Title : Quadruple Checkerboard: A modification of the three dimensional checkerboard for studying drugs combinations
Abstract:
Since the discovery of antimicrobial agents, their use had increased in the medical field and expanded to other fields. This caused the development of the “shadow epidemic”. Antimicrobial resistance caused by the misuse and overuse of antimicrobial drugs resulted in a crisis that needs to be solved. Drug combination is one of the solutions that can help in decreasing and controlling the development of resistance. The concept of combining drugs as a treatment for several diseases showed good results and promising control for the misuse of these drugs. Drugs acting synergistically in a combination given as treatment showed positive results and can be explained by several principles (collateral sensitivity,…) Several methods were developed and used to test for drug combination options, however, none of the methods was declared to be the gold standard. The methods used can test for all possible combinations obtained by combining 2 drugs (checkerboard, combined E-test, Time Kill Curve assay) and by combining 3 drugs (three dimensional checkerboard and Time kill curve assay). Only the Time kill curve assay can test for the combination of 4 drugs. However, this method is time consuming and requires a lot of labor work to conduct it. Thus, Quadruple checkerboard also called Q-checkerboard was developed. This new modified technique can study all possible combinations that can be obtained by combining 4 drugs in one single experiment. It is time saving and requires less labor work. The experimental steps will be discussed highlighting the crucial steps needed to perform this technique. In addition to the experimental protocol, an FIC sheet will be also discussed which was developed using excel in order to visualize easily the results with a minimum amount of work. The FIC criteria used to assess synergy, antagonism and indifference is not standard where we can see in literature the difference in the values used for synergy and antagonism. For the Q-checkerboard, several modifications were taken into consideration regarding the FIC value and how to obtain it. These modifications will be discussed in the presentation explaining the idea behind doing such changes.
What will audience learn from your presentation?
- Learning such technique, will give researchers a deeper idea about it which will be useful if they want to engage such technique in their research experiments.
- Discussing this technique will open doors to further discussions about FIC interpretation that should be highlighted regarding the big dilemma about the interpretation values.
- As for the technical part of this technique, it opens door for biomedical testing companies and other companies to manufacture a better suiting plates and other equipment according to the developed experimental conditions.
