The ongoing global rise of antimicrobial-resistance (AMR) is forcing healthcare to rely more frequently on ‘last-resort’ antibiotics with higher risks for patients. The polymyxins are among the most prevalent last resort antibiotics as they are increasing used for the treatment of infections caused by multi drug resistant Gram-negative pathogens. A range of acute toxicities are linked to polymyxin treatment, most notably dose limiting nephrotoxicity, which requires a careful balance between the dose required for efficacy while minimizing toxicity. In Project PRADA we will pursue an innovative solution to address the inherent toxicity associated with the polymyxin family of antibiotics. We will do so by further investigating the clinical potential of a new class of polymyxins recently discovered in our labs in Leiden. These next-generation polymyxins maintain potent antibacterial activity and have a significantly improved safety profile (i.e., reduced nephrotoxicity).
