherwise the SigmaFIC method is invalid. Descriptions of antimicrobial synergy may simply be due to the mixing of antimicrobials with differing dose responses.
Studies aimed at producing synergistic mixtures of antimicrobials, which ignore the dose response of the individual antimicrobials, may waste valuable research effort looking for a physiological explanation for an apparent synergy, where none, in-fact, exists. Conversely, mixing antimicrobials with very different dose responses might lead to mixtures with an 'apparent' synergy which may themselves be very useful therapeutically.
分数抑制浓度总和（SigmaFIC）方法在抗菌药物联合研究中被广泛使用。这个简单公式的内在假设是，在混合物中所有抗菌药物具有相同的剂量反应。本研究的目的是分析去除该假设后的结果。
建立了一个描述联合抑制剂疗效的模型，该模型去除了相同剂量反应的假设。多个棋盘实验结果表明，新模型（称为facomb）是SigmaFIC方法的更通用形式，但SigmaFIC所描述的协同或拮抗特征可能归因于联合使用的抗菌药物剂量反应的差异。当该模型未能充分描述实验数据时，提示这些可能是真正的拮抗或协同情况。
用于描述抗菌药物联合（防腐剂和抗生素）作用的SigmaFIC方法仅在证明混合物的各个成分具有相同剂量反应时才有效。否则，SigmaFIC方法无效。抗菌协同作用的描述可能仅仅是由于具有不同剂量反应的抗菌药物混合所致。
旨在产生抗菌药物协同混合物的研究，如果忽略了各个抗菌药物的剂量反应，可能会浪费宝贵的研究精力去寻找不存在的明显协同作用的生理学解释。相反，将具有非常不同剂量反应的抗菌药物混合可能会产生具有“明显”协同作用的混合物，这些混合物本身在治疗上可能非常有用。
