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Placing MIC near the lower
boundary of the selection window contradicts traditional medical teaching in which
resistant mutants are thought to be selected primarily when drug concentrations are below
MIC (shown in a figure taken from a book published in 2002 (2)). This distinction is
important because traditional dosing recommendations to exceed MIC are likely to place
drug concentrations inside the selection window where they will enrich resistant mutant
subpopulations. While low drug concentrations do not enrich resistant mutants, they do
allow pathogen population expansion; consequently, low drug doses indirectly foster the
generation of new mutants that will be enriched by subsequent antimicrobial challenge. |