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The emergence of multidrug\u2010resistant Gram\u2010negative strains threatens the utility even of last resort therapeutic treatments. Significant efforts at different levels of resolution are currently focused on finding a solution to this nonpermeation problem and developing new approaches to the optimization of drug activities against multidrug\u2010resistant pathogens. The exceptional efficiency of the Gram\u2010negative permeability barrier is the result of a complex interplay between the two opposing fluxes of drugs across the two membranes. 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