Is ‘dosing-to-cure’ appropriate in the face of antimicrobial resistance?

In vitro studies have defined antimicrobial concentration ranges within which resistant bacterial mutants are enriched. Each pathogen–antimicrobial combination has a characteristic range called the mutant selection window. Traditional antimicrobial dosing strategies, which are designed to cure disease, tend to place drug concentrations inside selection windows. Removal of resistant mutant subpopulations then relies on the action of host defences rather than antimicrobial treatment. Such strategies will lead increasingly to antimicrobial resistance because immunosuppression is becoming more widespread. Alternative approaches for closing the selection window and for keeping antimicrobial concentrations outside the window are discussed.