Antibiotic/Macromolecule Combination Reverses Antibiotic Resistance and Promotes Synergy

In order to mitigate antibiotic resistance, a new strategy to increase antibiotic potency and reverse drug resistance is needed. Here, we leverage the translocation mechanism of an antimicrobial guanidinium-functionalized polycarbonate in combination with traditional antibiotics to afford a strong synergistic treatment for drug-resistant bacteria. This polymer-antibiotic combination approach reverses rifampicin resistance in A. baumannii demonstrating a 2.5×105 folds reduction in MIC. This approach also enables the repurposing of auranofin as antibiotic against multidrug-resistant (MDR) Gram-negative bacteria with a 500-fold MIC reduction. Finally, the in vivo efficacy of polymer-rifampicin combination is demonstrated in a MDR bacteremia mouse model. This combination approach lays foundational ground rules for a new class of antibiotic adjuvants capable of reversing drug resistance and enhancing potency of common antibiotics against MDR bacteria.