Synergistic antibacterial and anti-biofilm activities of resveratrol and polymyxin B against multidrug-resistant Pseudomonas aeruginosa

Bacterial infection caused by multidrug-resistant Pseudomonas aeruginosa has become a challenge in clinical practice. Polymyxins are used as the last resort agent for otherwise untreatable Gram-negative bacteria, including multidrug-resistant P.aeruginosa. However, pharmacodynamic (PD) and pharmacokinetic (PK) data on polymyxins suggest that polymyxin monotherapy is unlikely to generate reliably efficacious plasma concentrations. Also, polymyxin resistance has been frequently reported, especially among multidrug-resistant P.aeruginosa, which further limits its clinical use. A strategy for improving the antibacterial activity of polymyxins and preventing the development of polymyxin resistance is to use polymyxins in combination with other agents. In this study, we have demonstrated that resveratrol, a well tolerated compound, has synergistic effects when tested in vitro with polymyxin B on antibacterial and anti-biofilm activities. However, its' systemic use is limited as the required high plasma levels of resveratrol are not achievable. This suggests that it could be a partner for the combination therapy of polymyxin B in the treatment of topical bacterial infection caused by MDR P.aeruginosa.