Enhanced Antimicrobial and Antiseptic Effects of Polyethylene Glycol –Citric Acid Hyperbranched Polymer‐Antibiotic Combinations against Multidrug‐Resistant Natural Isolates

Abstract Our primary motivation stems from the success of antibiotics in combating infectious diseases, which has profoundly influenced human society. However, it has also led to the emergence of multidrug‐resistant (MDR) bacterial strains, posing significant challenges to global health. These pathogens driven by the overuse and misuse of antibiotics have developed mechanisms such as enzymatic degradation, target modification, and efflux pumps to resist traditional treatments. In this context, hyperbranched polymers (HBPs) offer a promising alternative due to their unique branched structure and customizable properties, which can disrupt bacterial membranes and inhibit biofilm formation. Thus, with this backdrop this study explores the synergistic effects of polyethylene glycol (PEG) and citric acid‐based HBPs in combination with the aminoglycoside antibiotic streptomycin against MDR bacteria. Utilizing cup‐plate assays, growth curve analysis, UV–vis spectroscopy, DNA gel electrophoresis, septicemia tests, and in silico molecular docking, we demonstrate the enhanced antimicrobial efficacy of these combinations. Our findings suggest that HBPs can significantly boost antibiotic effectiveness, delay resistance development, and provide a novel approach to treating MDR infections. The PEG‐citric acid HBPs, particularly in 1:5 (S4) and 1:6 (S5) ratios, exhibit notable potential in synergistic therapy, offering a valuable tool in the fight against resistant bacterial pathogens.