Antibiotic Synergy Definition and Quantification

Core Concept

• The European Society of Clinical Microbiology and Infectious Diseases defines antibiotic synergy as the combined effect of two or more antimicrobial agents exceeding the additive effects of the individual components when used alone 1, 2, 3
• Synergistic action is present when the antimicrobial effect of a combination is greater than simply adding together the effects of each drug individually, differing from additive effects or indifference 1
• This concept differs fundamentally from an additive effect, where the combination equals the sum of individual effects, or indifference, where the combination equals only the most active component 1, 2

Mathematical Quantification

• The European Society of Clinical Microbiology and Infectious Diseases defines synergy using the Fractional Inhibitory Concentration (FIC) Index 1, 2, 3
• For two antibiotics A and B, the FIC Index (ΣFIC) is calculated as FICA + FICB, where FICA = (MICA in presence of B) / (MICA alone) and FICB = (MICB in presence of A) / (MICB alone) 1, 2, 3
• Synergy is typically defined as ΣFIC ≤ 0.5, though specific threshold criteria are provided in standardized tables 1

Clinical Context and Important Caveats

• These synergistic effects are demonstrated in vitro, and their clinical significance remains unclear 1, 3
• Clinical studies are needed to determine the therapeutic responses of synergistic combinations in severe infections 1, 3
• Alternative testing methods, such as time-kill curves, isobologram analysis, and Fractional Bactericidal Concentration (FBC), can demonstrate synergy beyond FIC calculations 1, 3