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This study determined the minimal selective concentrations (MSCs) for macrolide and fluoroquinolone antibiotics included on the European Commission\u02bcs Water Framework Directive\u2019s priority hazardous substances\u00a0Watch List. The macrolides demonstrated positive selection for <jats:italic>ermF<\/jats:italic> at concentrations 1\u20132 orders of magnitude greater (&gt;500 and &lt;750\u2009\u00b5g\/L) than measured environmental concentrations (MECs). Ciprofloxacin illustrated positive selection for <jats:italic>intI1<\/jats:italic> at concentrations similar to current MECs (&gt;7.8 and &lt;15.6\u2009\u00b5g\/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. 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