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Synergy assessed by checkerboard. A critical analysis
Diagnostic Microbiology and Infectious Disease
|May 1, 1993
Summary
The checkerboard dilution test for drug synergy has inherent instability due to twofold dilutions. Alternative methods show promise but also present challenges, indicating a need for improved synergy testing approaches.
Area of Science:
- Microbiology
- Pharmacology
- Drug Discovery
Background:
- The checkerboard dilution test is a standard method for assessing in vitro drug synergy.
- This method faces challenges in performance, standardization, and interpretation, particularly concerning antibiotic concentration dilutions.
Purpose of the Study:
- To evaluate an alternative checkerboard method preserving the twofold dilution scheme.
- To analyze the theoretical basis and practical implications of FIC index calculation in synergy testing.
Main Methods:
- Construction of giant checkerboards using rifampin and minocycline against Staphylococcus aureus.
- Evaluation of an alternative method proposed by Horrevorts et al. that maintained the twofold dilution scheme.
Main Results:
- The alternative method improved the stability of fractional inhibitory concentration (FIC) indices.
- However, it required substantially more labor and introduced other practical problems.
- FIC interpretation and calculation remained compromised by the inherent limitations of the twofold dilution scheme.
Conclusions:
- The twofold dilution scheme in checkerboard assays leads to inherent instability in synergy evaluation.
- While the principle of assessing combined antibiotic effects is valid, newer, more stable methods are required.