Influence of rhlR and lasR on Polymyxin Pharmacodynamics in Pseudomonas aeruginosa and Implications for Quorum Sensing Inhibition with Azithromycin

Abstract

ABSTRACT The impact of quorum sensing on polymyxin and azithromycin pharmacodynamics was assessed in Pseudomonas aeruginosa PAO1 and an isogenic rhlR / lasR double knockout. For polymyxin B, greater killing against the rhlR / lasR knockout than against PAO1 was observed at 10 8 CFU/ml (polymyxin B half-maximal effective concentration [EC 50 ], 5.61 versus 12.5 mg/liter, respectively; P < 0.005). Polymyxin B combined with azithromycin (256 mg/liter) was synergistic against each strain, significantly reducing the respective polymyxin B EC 50 compared to those with monotherapy ( P < 0.005), and is a promising strategy by which to combat P. aeruginosa .