Cationic Antimicrobial Carbon Acid Polymer Eradicates <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Biofilms

Biofilm-associated infections exhibit high tolerance to antibiotics and antimicrobials, posing a significant challenge to wound management. <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> are among the most prevalent pathogens in biofilm-associated wound infections. Here, we report a main-chain cationic antimicrobial polymer, poly(butylimidazolium) (PIM1), whose imidazolium units feature an acidic C2-H carbon center. PIM1 demonstrated potent broad-spectrum activity against multidrug-resistant (MDR) bacteria with minimal cytotoxicity toward multiple mammalian cell lines in vitro. PIM1 retained fast bactericidal activity under physiological conditions, including whole blood and high bacterial inoculum. Interestingly, its potency increased 2- to 4-fold in the presence of serum. PIM1 also eliminated antibiotic-tolerant persister cells and eradicated biofilms formed by MDR pathogens. In vivo, 7-day continuous topical administration of PIM1 on murine wounds caused no observable toxicity. In murine excisional wound infection models, topical PIM1 treatment achieved >99% eradication of <i>P. aeruginosa</i> and <i>S. aureus</i> biofilms, outperforming imipenem and vancomycin controls, respectively. These findings support PIM1 as a safe and effective therapeutic candidate for treating biofilm-associated wound infections caused by MDR bacteria.