Synergistic antibacterial activity of norfloxacin and sulfadiazine against planktonic and biofilm-forming multidrug-resistant <i>Escherichia coli</i> strain

Antimicrobial resistance represents a major global health concern, particularly in countries where multidrug-resistant (MDR) pathogens are widespread. Biofilm formation further complicates therapeutic strategies. This study investigated the synergistic effects of combining norfloxacin (NOR) and sulfadiazine (SDZ) against three Escherichia coli strains: a reference, a quinolone-resistant clinical isolate, and a highly resistant extended-spectrum β-lactamase (ESBL)-producing strain. Checkerboard assays and isobolograms revealed synergistic or partially synergistic effects across all strains, with Fractional Inhibitory Concentration Index (FICI) values ranging from 0.37 to 1.0. Notably, the ESBL strain displayed enhanced synergy (FICI = 0.75) under white LED light irradiation. Reactive oxygen species (ROS) analysis showed that SDZ generated higher levels than NOR, particularly in the quinolone-resistant clinical isolate, while the NOR-SDZ combination yielded lower levels. Scanning electron microscopy of biofilms confirmed that the drug combination caused greater structural disruption than either monotherapy, especially at NOR (FIC × 100) and SDZ (FIC × 10). Subinhibitory monotherapies modulated the biofilm phenotype, underscoring the benefits of combined treatments. Overall, these findings highlight the NOR-SDZ combination as a promising therapeutic approach against MDR E. coli, where drug synergy and biofilm disruption emerge as key strategies to combat antimicrobial resistance.