A Macromolecule Reversing Antibiotic Resistance Phenotype and Repurposing Drugs as Potent Antibiotics

In order to mitigate Antibiotic resistance, a new strategy to increase Antibiotic potency and reverse drug resistance is needed. Herein, the translocation mechanism of an antimicrobial guanidinium-functionalized polycarbonate is leveraged in combination with traditional Antibiotics to afford a potent treatment for drug-resistant bacteria. Particularly, this polymer-antibiotic combination approach reverses rifampicin resistance phenotype in Acinetobacter baumannii demonstrating a 2.5 × 10⁵-fold reduction in minimum inhibitory concentration (MIC) and a 4096-fold reduction in minimum bactericidal concentration (MBC). This approach also enables the repurposing of auranofin as an Antibiotic against multidrug-resistant (MDR) Gram-negative bacteria with a 512-fold MIC and 128-fold MBC reduction, respectively. 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 phenotype and repurposing drugs against MDR Gram-negative bacteria.