The mutant selection window and antimicrobial resistance

Abstract

The mutant selection window is an antimicrobial concentration range extending from the minimal concentration required to block the growth of wild-type bacteria up to that required to inhibit the growth of the least susceptible, single-step mutant. The upper boundary is also called the mutant prevention concentration (MPC). Placing antimicrobial concentrations inside the window is expected to enrich resistant mutant subpopulations selectively, whereas placing concentrations above the window is expected to restrict selective enrichment. Since window dimensions are characteristic of each pathogen-antimicrobial combination, they can be linked with antimicrobial pharmacokinetics to rank compounds and dosing regimens in terms of their propensity to enrich mutant fractions of bacterial populations. For situations in which antimicrobial concentrations cannot be kept above the window, restricting the enrichment of mutants requires combination therapy.