Antibiotic resistance—What’s dosing got to do with it?

Abstract

OBJECTIVE: This review seeks to identify original research articles that link antibiotic dosing and the development of antibiotic resistance for different antibiotic classes. Using this data, we seek to apply pharmacodynamic principles to assist clinical practice for suppressing the emergence of resistance. Concepts such as mutant selection window and mutant prevention concentration will be discussed. DATA SOURCES: PubMed, EMBASE, and the Cochrane Controlled Trial Register. STUDY SELECTION: All articles that related antibiotic doses and exposure to the formation of antibiotic resistance were reviewed. DATA SYNTHESIS: The escalation of antibiotic resistance continues worldwide, most prominently in patients in intensive care units. Data are emerging from in vitro and in vivo studies that suggest that inappropriately low antibiotic dosing may be contributing to the increasing rate of antibiotic resistance. Fluoroquinolones have widely been researched and publications on other antibiotic classes are emerging. Developing dosing regimens that adhere to pharmacodynamic principles and maximize antibiotic exposure is essential to reduce the increasing rate of antibiotic resistance. CONCLUSIONS: Antibiotic dosing must aim to address not only the bacteria isolated, but also the most resistant subpopulation in the colony, to prevent the advent of further resistant infections because of the inadvertent selection pressure of current dosing regimens. This may be achieved by maximizing antibiotic exposure by administering the highest recommended dose to the patient.