Berenbaum M C
J Infect Dis. 1978 Feb;137(2):122-30. doi: 10.1093/infdis/137.2.122.
The standard checkerboard titration for detecting synergy between antibiotics is practicable for combinations of two antibiotics, laborious for combinations of three, and not feasible for combinations of four or more. Nevertheless, methods for testing of combinations of several antibiotics are urgently needed because some combinations might be superior to those in use and enable the successful treatment of infections resistant to current therapy. A simple method for measurement of synergy (or antagonism) with combinations of any number of agents has been developed which requires less effort than the standard checkerboard titration of two agents. With this method, the concentrations of each of n agents producing some specified effect (such as minimal inhibitory concentration or minimal bactericidal concentration) are determined. A reference combination made up of 1/n of each of these concentrations is titrated to find a dilution that produces the specified effect. The degree of dilution required is equal to the sum of the fractional inhibitory concentrations (concentration of each agent in combination/concentration of each agent alone) as conventionally determined by checkerboard titrations; sums of less than 1, 1, and greater than 1 indicate synergy, additivity, and antagonism, respectively.
用于检测抗生素之间协同作用的标准棋盘滴定法，对于两种抗生素的组合是可行的，对于三种抗生素的组合则很费力，而对于四种或更多种抗生素的组合则不可行。然而，迫切需要检测几种抗生素组合的方法，因为某些组合可能优于现用组合，并能成功治疗对当前治疗有抗性的感染。已经开发出一种简单的方法来测量任意数量药物组合的协同作用（或拮抗作用），该方法比两种药物的标准棋盘滴定法所需的工作量更少。使用这种方法，可以确定产生某种特定效果（如最低抑菌浓度或最低杀菌浓度）的n种药物中每种药物的浓度。将由这些浓度的1/n组成的参考组合进行滴定，以找到产生特定效果的稀释度。所需的稀释度等于通过棋盘滴定法常规确定的分数抑菌浓度（组合中每种药物的浓度/每种药物单独的浓度）之和；小于1、等于1和大于1的和分别表示协同作用、相加作用和拮抗作用。
