Optimizing drug exposure to minimize selection of antibiotic resistance

Abstract

The worldwide increase in antibiotic resistance is a concern for public health. The fact that the choice of dose and treatment duration can affect the selection of antibiotic-resistant mutants is becoming more evident, and an increased number of studies have used pharmacodynamic models to describe the drug exposure and pharmacodynamic breakpoints needed to minimize and predict the development of resistance. However, there remains a lack of sufficient data, and future work is needed to fully characterize these target drug concentrations. More knowledge is also needed of drug pharmacodynamics versus bacteria with different resistance mutations and susceptibility levels. The dosing regimens should exhibit high efficacy not only against susceptible wild-type bacteria but, preferably, also against mutated bacteria that may exist in low numbers in "susceptible" populations. Thus, to prolong the life span of existing and new antibiotics, it is important that dosing regimens be carefully selected on the basis of pharmacokinetic and pharmacodynamic properties that prevent emergence of preexisting and newly formed mutants.