Optimizing dosage to prevent emergence of resistance – lessons from in vitro models

The widespread emergence of resistance to antimicrobial agents has taken mammoth dimension and warrants immediate steps to minimize it. Pharmacokinetics/pharmacodynamics of antimicrobial agents, differences among bacterial species, and time-dependent changes in the bacterial population are important factors involved in the development of drug resistance. The key to minimizing resistance lies in understanding how these factors affect resistance emergence and incorporating them in dosing regimen design. In vitro models have proven to be a valuable tool to study these factors and their contribution in resistance emergence. This review summarizes the key factors implicated in resistance development and the lessons learnt from in vitro studies optimizing antimicrobial dosing to prevent resistance emergence.

► The historic approach to antimicrobial dosing focused on clinical efficacy.
► We reviewed the relevant literature regarding antimicrobial dosing optimization.
► Emphasis was placed to prevent resistance emergence using in vitro models.
► The impact of various drug, bacteria and time-related factors were discussed.
► Compared to clinical cure, prevention of resistance emergence often needs higher doses.