Adapting to Drug Resistance

摘要

Developing a new therapy for drug-resistant infections is an expensive and arduous process that may give relief for less time that it takes to develop the agent. Hence, delaying the onset of resistance by administering drugs in combination is a currently favored strategy, but two groups show this may not be quite so simple to implement wisely. By experimentation and modeling, Hegreness et al. made the counterintuitive discovery that synergistically acting drug pairs, such as doxycycline and erythromycin, may actually accelerate the evolution of resistance. In fact, antagonistic drug pairs are more effective at forestalling resistance emergence because as one drug becomes ineffective, its suppressive effect on the other diminishes and unmasks the potency of the second drug. Of course, the precise outcome depends on the drug ratios, doses, pharmacokinetics, and modes of action.