In a checkerboard broth microdilution assay combining drug X and drug Y against a Klebsiella pneumoniae isolate, the MIC of drug X alone is 4 mg/L and falls to 1 mg/L in combination; the MIC of drug Y alone is 8 mg/L and falls to 2 mg/L in combination. The fractional inhibitory concentration (FIC) index is therefore 0.5. This result is interpreted as:

• A Antagonism
• B Indifference
• C Additivity only if both drugs share the same target
• D Synergy ✓

Explanation

The FIC index equals the sum of the fractional MICs in combination, here 1/4 plus 2/8, giving 0.5. By conventional criteria a FIC index of 0.5 or less denotes synergy, values above 0.5 up to 1 indicate additivity or indifference, and values above 4 indicate antagonism. Shared targets are not required for synergy; indeed many synergistic pairs act on different pathways, such as a cell-wall agent with an aminoglycoside. Antagonism would require a markedly higher index than 0.5.

Reference: Koneman's Color Atlas and Textbook of Diagnostic Microbiology, 7th ed.

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