TABLE 1.

Consensus terminology for describing results of combination testinga

CategoryTerminology for indicated conditions
Both agents are active alone; additive effects model is presumedBoth agents are active alone; multiplicative effects model is presumedOne agent is active alone; the other is notNeither agent is active alone
Combination result is better than expectedLoewe synergismBliss synergismSynergismCoalism
Combination result is as expectedLoewe additivityBliss independenceInertismInertism
Combination result is worse than expectedLoewe antagonismBliss antagonismAntagonism
  • a The terminology shown is that proposed by Greco et al. (79) following a consensus conference occurring in Sarriselka, Finland. Models based on the additive interaction concept first proposed by Loewe and Muischnek (111) follow the intuitive result in which a drug combined with itself produces a linear sum of effects. That is, 1 μg/ml plus 1 μg/ml gives the effect of 2 μg/ml and this result is neither synergistic nor antagonistic. Models based on the multiplicative interaction concept first proposed by Bliss (26) follow a probabilistic model in which the two agents truly act independently as determined on the basis of their separate probabilities of effect. If 1 μg/ml permits 40% of the target organism to survive, then 1 + 1 = 2 μg/ml should permit only 40% × 40% = 16% survival. As reviewed in detail by Greco et al. (79), both models have strengths and weaknesses but Loewe additivity-based models more often seem appropriate for combinations of antimicrobial agents.