Inhibition of drug efflux pumps inStaphylococcus aureus: current status of potentiating existing antibiotics

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Abstract

The emergence of multidrug-resistant Staphylococcus aureus coupled with a declining output of new antibiotic treatment options from the pharmaceutical industry is a growing worldwide healthcare problem. Multidrug efflux pumps are known to play a role in antibiotic and biocide resistance in S. aureus. These membrane transporters are capable of extruding drugs and other structurally unrelated compounds, hence decreasing intracellular concentration and increasing survival. Coadministration of efflux pump inhibitors (EPIs) with antibiotics that are pump substrates could increase intracellular drug levels, thus bringing renewed efficacy to existing antistaphylococcal agents. Numerous EPIs have been identified or synthesized over the past two decades; these include existing pharmacologic drugs, naturally occurring compounds, and synthetic derivatives thereof. This review describes the current progress in EPI development for use against S. aureus.

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