Time for precision: A world without susceptibility breakpoints

Abstract

Interpretive criteria for in vitro susceptibility testing criteria, “susceptibility breakpoints,” underpin the evaluation and selection of antimicrobial regimens. However, despite their strengths, susceptibility breakpoints are a relatively blunt instrument employed to address an extremely complex question-what is the likelihood of treatment success for individual patients? With regard to evaluating patients on a case-by-case basis, breakpoints merely allow us to account for pathogen susceptibility. This approach precludes consideration of drug exposures achieved in patients, thus overlooking half of the equation for predicting treatment success. Herein, we propose the framework for considering both pathogen- and patient-specific information to provide clinicians a means of evaluating antimicrobial regimens for individual patients through tools automating pharmacokinetic-pharmacodynamic target attainment analyses. Implementing these tools along with their acceptance by professional organizations will allow for a shift in the paradigm for how antimicrobials are selected and dosed-toward patient-centered care through precision medicine.