Evolution of antibiotic resistance at low antibiotic concentrations including selection below the minimal selective concentration

Stanton et al. determine the minimal selective concentrations for macrolide and fluoroquinolone antibiotics and describe a selective window defined by the minimal increased persistence concentration. These assessments and thresholds allow for better assessment of potential selection for antibiotic resistance and the risks of human exposure and environmental transmission. Determining the selective potential of antibiotics at environmental concentrations is critical for designing effective strategies to limit selection for antibiotic resistance. This study determined the minimal selective concentrations (MSCs) for macrolide and fluoroquinolone antibiotics included on the European Commission & apos;s Water Framework Directive's priority hazardous substances Watch List. The macrolides demonstrated positive selection forermFat concentrations 1-2 orders of magnitude greater (>500 and <750 mu g/L) than measured environmental concentrations (MECs). Ciprofloxacin illustrated positive selection forintI1at concentrations similar to current MECs (>7.8 and <15.6 mu g/L). This highlights the need for compound specific assessment of selective potential. In addition, a sub-MSC selective window defined by the minimal increased persistence concentration (MIPC) is described. Differential rates of negative selection (or persistence) were associated with elevated prevalence relative to the no antibiotic control below the MSC. This increased persistence leads to opportunities for further selection over time and risk of human exposure and environmental transmission.