Combating Concomitant Bacterial and Fungal Infections via Codelivery of Nitric Oxide and Fluconazole

Device-associated infections are a major challenge for healthcare and cause patient morbidity and mortality as well as pose a significant economic burden. Infection-causing bacteria and fungi are equally notorious and responsible for biofilm formation and the development of antibiotic and antifungal-resistant strains. Biomaterials resisting bacterial and fungal adhesion can address device-associated infections more safely and efficiently than conventional systemic antibiotic therapies. Herein, we present a combination of potent antibacterial nitric oxide (NO) with antifungal fluconazole codelivery system from a polymeric matrix to combat bacterial and fungal infections simultaneously. The NO donor <i>S</i>-nitroso-<i>N</i>-acetyl-penicillamine (SNAP)-blended low-water-uptake polycarbonate urethane (TSPCU) was dip-coated with high-water-uptake polyether urethane (TPU) containing fluconazole to have an antibacterial and antifungal surface. The composites were characterized for surface wettability and coating stability using water contact angle (WCA) analysis. The real-time NO release (72 h) was evaluated using a chemiluminescence-based nitric oxide analyzer which showed physiologically relevant levels of NO released. The composites released fluconazole for 72 h under physiological conditions. Antibacterial analysis demonstrated a > 3-log reduction of viable <i>Staphylococcus aureus</i> and >2-log reduction of viable <i>Escherichia coli</i> compared to controls. The antifungal evaluation resulted in ∼98% reduction in adhered and ∼92% reduction in planktonic <i>Candida albicans</i>. The SNAP-fluconazole composites also showed biocompatibility against mouse fibroblast cells. This novel preventative strategy to combat bacterial and fungal infections may offer a promising tool for further translational research.