A method for testing for synergy with any number of agents

Area of Science:

• Microbiology
• Pharmacology
• Computational Biology

Background:

• Standard checkerboard titration is limited to 2-antibiotic synergy testing.
• Testing combinations of 3+ antibiotics is laborious and not feasible.
• Effective multi-drug combinations are crucial for treating resistant infections.

Purpose of the Study:

• To develop a simplified method for measuring synergy/antagonism in combinations of any number of agents.
• To provide a more feasible approach than standard checkerboard titrations for multi-drug testing.

Main Methods:

• Determined concentrations of n agents yielding a specific effect (e.g., MIC, MBC).
• Titrated a reference combination (1/n of each agent's concentration).
• Calculated synergy/antagonism based on the dilution factor, equivalent to the sum of fractional inhibitory concentrations (FICs).

Main Results:

• The new method is less laborious than standard checkerboard titrations for 2 agents.
• The dilution factor directly correlates with the sum of FICs.
• Sums < 1, = 1, and > 1 indicate synergy, additivity, and antagonism, respectively.

Conclusions:

• A simple, efficient method for assessing multi-agent synergy/antagonism has been developed.
• This method overcomes the limitations of checkerboard titrations for combinations of 4+ agents.
• Facilitates discovery of superior antibiotic combinations for combating resistant infections.