UCLA

Using multiple drugs in combination has been suggested as a possible solution to the antibiotic resistance problem. However, drug combinations introduce new factors to consider, including how the interactions among drugs influence the evolutionary process. Antibiotic combinations are considered additive if the combined effect is equivalent to the drugs acting independently, synergistic if more effective and antagonistic if less effective. This study examines the evolution of S. epidermidis in single drug, two-drug, and three-drug environments to determine how the interaction types may influence the rate of adaptation. The net interaction of a combination as well as the emergent interaction—the interaction that is uniquely due to all drugs being present in a combination that is not due to pairwise interactions, was examined. We find that in three-drug combinations, synergistic net interactions correlate with higher rates of adaptation, and the emergent interaction has no significant effect on the rates of adaptation.