Adapting to Drug Resistance

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Science  03 Oct 2008:
Vol. 322, Issue 5898, pp. 16
DOI: 10.1126/science.322.5898.16b

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.

Developing policies for the implementation of drug combinations requires population modeling. Boni et al. compared the consequences of the standard wait-and-switch global deployment of drugs for malaria control with the simultaneous deployment of multiple drugs. Their model shows that if three different drugs are offered for use at the same time within a malarious population, the clinical burden is reduced, the emergence of resistance is delayed by two- to fourfold, and the number of failed treatments is almost halved. — CA

Proc. Natl. Acad. Sci. U.S.A. 105, 13977, 14216 (2008).

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