Antibiotic Synergism Requires Simultaneous Presence of Both Members of a Synergistic Drug Pair.

(1) It has been demonstrated in two systems that antibiotic synergism is observed only when both members of a synergistic pair of drugs are acting simultaneously on the bacterial population, not when they act in sequence. It may, therefore, be suggested that antibiotic synergism is not usually the result of a modification in a bacterial population induced by one drug, which renders the microorganisms more susceptible to the other drug of a synergistic pair. (2) These findings would tend to favor a hypothesis of synergism involving simultaneous blocking of alternate enzymatic pathways.